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CORPORATE PRESENTATIONJUNE 2019
Subject to closing of CytoSen acquisition
Euronext: KDS
Patient-specific cell therapy in hemato-oncology to improve outcomes of hematopoietic stem cell transplantation
Leveraging the natural strengths of humanity and our collective immune systems to source the
best cells for life
Disclaimer
These slides and the accompanying oral presentation contain forward-looking statements and information. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels or activity, performance or achievements to be materially different from those anticipated by such statements. The use of words such as “may”, “might”, “will”, “should”, “could”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “project”, “intend”, “future”, “potential” or “continue”, and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding (i) the initiation, timing, cost, progress and results of our preclinical and clinical studies and our research and development programs, (ii) our ability to advance product candidates into, and successfully complete, clinical studies, (iii) the timing or likelihood of regulatory filings and approvals, (iv) our ability to develop, manufacture and commercialize our product candidates and to improve the manufacturing process, (v) the rate and degree of market acceptance of our product candidates, (vi) the size and growth potential of the markets for our product candidates and our ability to serve those markets, and (vii) our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates, are forward looking. All forward-looking statements are based on current estimates, assumptions and expectations by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. This presentation is not, and nothing in it should be construed as, an offer, invitation or recommendation in respect of our securities, or an offer, invitation or recommendation to sell, or a solicitation of an offer to buy, any of our securities in any jurisdiction. Neither this presentation nor anything in it shall form the basis of any contract or commitment. This presentation is not intended to be relied upon as advice to investors or potential investors and does not take into account the investment objectives, financial situation or needs of any investor.
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Kiadis: Combining T-cell and NK-cell platforms to fight cancer
Patient specific cell therapy in hemato-oncology,
combining innate and adaptive immune system
Strong US presence, e.g., BMT-CTN and SAB
Key medical and finance functions in US
ATIR101 US FDA RMAT and US/EU Orphan drug designations
ATIR101: phase 3 enrolling; MAA on file in EU
CSTD002: clinical trials to start in 2020
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HSCT: hematopoietic stem cell transplantation; Haplo: haploidentical (genetically half matched); allodepleted T-cells: T-cells without patient specific T-cells that could cause GVHD; GVHD: Graft versus Host disease; RMAT: Regenerative Medicine Advanced Therapy (‘breakthrough designation’); PTCy: post transplant cyclophosphamide
Develop cancer NK-cell therapies (e.g., treat
AML R/R)
Potential to Revolutionize haplo HSCT with
combination of T-cell and NK-cell therapies
Two platforms: ATIR101: allodepleted T-cells
CSTD002: potent NK cells
Kiadis to acquire CytoSen in all stock transaction
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Consideration • 1.94 million shares of Kiadis stock to be paid to CytoSen shareholders
Potential milestones • Up to an additional 5.82 million shares of Kiadis stock based on successful achievement of six clinical development and regulatory milestones, through first FDA approval
Lock-up • The majority of Kiadis shares issued to the CytoSen shareholders at closing, including to its Executive Chairman, CEO and founders, will be subject to a lock-up for a period of two years
Closing • Shareholder approvals received, expected to closing in the coming days
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Leveraging natural strengths of human immune system
“… the fields of NK-cells and T-cells are enormously synergistic and the combination could potentially
help patients with devastating diseases.”
“NK-cell therapy could significantly advance the field of immuno-oncology.”
Dr. Carl JuneCAR-T pioneer & future member of Kiadis’ SAB
The human immune system uses both the innate and adaptive arms
5Illustration Source: Smyth, NATURE Reviews: Cancer; November 2002, Volume 2.
Kiadis pipeline
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Orphan Drug & RMAT Designations
Orphan Drug Designation
Indication Development Phase 3 Filing CatalystsCommercial
Rights Status
ATIR101 ‘Safe’ T-cells
Adjunct to HSCT (EU)
• EU Approval (2019)• EU Launch (first
patient, late 2019)
• Responding to EMA Day 180 questions end May 2019
Adjunct to HSCT (US)
• Phase 3 enrollment and interim read out (2021)
• RMAT ‘breakthrough’ designation
CSTD002Potent
NK-cells
Adjunct to HSCT
• Start trial with BMT-CTN (2020)
• Proof-of-concept at MDACC (25 patients)
Cancer treatment
• Start AML R/R trial (2020)
• Proof-of-concept at MDACC for AML R/R (8 patients)
Kiadis’ first programs: help people with blood cancer
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people living with LEUKEMIAS
Globally
~400,000
Sources: Deschler B et al. Acute Myeloid Leukemia: Epidemiology and Etiology. Cancer. 2006. 2009-2107; World Health Organization. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. Available at: http://www.who.int/selection_medicines/committees/expert/20/applications/AML_APL.pdf.; Passweg, NATURE 06Feb19 (nature.com/articles/s41409-019-0465-9); D’Souza A, Fretham C.: CIBMTR summary slides, 2017. Available at: http://www.cibmtr.org
are diagnosed with ACUTE LEUKEMIAS
– acute myeloid leukemia (AML),
acute lymphoblastic leukemia (ALL) and
myelodysplastic syndrome (MDS)
– which are AGGRESSIVE
and OFTEN FATAL
~55%OF PATIENTS
Leukemia is CANCER of
IMMUNE system CELLS that
compromises immune function
HSCTs(US and EU)
AUTOLOGOUS (~55%) (utilizing patient
stem cells)OR
ALLOGENEIC (~45%)(utilizing donor
stem cells)
~65,000 Allogeneic HSCT often the onlyPOTENTIALLY
CURATIVE APPROACH available;
kills the diseased immune system
of the patient and REPLACES WITH
THE HEALTHY IMMUNE SYSTEM
of the donor
Allogeneic HSCTs: Outcomes need to improve
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GVHD • T-cells from donor recognizing patient tissue as foreign and attacking patient, due to genetic differences
Implications of GVHD
• Skin, eye, mouth or GI tract disease; immunodeficiency, muscle constriction, bone loss, pulmonary disease, thyroid disfunction, solid tumors, sleep deprivation, depression
Treatment • Immunosuppression
Impact of severe GVHD
• 2-4x higher rate of death / lower overall survival• Quality of life worse than vision impairment, MS• Side effects immunosuppression (diabetes, renal failure)• 75% of patients lose 3 years earnings, 25% permanently
The ‘ideal’ transplant: give T-cells and NK-cells that protect; avoid T-cells that attack; avoid immunosuppressants.
OF ALLO HSCT PATIENTS*
ONLY
have long term survival without severe GVHD or
relapse
GRAFT HOSTvs
Mortality/morbidity Relapse GVHD
CHALLENGES
Infections
Sources: McCurdy SR, et al. Haematologica 2017; 102:391–400; Solh M, et al. Biol Blood Marrow Transplant 2016.; Pidala et al 2011, Pasquini 2018, Khoury 2017, Solh 2018; Jones 2016; Koreth 2013;
~30%
Allogeneic HSCT: Haplo-identical transplants growing
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MATCHED (UN)RELATED DONOR (MRD / MUD)
HAPLOIDENTICAL WITH PTCy (Post Transplant Cyclophosphamide)
Patients relapse during donor search; Only half of patients get transplanted
Relapse after transplant; Immunosuppression and toxicity
Availability varies with ethnicity Almost always available (half matched, e.g., parent or child)
~27,000 PER YEAR ~4,200 PER YEAR
Sources: Passweg, NATURE 06Feb19 (nature.com/articles/s41409-019-0465-9); D’Souza A, Fretham C.: CIBMTR summary slides, 2017. Available at: http://www.cibmtr.org*Weighted average of 5 PTCy/MUD comparison publications in review Fuchs E 2017 (n=463 PTCy and n=2647 MUD)
38%
53%
38%
51%
26% 27%
45%49%
Acute GVHD II-IV
Chronic GVHD
Relapse Survival
Haplo with PTCyMatched Unrelated Donor
Haplo PTCy versus Matched Unrelated Donor(up to 3 yr follow up)*
Suppress GVHD causing T-cells (but also protective NK/T-cells) with
cyclophosphamide and immunosuppression
Does not reflect additional survival benefit of haplo due to (faster) availability of donor
ATIR101 T-cell therapy program
After T-cell depleted Haplo HSCT
ATIR101: allodepleted T-cells after T-Cell depleted haplo HSCT
Apheresis of patient and donor and
centralproduction
Conditioning of patient, apheresis of donor, graft manipulation,
graft infusionATIR101
Produce ATIR101 5 days
(14 days to interim release)
Infuse ATIR101 30 days after graft infusion
T-cell depleted Haplo HSCT
T-cells removed from graft
Conditioning of patient, apheresis of donor,
graft infusion
Haplo HSCTUnmanipulated graft,
with T-cells
Cyclophos-phamide and
immuno-suppression
Cyclo-phosphamide3-5 days after graft infusion
No immuno-suppression (no T-cells in
graft)
ATIR101 ‘Safe’ T-cells
Haplo HSCT with PTCy
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ATIR101: allo-depleted T-cell therapy, alloreactive T-cells removed ex vivo
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Mix donor immune cells with patient material; alloreactive (GVHD
causing) T-cells become activated
Add light sensitive compound that gets trapped in activated
(GVHD causing) T-cells
Then kill activated (GVHD causing) T-cells with green light; ATIR101 contains
remaining allo-depleted T-cells
ATIR101: kill cells that attack ex vivo; infuse cells that protect; avoid immunosuppressants
ATIR (n=37) Historical controls; n=64)
ATIR101: Phase 2 versus T-cell depleted haplo HSCT
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58%[44-77*]
All data at 1 year; Matched patients; ATIR ITT: all patients undergoing HSCT; ATIR status 1 June 2018 (3 patients at risk) single dose; *95% confidence interval.
23%[14-37*]
Overall Survival
Severe chronic GVHD 0% 7%
Acute grade III/IV GVHD 5% 6%
ATIR101: Protective and safe T-
cells that:
Improve overall survival
(p=0.005)
T-cell depleted HSCTT-cell depleted HSCT plus ATIR101
Do not cause (increase in) severe GVHD
Basis for ATIR101 Phase 3 design: GRFS versus PTCy
14Sources: Sohl 2016; McCurdy 2017 (Johns Hopkins); Solh 2016 (Northside); ATIR ITT: all patients undergoing HSCT; ATIR status 1 June 2018 (3 patients at risk) single dose; *ASH Poster, Steven Devine, CIBMTR; *Disease Risk Index largest prognostic factor for OS/GRFS, normalization based on GRFS for each DRI category in papers
PTCy (Johns Hopkins, single
site, 372 patients*)40%
PTCy (Northside, single site,
128 patients*)30%
GRFS for ATIR and PTCy1 year; normalized for Disease Risk Index*
GRFS for MRD/MUD/PTCySurvival without Relapse, Grade III/IV GVHD, chronic
GVHD requiring systemic immunosuppression
ATIR101 (phase 2, 37
patients)53%
ATIR101: Phase 3 (CR-AIR-009), versus PTCy
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RRandomized / Controlled(1:1)80% power to detect 16% GRFS treatment effect
Haplo HSCT (TCD) plus ATIR: T-cell deplete CD34+HSCT plus ATIR 2 mln cells/kg at 30 days
Haplo HSCT with PTCy: T-cell replete HSCT with 50 mg/kg cyclophosphamide at days 3 and 5 post HSCT & prophylactic immunosuppressants
OBJECTIVE: Demonstrate superior clinical benefit and collect pharmacoeconomic data
PRIMARY ENDPOINT: GVHD-Free & Relapse-Free Survival (GRFS)- Primary analysis: at 156 events (11,4% GRFS
treatment effect)- Interim analysis: at 105 events (17,6% GRFS
treatment effect, hazard ratio 0.61)
SECONDARY ENDPOINTS: Overall Survival (OS), Progression Free Survival (PFS), Relapse, Non Relapse Mortality (NRM)
OTHER:Randomized at enrollment; Balanced conditioning regimens; Stratification for Disease Risk Index, disease and treatment site
AML / ALL / MDS
250
CENTERS
~50EU, US, Canada
and Israel
PATIENTS
ATIR101: EMA filing and EU Launch Preparation
• Building medical and commercial teams- Medical affairs- Marketing, market access,
commercial operations, account directors
• Developing reimbursement dossiers
• Establishing own Amsterdam manufacturing facility and patient specific supply chain
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EMA FILING AND LAUNCH PREPARATION
Belgium
Spain Italy
Germany
Sweden
LAUNCH COUNTRIES (ACCESS ON PHASE 2)
• Filed based on Phase 2 with historical control• Submitting answers to EMA day 180 2nd list of
questions end of May• Building medical and commercial teams
- Medical affairs- Marketing, market access, commercial operations,
account directors
• Developing reimbursement dossiers (countries with market access possible on Phase 2 data)
• Establishing own manufacturing (Amsterdam) and patient specific supply chain
CSTD002 NK-cell therapy program
After Haplo HSCT with PTCy
CSDT002: potent NK-cells after haplo HSCT with PTCy
Conditioning of patient, apheresis of donor,
graft infusion
Haplo HSCTUnmanipulated graft,
with T-cells
Cyclophos-phamide and
immuno-suppression
Cyclo-phosphamide3-5 days after graft infusion
Collection of donor blood and central production
Produce CSTD00214 days
CSTD002
Infuse CSTD002-2, +7 and +28days after graft
infusion
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CSTD002Potent NK cells
Conditioning of patient, apheresis of donor,
graft infusion
Haplo HSCTUnmanipulated graft,
with T-cells
Cyclophos-phamide and
immuno-suppression
Cyclo-phosphamide3-5 days after graft infusion
Haplo HSCT with PTCy
NK-cell program – strong scientific roots (CSTD002)
Dean Lee, M.D., Ph.D.Co-founder of CytoSenDirector of the Cellular Therapy and Cancer Immunotherapy Program for Nationwide Children’s Hospital’s Division of Hematology/Oncology/BMT andCenter for Childhood Cancer and Blood Diseases
Robert Igarashi, Ph.D.Co-founder and Chief Science Officer of CytoSen Former Assistant Professor in the Department of Chemistry at the University of Central Florida, with a joint appointment in the Burnett School of Biomedical Sciences
Stefan O. Ciurea, M.D.Co-founder of CytoSenAssociate Professor, Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
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Best-in-class potential for high dose potent NK-cell platform
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Dosing High doses (10x endogenous levels possible)
In vivo persistence Limited telomere shortening, zero senescence
Anti-tumor activity High cytotoxicity (ADCC, IFNγ and TNFα)
Breadth of response Effective response in over 10 cancer targets
Activation Upregulated activating receptors (e.g., NKG2D, CD16)
Cryopreservation Industry standard cryopreservatives and thawing
Manufacturing Scalable, wave bags, closed system
Regulatory Irradiated nanoparticle stimulation, not with tumor feeder cell line
mbIL21
4-1bbL
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Expansion and activation of natural haplo donor NK-cells with patented PM21 nanoparticles with mbIL21 and 41bbl
antigens
High dosing, cytotoxicity, persistence and activation
CSDT002: MDACC proof-of-concept* as adjunct to HSCT-PTCy
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Size Dose levels Timing Follow up Outcomes
n=25 104 to 108
cells/kgDay -2, +7, +28
from graft infusion28 months
(0.9-48)
• Improvement in relapse rate, PFS and OS• Reduction in reactivation of CMV/BKV• No severe acute and chronic GVHD
Improvement versus matched contemporaneous MDACC control and versus CIBMTR
control
*NK-cells produced with feeder cells expressing mbIL21 and 41bbl, not with nanoparticles; n=13 Phase 1 dose finding (published in Blood), n=12 Phase 2 at highest dose (presented at ASCO and Haplo2018); Ciurea SO, et. al. Blood 2017, (link to paper); Ciurea SO EMBT Mar2018; Ciurea SO, Haplo2018, Nov2018
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8%
45%
CSDT002: PoC* for treatment of AML (R/R, 2nd line salvage)
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Site Size Patients: AML R/R 2nd line salvage
Timing of dose Follow up Outcomes
MD Anderson n=8
• 4 median prior treatments• 3/8 prior HSCT• 43% median BM blasts
6 doses (11 days)
329 days(71-730)
• CR/CRi: 75% (day 30)• HSCT: 50%• Survival: 37,5% (1 year)
MD Anderson and Brazil
N=13• 4 median prior treatments• 7/13 prior HSCT • 45% median BM blasts
6 doses (11 days)
202 days (39-590) • CR/CRi: 69%
* NK-cells produced with feeder cells expressing mbIL21 and 41bbl, not with nanoparticles; Ciurea SO, et. al. ASCO June2018; Ciurea SO Haplo2018. Nov2018 22
Case example (AML, male, 25 yrs):• 8 lines of prior treatment, incl prior failed HSCT• Active disease, 90% BM blasts• Treated with NK cells plus FLAG, no subsequent HSCT• No treatment side effects• Complete response• Ongoing MRD decrease and immunologic activity (at 120 days)• Alive at 1 year; Relapsed/death at 2 years
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Multiple generations with potential to revolutionize haplo HSCT
Potentially suitable for even wider group of patients
Adjunctive dose
Haplo HSCT with PTCy T-Cell depleted with PTCy T-Cell depleted
Status Standard of care Phase 3 and EU registration
MDACC Proof of concept
Potential future standard of care
‘Safe’ T-cells +/- + +/- +Potent NK-cells - - + +No immunosuppression - + - +
Potential benefits:
GVHD & Relapse-free Survival; No immuno-suppression
Survival & relapse
Survival, relapse & GVHD;
No immuno-suppression
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ATIR101 ‘Safe T-cells’
CSTD002Potent NK-cells
ATIR101 andCSTD002
Standard of Care PTCy
Rapid growth since 2012
Strong leadership team
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ARTHUR LAHRChief Executive Officer
SCOTT A. HOLMESChief Financial Officer
DIRK de NAEYERChief Operations Officer
ANDREW SANDLER, MDChief Medical Officer
ROBERT FRIESENChief Scientific Officer
MARK WEGTER, ChairmanPartner LSP
BERNDT MODIGFormer CFO Prosensa
OTTO SCHWARZFormer COO, Actelion
ROBERT SOIFFER, MDProf Harvard, Director HSCT Dana Farber, Chair CIBMTR, board member NMDP
MARTIJN KLEIJWEGTFounder of LSP
SUBHANU SAXENAFormer head of global product strategy and commercialisation, ExCom member, Novartis
SELECT MANAGEMENT TEAM MEMBERS SUPERVISORY BOARD
JONATHAN SWEETINGSr. VP, Commercial EU
Kiadis news flow
2019
2020
2021
• Potential EU approval of ATIR101
• Launch ATIR101 in EU (late 2019, first patient)
• Continued enrollment in global Phase 3 for ATIR101
• Establish Scientific Advisory Board
• Continued enrollment in global Phase 3 for ATIR101
• Initiate clinical trial of CSTD002-NK in HSCT
• Initiate clinical trial of CSTD002-NK in AML R/R
• Continued launch of ATIR101 in EU
• Initiate additional trials with ATIR and/or CSTD002-NK
• Complete enrollment in Phase 3 for ATIR101
• Interim data for Phase 3 for ATIR101 (upon 105 events)
• Interim data for clinical trial(s) with CSTD002-NK
• Continued launch of ATIR101 in EU
• Initiate additional trials with ATIR and/or CSTD002-NK
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When it comes to life-threatening diseases, we are one family. Kiadis is re-imagining medicine by leveraging the natural strengths of humanity and our
collective immune systems to source the best cells for life. Our uncompromising approach to serve patients, their families and care givers aims to minimize harm and maximize help – delivering personalized treatments for every single
patient to offer hope, reduce suffering and provide new life.
PATIENT CARE TEAMFAMILY