INC.

Leerink Global Healthcare Conference

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

February 12, 2015

• 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

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• 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

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0

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1

1.5

2

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

TR

AIL

Rep

ort

er I

nd

uct

ion

Reporter Signal

Can

cer C

ells

N

orm

al C

ells

Dividing Cells Dead Cells

Cell Cycle Analysis

Sub-G1

• 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

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JAK/STAT�

• Some of the most successful oncology pathways are engaged:

• Growth factor/ Ras signaling

• ER stress

• Immunosurveillance

www.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

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ONC201 Temozolomide Vorinostat Bortezomib Ibrutinib

# R

elat

ed C

ompo

unds

Structure Similarity Search of >63 Million Known Compounds

ONC201 Angular Structure

• 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

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www.oncoceutics.com

Compound Use Phase Status ONC201 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

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www.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

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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

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Keith Flaherty, MD – Clinical development Hensin Tsao, MD, PhD – Mutant BRAF melanoma Andrew Chi, MD and Tracy Batchelor, MD, PhD – GBM

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

Joseph Bertino, MD – Prostate Cancer Bruce 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, MOA Anthony Olsznaski, MD – Phase I dose intensification

10 www.oncoceutics.com

• 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 11

NOAEL >10-fold

therapeutic dose

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

• 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 12

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

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

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 13

• 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%

50%

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0 50 100

Surv

ival

Days

Control TIC10 bev TIC10 + bev

Befo

re R

x 1

wee

k

Vehicle ONC201 ONC201 + bev ONC201 bev Vehicle

ONC201 Kills Brain Tumors

www.oncoceutics.com

Allen and El-Deiry et al

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New GBM IC50 GBM8: 300 nM GBM18: 4-5 uM

Recurrent GBM IC50

GBM67R: 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 15

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.com Ishizawa and Andreeff et al.

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www.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. 17

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

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

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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

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• 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 Commercialization

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 20

• Significant validation through partnerships with leading cancer centers

• Creating awareness and interest with key opinion leaders • Non-dilutive funding >$10mm

ONC201 Academic-Corporate Partnerships

21 www.oncoceutics.com

• 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

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