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Forward Looking Statements
This presentation contains certain forward looking statements relating to the company’s financial results, business prospects and the development and commercialization of REOLYSIN®, a therapeutic reovirus. These statements are based on management’s current expectations and beliefs and are subject to a number of factors which involve known and unknown risks, delays, uncertainties and other factors not under the company’s control which may cause actual results, performance or achievements of the company to be materially different from the results, performance or other expectations implied by these forward looking statements.
In any forward looking statement in which Oncolytics Biotech® Inc. expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. These factors include results of current or pending clinical trials, risks associated with intellectual property protection, financial projections, market projections, actions by the FDA/HPB/MHRA and those other factors detailed in the company’s filings with SEDAR and the Securities and Exchange Commission. Oncolytics does not undertake an obligation to update the forward looking statements, except as required by applicable laws.
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Oncolytics Overview
Conducted 30+ clinical studies in 13 indications
400+ issued patents and 235 pending applications worldwide
1,100+ patients treated; strong safety profile
Developing REOLYSIN®(oncolytic virus) as a cancer therapeutic
$32.1 million cash as at the end of Q2, 2015
Manufacturingat commercial scale100L cGMP completed
What is REOLYSIN®?
Proprietary isolate of the reovirus
Widely found
Non-pathogenic
Widespread human exposure
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REOLYSIN® Mechanism of Action
REOLYSIN®infects both tumour cellsand normal healthy cells
REOLYSIN® does not replicate in cells that are not Ras activated
Healthy cells remain undamagedREOLYSIN®
Administered to patients
PRE-SCREENEDfor RAS, EGFR,
BRAF and others
Normal Cells
REOLYSIN® infects both tumour cells and normal healthy cells
REOLYSIN® replicates in Ras-activated tumour cells
Tumour cells then rupture to release progeny virus
Progeny viruses repeat cell infection cycle in nearby tumour cells
Ras–Activated Cells
Productively infected cells upregulate interferon and others, including PD-1 and PD-L1, and induce an anti-tumour specific immune response mediated by NK and T cells
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REOLYSIN® and SafetyGeneral Safety
1,100+ patients treated, 1,000+ intravenously
No MTD reached
Safety profile confirmed in a randomized setting
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Monotherapy Safety
Mild toxicities (grade 1 or 2) including
Transient grade 3 and 4 toxicities included lymphopenia or neutropenia – symptoms usually last < 6 hours
• Chills• Fever• Headache
• Cough• Myalgia• Runny nose
• Sore throat• Fatigue• Lymphopenia or neutropenia
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REOLYSIN® Clinical Program
GLIOMA
PROSTATE
OVARIAN
COLORECTAL
LUNG
PANCREATIC
MYELOMA
MELANOMA
HEAD AND NECK
BREAST
BLADDER
Indication Studies
Ongoing Study Completed Study
REO 001 Phase I
REO 007Phase I/II
REO 002 Phase I
REO 003 Phase I/II
REO 004 Phase I
REO 005 Phase I
NCI (MAYO –MC0672 )Phase II
REO 009Phase I
REO 011Phase I/II
MAY0 (MC-1472)Phase I
REO 015Phase II
REO 017Phase I/II
REO 018Phase III
REO 020Phase II
REO 022Phase II
NCI (GOG-0186H)Phase II
REO 013 Brain Phase I
NCI 8601Phase II
IND 209Phase II
IND 210Phase II
NCI (OSU-07022)Phase I/II
IND 213Phase II
NCI (OSU-11148)Phase I
NCI 9603Translational
REO 014 Phase II
REO 016Phase II
REO 021Phase II
IND 211Phase II
REO 008 Phase II
NCI (COG-ADVL1014)Phase I Orphan Status
Orphan Status
Orphan Status
REO 019Run-In Study
REOLYSIN® AddressableMarket
Breast140,514
Ovarian12,774
Soft tissue7,158
Brain13,710
Head & Neck27,468
Pancreas29,376
Prostate132,480
Melanoma44,322
Myeloma16,110
Colon & Rectum79,620
Lung & Bronchus132,720
1,000,000+ new U.S. cases a year in studied indications,of which REOLYSIN® conservatively addresses 60%
Source: American Cancer Society – Cancer Facts and Figures 2015 Estimated New Cases per Indication in the U.S. in 2015
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Orphan Drug DesignationsOrphan Drug Designations obtained for REOLYSIN®:
Potential benefits of Orphan Drug Designation:
A period of market exclusivity (US and EU)
Potential tax credits for certain activities (US)
Eligibility for orphan drug grants (US)
Potential fee waivers and/or reductions (US and EU)
Protocol assistance (EU)
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FDA EMA
• ovarian • primary peritoneal • ovarian
• pancreatic • fallopian tube • pancreatic
• malignant gliomas • gastric
Days after REOLYSIN® administration:
0 3 43 88 167 537
REO 003: REOLYSIN® IntratumouralMonotherapy Anaplastic Astrocytoma
Early Cytotoxic Activity Followed by Late Stage Immune-Mediated
Response Against the Residual Tumour
Viral replication mediated tumour response
Post debulking Immune mediated tumour response
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REO 021: Partial Response in Patient with Squamous Cell Carcinoma of the Lung
Right Upper Lung Mass (8.3 cm)
Pre-Treatment
Right Pleural Met (2.2 cm)
Right Upper Lung Mass (4.1 cm)
Post-Cycle 2
Right Pleural Met (0.8 cm)
Right Upper Lung Mass (3.6 cm)
Post-Cycle 4
Right Pleural Met (0.4 cm)
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REO 018 Head and Neck Cancer: Randomized Tumour-Specific Response Data
First Endpoint: Velocityo 105 patients
o 86% of test arm (n=50) had tumour stabilization or shrinkage
o 67% of control arm (n=55) had tumour stabilization or shrinkage
o p-value 0.025
Second Endpoint: VolumeLoco-regional patients with or without distal metastases
o 23% improvement in test arm vs. control for tumour volume decrease
o p-value 0.076, n=118
Patients with distal metastases only
o 30% improvement in test arm vs. control for tumour volume decrease
o p-value 0.021, n=47
Study demonstrated that REOLYSIN® increased both the magnitude and velocity of tumour shrinkage
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Registration Program for REOLYSIN®
Short-Term: Tumour Reduction Endpoints: Neoadjuvant treatment of muscle-invasive bladder cancer
Neoadjuvant = therapy used prior to a major therapeutic intervention (usually surgery) in order to improve outcome
Next Steps:
IND has been filed to conduct a small “run-in” study assessing histopathological response in muscle invasive bladder cancero REOLYSIN® in combination with gemcitabine and cisplatin
Subject to confirmation of response – proceed to pivotal trial
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Studies demonstrate that REOLYSIN® increases both the magnitude and velocity of tumor shrinkage
Muscle invasive bladder cancer is the only cancer indication in which US regulators have accepted histopathological response as a registration endpoint in a neoadjuvant study to date
Each patient enrolled in the study will be assessable for this endpoint at a maximum of nine weeks after starting treatment
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Why Muscle Invasive Bladder Cancer?
Top-Line Overall Survival (OS) Results: REO 018 (Head and Neck Cancer)
An intent-to-treat analysis of 118 patients with loco-regional disease showed a statistically significant improvement in the OS of the test arm versus that of the control arm1
p=0.0146
hazard ratio=0.5099
1 Overall survival was measured to the median PFS in each arm, censoring any patients who received
post-discontinuation therapy from the date on which they commenced the first of these therapies.
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Top-Line Overall Survival (OS) Results
REO 017 (Pancreatic Cancer) – Comparison with ACCORD 11 and MPACT Studies:
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Days Post Treatment:
0 3 43 88 167 537
REO 003: REOLYSIN® IntratumouralMonotherapy Anaplastic Astrocytoma
Early Cytotoxic Activity Followed by Late Stage Immune-Mediated
Response Against the Residual Tumour
Viral replication mediated tumour response
Post debulking Immune mediated tumour response
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REOLYSIN®: Enhancing Immune Response
REOLYSIN® acts as a selective cytotoxin – killing the tumour cells in which it replicates
We now know that administration of REOLYSIN® also:
Causes the immune system to recognize and kill tumour cells as well
Causes up-regulation of PD-1 and PD-L1
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REOLYSIN®: Immunology & Anti-PD-1 / PD-L1
In some types of cancer (including pancreatic cancer, glioblastoma and metastatic brain lesions), REOLYSIN® has been shown to upregulate PD-1 and PD-L1 (Appendix A)
In cancers with low PD-1 and PD-L1 upregulation, this enhances the activity of checkpoint inhibitors
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Immune Preclinical Research In ovarian cancer models in mice:
Combination of gemcitabine and reovirus type 3 improved overall survival
In melanoma models in mice: Combination of GM-CSF with REOLYSIN® improved overall
survival
In brain cancer models in mice: Combination of a checkpoint inhibitor (anti-PD-1) with
REOLYSIN® improved overall survival
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Enhancing Immune Responses to Improve Overall Survival
Ongoing preclinical and clinical research has led to three clinical programs:
1. Gemcitabine in combination with REOLYSIN® (REO 009 and REO 017);
2. GM-CSF in combination with REOLYSIN® (Mayo (pediatric) and Leeds (adult)); or
3. Checkpoint inhibitors in combination with REOLYSIN® (studies pending)
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Registration Program for REOLYSIN®
Medium-Term: intravenous treatment of advanced gliomas
Long-Term: to be determined upon receipt of data from ongoing single-arm and randomized studies in a range of indications
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Medium-Term – Overall Survival Endpoints A key finding from REO 013 was that REOLYSIN® can cross the blood brain barrier
and subsequently infect and kill tumour in the brain, as well as primary gliomas and metastatic lesions from other primary cancers outside brain
We have completed and initiated four studies of REOLYSIN® in glioma patients:
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• REO 003 – Ph 1/2 local mono-therapy
• REO 007 – Phase 1/2 infusion mono-therapy
• REO 013 – Ph 1 IV prior to surgical resection
• MC1472 – Ph 1 IV combined with GM-CSF -pediatric (ongoing)
Registration Program for REOLYSIN®
Registration Program for REOLYSIN®
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Next Steps A small “run-in” study assessing response in gliomas has been initiated
(Mayo Clinic’s MC1472)
o Pediatric patients being treated with REOLYSIN® in combination with GM-CSF
Second study assessing response in adult patients receiving REOLYSIN® and the standard of care (surgery followed by radiation and temozolomide)
Subject to confirmation of best approach – proceed to pivotal trial
Manufacturing
Now produced at 100L (commercial scale) under cGMP with final formulation
Commercial manufacturing agreement in place with Sigma-Aldrich® Fine Chemicals (SAFC)
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Patent Portfolio More than 400 patents issued
worldwide, including 56 US and 20 Canadian
Reovirus issue patent claims cover:o Compositions of matter comprising reovirus
o Pharmaceutical use of reoviruses to treat neoplasia and cellular proliferative diseases
o Combination therapy with radiation, chemotherapy and/or immune suppressants
o Methods for manufacturing reovirus and screening for susceptibility to reovirus
o Pharmaceutical use of reoviruses in transplantation procedures
Approximately 235 pending applications worldwide
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Market & Capital Data
(allamountsinCAD)
Exchanges NASDAQ:ONCY
TSX:ONC
SharesOutstanding(June30,2015) 117,710,372
Price
OptionsOutstanding(June30,2015) $3.16(weighted
average)
5,531,394
FullyDiluted(June30,2015) 123,241,766
Cash/CashEquivalents(June30,2015) $32.1M
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Investment Highlights
Five ongoing randomized Phase II studies Ovarian, colorectal, non-small cell lung, prostate and breast cancers
Preparing for registration study
Safety data for 1,100+ patients
Strong intellectual portfolio
More than 400 patents worldwide
Manufacturing at commercial scale
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Appendix A: Presence of Reoviral Protein, PD-1 & PD-1 (REO 013b Study)
Case Diagnosis Reoviral Protein PD-L1 PD-1
1 glioblastoma 1+ 2+ 2+
2 adenocarcinoma (colon metastasis) 1+ 2+ 2+
3 glioma, grade 3 1+ 2+ 2+
4 glioma, grade 3 negative 0 1+
5 melanoma metastasis negative 1+ 2+
6 glioblastoma 1+ 2+ 2+
7 glioblastoma negative weak 0
8 glioblastoma 1+ 1+ 2+
9 melanoma metastasis 2+ 3+ 2+
10 (control) adenocarcinoma (breast metastasis) negative 0 0
11 (control) glioblastoma negative 0 0
12 (control) glioblastoma negative 0 0
13 (control) glioblastoma negative 0 0
14 (control) glioblastoma negative 0 0
15 (control) adenocarcinoma (ovarian metastasis) negative 0 weak