Post on 14-Mar-2020
transcript
ADVANCING INNOVATION TOWARDS BREAKTHROUGH
CANCER THERAPIES
November 2019
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions
This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and isnot to be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subjectto independent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable tocompanies listed on Euronext Paris including in particular the risk factors in the Companyrsquos latest Registration Document andor its actualization filed with the French Financial Markets Authority (Autoriteacute des marcheacutesfinanciers) in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)
This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based onthe knowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have notbeen verified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitiveposition data contained in the Information
The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution oruse would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer orthe solicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on aprospectus that complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public inthe United Kingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the USSecurities Act of 1933 as amended or an exemption from registration thereunder
This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements containedin this document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or toconfirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document
Important Information
3Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver near-term clinical inflection points
STRONG SCIENTIFIC TRANSLATIONAL amp CLINICAL CAPACITYA highly skilled amp experienced team of 35 with in-house capabilities to lead compounds from preclinical to proof-of-concept in man
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSE
PlatONtrade proprietary chemistry platform of decoy agonist oligonucleotides generatingnew compoundsAsiDNAtrade lead candidate at clinical stage first-in-class agonist showing unique anti-tumoral properties
A WELL-DEFINED BUSINESS MODELCreate value in bringing product candidates to inflection points and monetizing these assets to generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
November 2019
4
FRANCOISE BONO (PHD) CSO(Sanofi Evotec)
OLIVIER DE BEAUMONT (MD) CMO(Aventis Quintiles Stallergenes Greer)
NICOLAS FELLMAN CFO(Pfizer Ernst amp Young)
PHILIPPE MAITRE EVP CBDO(Aventis PPD mAbRx)
Experienced management team and board of directors
JUDITH GRECIETCEO
DANIEgraveLE GUYOT-CAPARROSChairperson of the Board
Chairperson of Audit committeeSenior Advisor Deloitte Consulting
CHRISTINE GARNIERCo-Founder of AEC Partners Strategic consulting
JEAN-PIERRE BIZZARIFormer EVP Clinical Oncology Celgene
THOMAS HOFSTAETTERFormer head of VaxInnate Corp
Chairman of BD committee
JEAN-PIERRE KINETImmunologist
Harvard Medical School
NICOLAS TREBOUTArepresenting Financiegravere de la Montagne
ELVIRA SANZFormer President Pfizer
Spain amp Portugal
November 2019
JUDITH GRECIET (PHARMD)CEO(formerly Pharmacia Wyeth Eisai)
5
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401Next-gen PARPi + STING pathway activation
AsiDNAtrade IT + radiotherapy
AsiDNAtrade IV
AsiDNAtrade IV + chemotherapy
AsiDNAtrade IV + PARPi
Beleodaqreg2
belinostat + platONtrade
Cutting-edge RampD pipeline with unique mechanisms of action in DDR
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS
Epig
enet
ics
DN
A D
amag
e
Re
spo
nse
1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer
4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL
DRIIM study in metastatic melanoma
2nd line PTCL3 US4
November 2019Completed or ongoing Planned short-term Legend
DD
R
+ IO
Solid tumors
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions
This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and isnot to be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subjectto independent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable tocompanies listed on Euronext Paris including in particular the risk factors in the Companyrsquos latest Registration Document andor its actualization filed with the French Financial Markets Authority (Autoriteacute des marcheacutesfinanciers) in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)
This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based onthe knowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have notbeen verified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitiveposition data contained in the Information
The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution oruse would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer orthe solicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on aprospectus that complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public inthe United Kingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the USSecurities Act of 1933 as amended or an exemption from registration thereunder
This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements containedin this document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or toconfirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document
Important Information
3Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver near-term clinical inflection points
STRONG SCIENTIFIC TRANSLATIONAL amp CLINICAL CAPACITYA highly skilled amp experienced team of 35 with in-house capabilities to lead compounds from preclinical to proof-of-concept in man
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSE
PlatONtrade proprietary chemistry platform of decoy agonist oligonucleotides generatingnew compoundsAsiDNAtrade lead candidate at clinical stage first-in-class agonist showing unique anti-tumoral properties
A WELL-DEFINED BUSINESS MODELCreate value in bringing product candidates to inflection points and monetizing these assets to generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
November 2019
4
FRANCOISE BONO (PHD) CSO(Sanofi Evotec)
OLIVIER DE BEAUMONT (MD) CMO(Aventis Quintiles Stallergenes Greer)
NICOLAS FELLMAN CFO(Pfizer Ernst amp Young)
PHILIPPE MAITRE EVP CBDO(Aventis PPD mAbRx)
Experienced management team and board of directors
JUDITH GRECIETCEO
DANIEgraveLE GUYOT-CAPARROSChairperson of the Board
Chairperson of Audit committeeSenior Advisor Deloitte Consulting
CHRISTINE GARNIERCo-Founder of AEC Partners Strategic consulting
JEAN-PIERRE BIZZARIFormer EVP Clinical Oncology Celgene
THOMAS HOFSTAETTERFormer head of VaxInnate Corp
Chairman of BD committee
JEAN-PIERRE KINETImmunologist
Harvard Medical School
NICOLAS TREBOUTArepresenting Financiegravere de la Montagne
ELVIRA SANZFormer President Pfizer
Spain amp Portugal
November 2019
JUDITH GRECIET (PHARMD)CEO(formerly Pharmacia Wyeth Eisai)
5
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401Next-gen PARPi + STING pathway activation
AsiDNAtrade IT + radiotherapy
AsiDNAtrade IV
AsiDNAtrade IV + chemotherapy
AsiDNAtrade IV + PARPi
Beleodaqreg2
belinostat + platONtrade
Cutting-edge RampD pipeline with unique mechanisms of action in DDR
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS
Epig
enet
ics
DN
A D
amag
e
Re
spo
nse
1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer
4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL
DRIIM study in metastatic melanoma
2nd line PTCL3 US4
November 2019Completed or ongoing Planned short-term Legend
DD
R
+ IO
Solid tumors
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
3Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology
NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver near-term clinical inflection points
STRONG SCIENTIFIC TRANSLATIONAL amp CLINICAL CAPACITYA highly skilled amp experienced team of 35 with in-house capabilities to lead compounds from preclinical to proof-of-concept in man
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSE
PlatONtrade proprietary chemistry platform of decoy agonist oligonucleotides generatingnew compoundsAsiDNAtrade lead candidate at clinical stage first-in-class agonist showing unique anti-tumoral properties
A WELL-DEFINED BUSINESS MODELCreate value in bringing product candidates to inflection points and monetizing these assets to generate revenues
LISTED EURONEXT Paris NASDAQ Copenhagen
EPA ONXEO
November 2019
4
FRANCOISE BONO (PHD) CSO(Sanofi Evotec)
OLIVIER DE BEAUMONT (MD) CMO(Aventis Quintiles Stallergenes Greer)
NICOLAS FELLMAN CFO(Pfizer Ernst amp Young)
PHILIPPE MAITRE EVP CBDO(Aventis PPD mAbRx)
Experienced management team and board of directors
JUDITH GRECIETCEO
DANIEgraveLE GUYOT-CAPARROSChairperson of the Board
Chairperson of Audit committeeSenior Advisor Deloitte Consulting
CHRISTINE GARNIERCo-Founder of AEC Partners Strategic consulting
JEAN-PIERRE BIZZARIFormer EVP Clinical Oncology Celgene
THOMAS HOFSTAETTERFormer head of VaxInnate Corp
Chairman of BD committee
JEAN-PIERRE KINETImmunologist
Harvard Medical School
NICOLAS TREBOUTArepresenting Financiegravere de la Montagne
ELVIRA SANZFormer President Pfizer
Spain amp Portugal
November 2019
JUDITH GRECIET (PHARMD)CEO(formerly Pharmacia Wyeth Eisai)
5
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401Next-gen PARPi + STING pathway activation
AsiDNAtrade IT + radiotherapy
AsiDNAtrade IV
AsiDNAtrade IV + chemotherapy
AsiDNAtrade IV + PARPi
Beleodaqreg2
belinostat + platONtrade
Cutting-edge RampD pipeline with unique mechanisms of action in DDR
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS
Epig
enet
ics
DN
A D
amag
e
Re
spo
nse
1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer
4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL
DRIIM study in metastatic melanoma
2nd line PTCL3 US4
November 2019Completed or ongoing Planned short-term Legend
DD
R
+ IO
Solid tumors
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
4
FRANCOISE BONO (PHD) CSO(Sanofi Evotec)
OLIVIER DE BEAUMONT (MD) CMO(Aventis Quintiles Stallergenes Greer)
NICOLAS FELLMAN CFO(Pfizer Ernst amp Young)
PHILIPPE MAITRE EVP CBDO(Aventis PPD mAbRx)
Experienced management team and board of directors
JUDITH GRECIETCEO
DANIEgraveLE GUYOT-CAPARROSChairperson of the Board
Chairperson of Audit committeeSenior Advisor Deloitte Consulting
CHRISTINE GARNIERCo-Founder of AEC Partners Strategic consulting
JEAN-PIERRE BIZZARIFormer EVP Clinical Oncology Celgene
THOMAS HOFSTAETTERFormer head of VaxInnate Corp
Chairman of BD committee
JEAN-PIERRE KINETImmunologist
Harvard Medical School
NICOLAS TREBOUTArepresenting Financiegravere de la Montagne
ELVIRA SANZFormer President Pfizer
Spain amp Portugal
November 2019
JUDITH GRECIET (PHARMD)CEO(formerly Pharmacia Wyeth Eisai)
5
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401Next-gen PARPi + STING pathway activation
AsiDNAtrade IT + radiotherapy
AsiDNAtrade IV
AsiDNAtrade IV + chemotherapy
AsiDNAtrade IV + PARPi
Beleodaqreg2
belinostat + platONtrade
Cutting-edge RampD pipeline with unique mechanisms of action in DDR
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS
Epig
enet
ics
DN
A D
amag
e
Re
spo
nse
1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer
4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL
DRIIM study in metastatic melanoma
2nd line PTCL3 US4
November 2019Completed or ongoing Planned short-term Legend
DD
R
+ IO
Solid tumors
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
5
Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET
platONtrade Proprietary Platform of Decoy Oligonucleotides
OX401Next-gen PARPi + STING pathway activation
AsiDNAtrade IT + radiotherapy
AsiDNAtrade IV
AsiDNAtrade IV + chemotherapy
AsiDNAtrade IV + PARPi
Beleodaqreg2
belinostat + platONtrade
Cutting-edge RampD pipeline with unique mechanisms of action in DDR
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS
Epig
enet
ics
DN
A D
amag
e
Re
spo
nse
1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer
4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL
DRIIM study in metastatic melanoma
2nd line PTCL3 US4
November 2019Completed or ongoing Planned short-term Legend
DD
R
+ IO
Solid tumors
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
ASIDNAtrade
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
7AsiDNAtrade is a first-in-class product in DNA Damage Response
November 2019
A synthetic cholesterol-oligonucleotide conjugate forming an intramolecular hairpin 32-base pair double helix
5rsquo
3rsquo
3rsquo
5rsquo
Genomic DNA length optimized to bind and activate DNA-PK and PARP signaling enzymes
Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1
Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1
Sequence not specific chosen to be non-homologous and not immunogenic (CpG-free)
Active 32 bp DNA duplex Cholesterol
Loop
1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113
Efficient tumoral and nuclear uptake of the DNA is mediated via a covalently linked cholesterol molecule2
Patent Protection (Composition of
Matter on AsiDNAtrade amp related compounds)
until 2031
Extendable to 2036 with SPC amp PTE
Combinationpatents up to 2038
and more
IP
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
8AsiDNAtrade is the only decoy agonist in development that disrupts and exhausts the tumor DNA Damage Response
November 2019
Actual tumor DNA damage is not repaired and accumulates cancer cells die when dividing with a damaged DNA
AsiDNAtrade is not active in healthy cells which stop dividing until the false alarm disappears
AsiDNAtrade mimics DNA breaks in the tumor cell hyperactivates and then binds the proteins needed for the DDR cascade of cellular events (sensing signaling and repairing) diverting the DDR proteins away from the true damage 123
AsiDNAtrade is a multi-target DDRi acting upstream of the DDR cascade on multiple repair pathways and active regardless of genetic mutations without inducing resistance in tumor cells
AsiDNAtrade mimics DNA breaks in the tumor cell sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response
This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair machinery
1
1 Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193
2
3
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
9Wide therapeutic potential including different combinations and indications
November 2019
as a monotherapy
bull Selection of the best responding patients with stratification biomarkers
Up to 11 Million patients(incident population in 8MM)
with PARP inhibitors
bull Indications ovarian (ODD) breast HER2hellip
bull Expend PARPi use in both BRCAm amp BRCAwt
bull Abrogate resistance to PARPi
asymp 550000 patients1
(incident population in 8MM)
with radiotherapy
bull Indications sarcoma glioblastoma HampN lung cervix rectal cancers pediatric medulloblastoma
bull Radiosensitize and Synergy of efficacy
asymp 38 Million patients3
(incident population in 8MM)
HR Homologous recombination - OC Ovarian cancer - (TN)BC (Triple negative) Breast cancer - (N)SCLC (Non) Small cell lung cancer - HNC Head amp neck cancer - ODD Orphan Drug Designation - 1 OC + HER2 Neg BC (both BRCA wild-type) 2 OC + (N)SCLC + TNBC + HNC 3 All cancers (55 of incidence) Companyrsquos estimates in 8Major Markets (8MM) after GlobalData reports and Globocan 2018 data
with DNA-damaging chemotherapies
bull Indications OC (ODD) SCLC (ODD) NSCLC HNC (ODD) TNBC hellip
bull Synergy of efficacy with DNA breakers
asymp 13 Million patients2
(incident population in 8MM)
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
AsiDNAtrade
Robust preclinical amp translational data set supporting
clinical development
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
11AsiDNAtrade leads to cancer cell death and does not induce resistance
Treatment with AsiDNAtrade reduces cancer cells survival (1-30microM IC50)
In contrast to targeted therapies (eg PARPi) repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance
MDAMB231 ndash TNBC HR proficient(PARPi are ineffective on this cell line)
AsiDNA
BC227 ndash TNBC HR BRCA1 mutated
BC227
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
AsiDNA Talazoparib Olaparib
Surv
ival (
NT)
Source Onxeo data on fileNovember 2019
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
12AsiDNAtrade plus PARPi generates synergies in both HR deficient and proficient cancer cells and prevents resistance to PARPi
Expansion of PARPirsquos use to HR-proficient tumors combo shows the same efficacy in both HR deficient and proficient cancer cells
Synergistic efficacy combo leads to a rapid and complete inhibition of cancer cell survival not observed with PARPi alone
Prevention of the occurrence of PARPi-acquired resistance at low doses in several cancer cell lines
TNBCHR deficient(BC227)
SCLC(NCI-H446)
Olaparib 5 microM - Talazoparib 100nM - AsiDNAtrade 1microM Talazoparib 100nM ndash AsiDNAtrade 1microM
Source Onxeo data on fileNovember 2019
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
120
140
Olaparib Talazoparib
AsiDNA+Olaparib AsiDNA+Talazoparib
Surv
ival (
N
T)
1st cycle 2nd cycle 3rd cycle 4th cycle0
20
40
60
80
100
Talazoparib AsiDNA+Talazoparib
Surv
ival (
N
T)
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
13Combination of AsiDNAtrade with PARPi demonstrates synergy in HR proficient TNBC
AsiDNAtrade in combination with PARPi shows high efficacy in vivo in cancer cells non-sensitive to PARPi
Opportunity to expand PARPi indications to HR proficient tumors
NT olaparib AsiDNAtrade AsiDNAtrade + olaparib
Complete Response = 06 Complete Response = 28 Complete Response = 48 Complete Response = 57 0 25 50 71
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Source Onxeo data on fileNovember 2019
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
14Class-effect of the combination of AsiDNAtrade with PARPirsquos supportedby extensive preclinical testing
Both synergy and abrogation of resistance to treatment occur with all tested PARPi and regardless of the tumor type opening new opportunities for clinical applications
November 2019
Tumor model (cell lines primary tumors)
Treatment in combination Observed effect Reference
TNBC (MDA-MB-231xenograft mice model)
AsiDNAtrade + olaparib Complete response more than doubled Data on file
Resistant PDX ovarian model AsiDNAtrade + olaparib Synergy delaying tumor growth Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + olaparib or + talazoparib Resistance is prevented by co-treatment Data on file
Ovarian cancer AsiDNAtrade + niraparib Resistance is prevented by co-treatment Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Resistance is prevented by co-treatment Data on file
TNBC HR deficient (BC 227) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
SCLC (NCI-H446) AsiDNAtrade + talazoparib Rapid and complete inhibition of cancer cell survival Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + talazoparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + niraparib Synergistic antitumor effect Data on file
TNBC HR proficient (MDAMB231) AsiDNAtrade + olaparib Synergistic antitumor effect Data on file
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
15Combination of AsiDNAtrade with carboplatin shows synergy in resistant TNBC
0
100
200
300
400
500
600
700
800
900
1000
0 10 20 30 40 50 60 70 80 90 100
Mean
volu
mes (m
m3)
Time after treatment (days)
MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice
Group I vehicle (Nacl 09)
Group II AsiDNA (IP)
Group III carboplatin (IP)
Group IV AsiDNA (IP) + carboplatin (IP)
Endpoint1500 mm3
d - XX graft
Week 7Week 4Week 1
Treatment Median survival(days)
Vehicle NaCl 09 15x IP (n 6) 77
Carboplatin 3x 50 mgkg IP (n 8) 88
AsiDNA 15x 5 mg IP (n 8) 128
AsiDNA 15x 5mg IP + carboplatin 3x 50mgkg IP (n 10)
175
Source Onxeo data on fileNovember 2019
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
16Data support increased efficacy of the combination of AsiDNAtrade with DNA-damaging agents in multiple in vivo models
Tumor model (cell lines primary tumors)
Treatment in combination Route of administration Reference
Breast cancer (BC227 BC173 MDA-MB468 MDA-MB231) AsiDNAtrade standalone
Intratumoral + Peritumoral Subcutaneous Intraperitoneal (MDA-MB231) Data on file
Breast cancer (MDAMB231 BC227) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Glioblastoma AsiDNAtrade + Radiotherapy Intratumoral Coquery et al 2012
Cutaneous melanoma AsiDNAtrade + RadiotherapySubcutaneous PeritumoralIntratumoral + subcutaneous Peritumoral
Schlegel et al 2012Biau et al 2014
Colorectal cancer AsiDNAtrade + RFA (hyperthermia) Intratumoral + subcutaneous Devun et al 2014
Colorectal Liver metastasis (HT29) AsiDNAtrade + 5FU + oxaliplatin Intraperitoneal Herath et al 2016
HCC (HepG2) AsiDNAtrade + doxorubicin Intraperitoneal Herath et al 2016
Head amp neck (Hep2) AsiDNAtrade + Radiotherapy Intratumoral Quanz et al 2009
Head amp Neck (Hep2) AsiDNAtrade + carboplatin Intraperitoneal Data on file
Lung cancer (TC-1) AsiDNAtrade + carboplatin or cisplatin Intraperitoneal Data on file
HCC (VX2 rabbit) AsiDNAtrade + TACE (Doxorubicin) Transarterial Herath et al 2016
November 2019
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
AsiDNAtrade
Clinical data and perspectives
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
18Successful DRIIM study in metastatic melanoma
Proof of concept established in completed DRIIM Phase I trial1 Intratumoral administration + radiotherapy in metastatic melanoma
Overall response rate = 593
Complete response = 303 (CR from low-dose radiotherapy alone less than 102)
Partial response = 293
Durable response (up to 12-month follow-up period)
Before treatment 90 days after treatment
1 Le Tourneau et al Br J Cancer 2016 May 24114(11)1199-205 2 Olivier et al Cancer 2007 Konefal et al Radiology 1987 3 of lesions
IT administration of AsiDNAtrade confirmed safety signal of efficacy systemic passage suggested
November 2019
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
19
PHASE I
Open-label 3+3 dose escalation 22 patients
2 European countries FR BE
5 centers Paris(2)Toulouse Lyon Brussels
Study coordinator Pr C Le Tourneau (Institut Curie)
DSMB
OBJECTIVES To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD)
To evaluate the pharmacokineticspharmacodynamics (PKPD) effects of AsiDNAtrade based on biomarkers of activity in blood and in tumor tissues
APRIL 2018FIRST PATIENT DOSED
TREATMENT SCHEDULE
Dose Level 1
200 mg
Dose Level 6
1800 mg
3 patients
Dose Level 2
400 mg
4 patients
Dose Level 3
600 mg
3 patients
MAY 2019 END OF STUDY
1-hour IV infusion
DAY 1 21 2 3 8 15
CYCLE 1CYCLE 2 and beyond once a week
DRIIV-1 study evaluating AsiDNAtrade via IV administration all safety and activity endpoints metDNA Repair Inhibitor administered IntraVenously in patients with advanced solid tumors having failed previous anticancer therapies
Dose Level 4
900 mg
6 patients1 DLT
ACTIVE DOSES - THERAPEUTIC WINDOW
NOVEMBER 2018 BIOACTIVITY
Activity as early as dose level 2 MTD not reached at dose level 5
November 2019
Dose Level 5
1300 mg
6 patients1 DLT
SELECTED AS OPTIMAL DOSE FOR DRIIV-1b IN COMBO w CHEMO
Not administered sufficient therapeutic window
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
20DRIIV-1 study Safety Overview - DL1 to DL5n = 22 patients ndash 153 infusions
November 2019
AsiDNATM 200mg (DL1) 400mg (DL2) 600mg (DL3)
No drug-related serious adverse events
No dose-limiting toxicity
No cumulative relevant safety
Only grade 1 amp 2 drug-related adverse events
AsiDNATM 900mg (DL4) 2 related SAEs
Orthostatic hypotension grade 3 (unlikely related)
Hepatic enzyme increased grade 4 (possibly related) =gt 3 additional patients (DLT)
AsiDNATM 1300mg (DL5) 1 related SAEs
Hepatic enzyme increased grade 3 (unlikely related) =gt 3 additional patients (DLT)
Maximum tolerated dose (MTD) was not reachedFavorable safety profile at active doses providing a comfortable therapeutic window
Source Onxeo data on file
181 (89)
22 (11)1
204 adverse events
Grade 12 Grade 3 Grade 4
related 5
related 23
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
21DRIIV-1 study ndash Activity (PD) - Proof-of-Mechanism in man
Significant increase of activity biomarkers as early as DL2 (400 mg)Activity biomarkers increase gH2AX and pHSP90
Tumor proliferation biomarker decrease Ki67
Consistent activity in all patients tested from DL2 (400mg) to DL4 (900mg) supporting AsiDNAtrade target engagement via IV route
At DL3 (600mg) 2 patients w relapsed multi-treated mCRC controlled without
progression at the end of 2nd treatment cycle amp treatment maintained for 3 months
AsiDNAtrade robust target engagement via IV route is confirmed
DL3 (600 mg) selected as optimal dose for further combination studiesActivity
November 2019 Metastatic colorectal cancer - 21- day treatment cyclesSource Onxeo data on file
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
22DRIIV-1b study in combination with carboplatin with or without paclitaxelin patients with advanced metastatic solid tumors (eligible to the selected chemotherapy regimen)
November 2019
Positive intermediate results from Part 1 of the studyPart 2 started with first results expected by year end 2019
PHASE 1b
Extension of DRIIV-1 mono study
Open-label 3+3 patient cohort
Up to 15 patients
2 centers in Belgium
DSMB
OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination
To detect signal of efficacy (RECIST criteria)
To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)
TREATMENT SCHEDULEASIDNATM 1-hour IV infusion
AsiDNAtrade
DAY 1 22 2 3 8 15
CYCLE 1
Q3 2019PART 1 INTERMEDIATE RESULTS
29
Carbo 3 w CarboPacli w PacliPacli Pacli
AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade
END Q4 2019PRELIMINARY EFFICACY OUTCOMES
AsiDNAtrade 600 mg
Part 1 carboplatin
AsiDNAtrade 600 mg
carboplatin + paclitaxel
AsiDNAtrade 400 mg
carboplatin + paclitaxel
Part 2(ongoing)
+
+
+
6 pts
6 ptsPart 3
3 patients whose metastatic tumors were progressing at inclusionStable disease (no tumor progression) in 23 pts still being treatedSatisfactory tolerance of the combination
3 pts
CYCLE 2 and beyond once a week
If necessary (DLT)
MAY 2019FIRST PATIENT DOSED
H1 2020 END OF STUDY
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
23AsiDNAtrade IV Current Clinical Program Solid tumors with high unmet medical needs
November 2019
Synergy
Phase 1b StudyEfficacySafety of the combo AsiDNAtrade with carboplatin +
paclitaxel
bull Advanced metastatic solid tumors eligible to carboplatin with or without paclitaxel (TNBC Ovarian cancers Lung Head amp Neckhellip)
bull Objectives confirm AsiDNAtrade readiness for phase 2 in combo (safety profile and efficacy signal detection)
FPI May 2019 ndash positive results from part 1 with carboplatinFirst results from part 2 (carboplatin + paclitaxel) expected late Q4 2019Next step Phase IIa to start in 2020
Resistance
Phase 1b2 StudyAbrogation of PARPi
resistanceAsiDNAtrade in combo with PARP inhibitor
bull Ovarian Breast cancer bull Objectives confirm AsiDNAtrade potential to abrogate tumor resistance to PARPi andor
synergistic effects
FPI expected H1 2020
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
FINANCIALS amp OUTLOOK
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
25
Financiegravere de la Montagne16
Other institutions19
Retail60
Misc 5
Financials and share structure
Cash position of euro63m at 06302019
New equity line set up in November 2019 provides cash runway to Q3 2020
Shares outstandingFully diluted
57m596m
Dual listing Euronext Paris amp Nasdaq Copenhagen
ISIN FR0010095596
at 083119 at 013119
November 2019
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
26
AsiDNAtrade OX401
Today
On-going preclinical work on new combinations
Preliminary Results of DRIIV 1b
Filing of Phase 1b2 combo study w PARPi
New compound from platONtrade entersregulatory preclinical evaluation and CMC In-vitro validation
H1 2020
H2 2020
DRIIV 1b full data set
Niraparib combo study ( ovarian cancer) preliminary data In-vivo proof-of-concept
Niraparib combo study additional data
Multiple near to mid-term value-creating RampD milestones
November 2019
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
APPENDICES
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
28AsiDNAtrade Publications (12)
Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298
Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)
Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706
Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15
Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75
Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33
Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567
Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18
Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37
Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55
DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313
Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46
A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44
An update on PARP inhibitors for the treatment of cancer Benefif S et al
Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235
The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22
Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860
Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205
Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444
Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
29AsiDNAtrade Publications (22)
Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216
The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27
Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549
Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3
AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871
Posters AACR 2013
Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment
ASCO 2015
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma
AACR 2017
AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
AACR 2018
AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo
AACR 2019
Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastoma subtypesAsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom
CONTACTSJudith Greciet ndash CEO
Nicolas Fellmann ndash CFOTel +33 1 45 58 76 00 contactonxeocom
COMPANY INFORMATIONwwwonxeocom