1. INC.
Leerink Global Healthcare Conference
Wolfgang Oster, MD, PhD, Chief Executive Officer
Lee 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
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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
3
0
0.5
1
1.5
2
0.E+00 1.E+04 2.E+04 3.E+04 4.E+04 5.E+04
TRAILReporterInduction
Reporter Signal
CancerCellsNormalCells
Dividing CellsDead
Cells
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
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JAK/STAT
• Some of the most
successful oncology
pathways are engaged:
• Growth factor/
Ras signaling
• ER stress
• Immunosurveillance
5. 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
5
0
250
500
750
1000
1250
1500
ONC201 Temozolomide Vorinostat Bortezomib Ibrutinib
#RelatedCompounds
Structure Similarity Search of
>63 Million Known Compounds
ONC201
Angular 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
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7. 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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8. 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
8
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
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10. 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 CancerKensuke Kojima, MD, PhD – Proteomics
Wafik El-Deiry, MD, PhD, FACP – Combinations, MOA
Anthony Olsznaski, MD – Phase I dose intensification
10www.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 11
NOAEL
>10-fold
therapeutic
dose
Species dose
(mg / kg)
Human
equivalent
dose (mg)*
Ratio to
Expected
Therapeutic
Dose
Cohort 1 0 0 N/A
Cohort 2 12.5 125 1
Cohort 3 125 1250 10
Cohort 4 225 2250 18
Cohort 1 0 0
Cohort 2 4.2 125 1
Cohort 3 42 1250 10
Cohort 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 12
• 5-FU (Efudex)
• Doxorubicin (Adriamycin)
• Temozolomide (Temodar)
• Cetuximab (Erbitux)
• Gefitinib (Iressa)
• Erlotinib (Tarceva)
• Trastuzumab (Herceptin)
• Lapatinib (Tykerb)
• Vemurafenib (Zelboraf)
• Ibrutinib (Imbruvica)
• Bortezomib (Velcade)
13. SpecificApoptosis
• 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
Apoptosis:
www.oncoceutics.com 13
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%
50%
100%
0 50 100
Survival
Days
Control TIC10 bev TIC10 + bev
BeforeRx1week
Vehicle ONC201
ONC201 + bevONC201 bevVehicle
ONC201 Kills Brain Tumors
www.oncoceutics.com
Allen and El-Deiry
et al
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15. 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
16. SpecificApoptosis
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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17. www.oncoceutics.com
SpecificApoptosis
• 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.
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• 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
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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
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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
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
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
21www.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
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