INC.

Leerink Global Healthcare Conference

Wolfgang Oster, MD, PhD, Chief Executive OfficerLee Schalop, MD, Chief Business Officer

February 12, 2015

2

• Novel class of compounds with orthogonal profile• Compelling efficacy in aggressive and refractory liquid and solid

tumors • Agnostic to resistance to targeted therapy and chemotherapy• No dose-limiting toxicities at therapeutic or exaggerated doses in

preclinical studies• Phase I/II trials activated in hematological malignancies and solid

tumors• Landmark Alliance with MD Anderson for early clinical

development in hematological malignancies • Solid tumor trials spearheaded by leading cancer centers under

co-funding/non-dilutive structures (CINJ, MGH, FCCC)

www.oncoceutics.com

Synopsis

3

• Phenotypic screen selected to discover novel therapeutic mechanisms, unlike target screening

• Goal of screen was to identify a small molecule that engages natural pathways that kill treatment-resistant tumor cells and leave normal cells unharmed

www.oncoceutics.com

Discovery of Novel Class

0E+00 1E+04 2E+04 3E+04 4E+04 5E+040

0.5

1

1.5

2

Reporter Signal

TRA

IL R

epor

ter

Indu

ctio

n

Can

cer C

ells

Nor

mal

Cel

ls

Dividing CellsDeadCells

Cell Cycle Analysis

Sub-G1

4

• Uses a differentiated mechanism to manipulate a collection of signaling pathways that cancer cells rely on and that the immune system has evolved to eradicate them

www.oncoceutics.com

Engaging Critical Cancer Pathways

• Some of the most successful oncology pathways are engaged:• Growth factor/ Ras signaling• ER stress• Immunosurveillance

5www.oncoceutics.com

• Novel pharmacophore, distinct from approved/investigational drugs > NCI library > Pubchem

• Proprietary salt • Highly stable and soluble• Orally active • Penetrates BBB• Unique PK/PD enables infrequent dosing

Chemical Characteristics

ONC201 Temozolomide Vorinostat Bortezomib Ibrutinib0

250

500

750

1000

1250

1500

# R

elat

ed C

ompo

unds

Structure Similarity Search of >63 Million Known Compounds

ONC201Angular Structure

6

• Chemical and biological studies have revealed a structure-activity relationship (SAR)

• The unique therapeutic potential of ONC201 is extended to a specific subset of analogs

• A host of properties can be manipulated to open additional therapeutic opportunities:

• Potency • Activity spectrum• PK • Metabolism • Biodistribution

www.oncoceutics.com

Analog Program

7www.oncoceutics.com

Compound Use Phase StatusONC201 po Solid Tumors Phase I Enrolling

ONC201 po Liquid Tumors Phase I/II Initiating

ONC201 po + chemo Solid & Liquid Tumors Phase Ib Protocol development

ONC201 iv Alternative to po Pre-IND Active

ONC201 (alternative formulation) Alternative clinical utility Pre-clinical Active

ONC201 analog 1 Various Tumor Types Pre-clinical Active

ONC201 analog 2 Various Tumor Types Pre-clinical Active

Portfolio• Oncoceutics has several products in different stages

of preclinical to clinical development • Clinical applications of ONC201 include diverse

tumor types and other products provide alternative drug profiles and potential applications

8www.oncoceutics.com

Discovery of Unexpected Activity• ONC201 was previously deemed inactive by NCI in

vitro, providing intellectual property opportunities• This observation increased the need for external

validation

9

Patent Issued• Method of Use in Brain Cancer

Patents Pending • Method of Use in Other Cancers • Novel Salts • Dosing• Schedule• Formulations• Combination with Other Drugs• Methods of Administration• Analogs (COM)

www.oncoceutics.com

Intellectual Property

10

Keith Flaherty, MD – Clinical developmentHensin Tsao, MD, PhD – Mutant BRAF melanomaAndrew Chi, MD and Tracy Batchelor, MD, PhD – GBM

Michael Andreeff, MD, PhD and Hagop Kantarjian, MD – Leukemia, SPORE Michael Wang, MD & Larry Kwak, MD – NHLMadeleine Duvic, MD – Sezary syndrome Andreas Hayes Jordan, MD - DSRCTAnthony Conley, MD – Sarcomas

Joseph Bertino, MD – Prostate CancerBruce Haffty, MD – Radiation, SCC

Fahd Al-Mulla, MB, ChB, PhD, FRCP – Breast cancer , KFAS Foundation funded

Haiching Ma, PhD – Target identification

Cyril Benes, PhD (Harvard) –1,000 cancer cell line panel

External Validation

Martine Piccart, MD – Breast Cancer Kensuke Kojima, MD, PhD – Proteomics

Wafik El-Deiry, MD, PhD, FACP – Combinations, MOAAnthony Olsznaski, MD – Phase I dose intensification

www.oncoceutics.com

11

• Efficacy: Preclinical profile has been validated by multiple leading investigators in state-of-the-art refractory models: • Cell lines (>500)• Primary patient samples (>25)• In vivo models (xenografts, orthotopic, transgenic)

• Safety: No effects on normal cells or normal tissues in GLP toxicology at >10 therapeutic dose

Reproducible Efficacy and Safety Profile

www.oncoceutics.com

NOAEL >10-fold

therapeuticdose

Species dose(mg / kg)

Human equivalentdose (mg)*

Ratio to Expected

Therapeutic Dose

Cohort 1 0 0 N/ACohort 2 12.5 125 1Cohort 3 125 1250 10Cohort 4 225 2250 18Cohort 1 0 0Cohort 2 4.2 125 1Cohort 3 42 1250 10Cohort 4 120 3571 28.6

* Allometrically scalled to a human fixed dose

Rats

Dogs

12

• Effective in tumor cells with complex resistance to powerful approved anti-cancer therapies:

• Interim analysis of MGH/Sanger/Wellcome Trust 1000 cell line panel screen confirmed mutation-agnostic efficacy across 428 genes curated for cancer relevance

Efficacy in Therapy-Resistant Cancers

www.oncoceutics.com

• 5-FU (Efudex)• Doxorubicin (Adriamycin) • Temozolomide (Temodar)• Cetuximab (Erbitux)• Gefitinib (Iressa)• Erlotinib (Tarceva)

• Trastuzumab (Herceptin) • Lapatinib (Tykerb)• Vemurafenib (Zelboraf)• Ibrutinib (Imbruvica)• Bortezomib (Velcade)

13

Spec

ific

Apop

tosis

• ONC201 is active in blastic (mt p53) MCL patient samples

• Robust ONC201 activity is observed in ibrutinib-refractory MCL

Ishizawa and Andreeff et al.

ONC201 Kills Highly Resistant Lymphomas

Apo

ptos

is:

www.oncoceutics.com

14

• Single dose oral ONC201 doubled the survival of mice with intracranial brain tumors

• In combination with Avastin, ONC201 tripled the survival of mice with intracranial brain tumors and was well tolerated

0 10 20 30 40 50 60 70 80 90 1000%

50%

100%Control TIC10 bev TIC10 + bev

Days

Sur

viva

l Befo

re R

x1

week

Vehicle ONC201ONC201 + bevONC201 bevVehicle

ONC201 Kills Brain Tumors

www.oncoceutics.com

Allen and El-Deiry et al

15

New GBM IC50GBM8: 300 nMGBM18: 4-5 uM

Recurrent GBM IC50GBM67R: 4 uM

GBM152: 700-800 nM

• ONC201 kills primary GBM cells in 3D culture (neurospheres) enriched for cancer stem cells

• Effective in both newly-diagnosed and recurrent GBM samples

ONC201 Kills Brain Tumors

Andrew Chi and Tracy Batchelor

www.oncoceutics.com

16

Spec

ific

Apop

tosis

ONC201 Kills Tumor But Not Normal Cells

• ONC201 does not induce apoptosis in normal bone marrow at highly efficacious doses

www.oncoceutics.comIshizawa and Andreeff et al.

17www.oncoceutics.com

Spec

ific

Apop

tosis

• Depletion of cancer stem cell efficacy has been documented in several aggressive cancers in vitro : AML, GBM, CRC

ONC201 Kills Cancer Stem Cells

Ishizawa and Andreeff et al.

• ONC201-induced anti-cancer stem cell effects have also been demonstrated in several CRC models in vivo

18

NHL, MM, leukemias, and GBM selected based on:

• Robust induction of apoptosis• Consistent efficacy in primary patient samples• Sensitivity pattern

• GI50/potency• Confirmed by MGH/Sanger/Wellcome Trust screen

• Engages relevant mechanisms for these tumors• Medical need indications with expedited approval

options • Indications with attractive addressable market

opportunity• Broad and diverse clinical program: multiple shots on

goal

www.oncoceutics.com

Tumor Type Selection Criteria for Clinical Trials

19

Active Clinical Trials• Cancer Institute of New Jersey: Phase I Solid Tumors• MD Anderson Cancer Center: Phase I/II Leukemia

Clinical Trials in Initiation• MD Anderson Cancer Center: Phase I/II Lymphoma

Planned Clinical Trials

• MGH / Dana Farber: Phase II GBM

Additional Opportunities

www.oncoceutics.com

Clinical Trials

20

• Oncoceutics and collaborative groups have been awarded the following highly competitive grants for research and development

• Represents significant endorsement of the novelty, therapeutic potential, and commercial viability of the company’s technology by NCI and others

Competitive Grant Awards

Title Amount Institution/ Mechanism

Development and Commercialization of Novel Cancer Therapeutic TIC10  

$1.3mm PA DOH Commercializatio

n Grant

Target Identification of ONC201, a First-in-Class Drug to Treat Glioblastoma

$25,000 Musella Foundation

Clinical Efficacy of the Antitumor Agent ONC201 in GBM

$1.15mm  

NIH SBIR (Impact Score 20; pending

official notice)

TRAIL Upregulation by TIC10 Analogs

$225,000  

NIH SBIR

TIC10 anti-tumor effect through regulation of Foxo3a and TRAIL

$1.9mm NIH RO1

www.oncoceutics.com

21

• Significant validation through partnerships with leading cancer centers

• Creating awareness and interest with key opinion leaders

• Non-dilutive funding >$10mm

ONC201 Academic-Corporate Partnerships

www.oncoceutics.com

22

• Funding in place to complete phase I/II programs with >150 patients at >4 clinical sites

• Expected to arrive at clinical results to devise NDA-directed strategy

• Interested in development/commercial partnerships for lead compound ONC201 and analogs

www.oncoceutics.com

Looking Forward Through 2016