2. Forward Looking Statements
This presentation contains certain forward looking statements relating to the
companyâs financial results, business prospects and the development and
commercialization of REOLYSINÂŽ, a therapeutic reovirus. These statements are
based on managementâs 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 companyâs 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 BiotechÂŽ 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 companyâs 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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3. Oncolytics Overview
o
o
o
Expanding Clinical Program
o Lead product is REOLYSINÂŽ, a broadly active novel cancer therapy
o Ongoing clinical trials include seven randomized studies:
o Enrollment complete randomized international study (REO 018) of
REOLYSINÂŽ in combination with carboplatin and paclitaxel in platinumrefractory recurrent head and neck cancer patients â the supportive
study to a planned Phase III registration study in this indication
o Six sponsored Phase II studies announced or ongoing in the US and
Canada â breast, non-small cell lung, colorectal, prostate, pancreatic
and ovarian cancers
Strong Intellectual Property Portfolio
o More than 370 patents issued worldwide
Manufacturing at Commercial Scale
o 100L cGMP completed, commercial manufacturing agreement in place
3
4. REOLYSINÂŽ Overview
REOLYSINÂŽ is a proprietary isolate of the reovirus
o
o
Reovirus is a replication competent virus and is considered safe to humans
REOLYSINÂŽ has been safely administered to patients via intravenous,
intratumoral and intrathecal injection
Mechanism of Action:
o
o
o
o
o
In Ras-activated cells, one of the key cellular defence mechanisms against
double-stranded RNA viral infection, Protein Kinase-R (PKR), is deactivated
This specific vulnerability of constitutive Ras-activated cancer cells to the
reovirus is the basis of REOLYSINÂŽâs activity and specificity
Reovirus oncolysis is seen in cancer cells with constitute Ras pathway
activation; susceptible cancer cells therefore include those with either:
o
o
o
1
2
EGFR overexpression or mutation1; or
Ras mutation, which includes Kras mutation2
Both of these mutations lead to activation of the Ras pathway
Evidence that the epidemal growth factor receptor on host cells confers reovirus infection efficiency. Strong et al. Virology 1993; 197(1): 405
The molecular basis of viral oncolysis: usurpation of the Ras signalling pathway by reovirus. Strong et al. EMBO J 1998; 17(12): 3351
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5. REOLYSINÂŽ Mechanism of Action
Normal Cells
REOLYSINÂŽ
administered to
patients via IV
REOLYSINÂŽ
infects both tumor
cells and normal,
healthy cells
REOLYSINÂŽ
Healthy cell
is a virus whose
remains
replication is
undamaged
stopped in a nonRas-activated cell
Ras-Activated Cells
REOLYSINÂŽ
infects both tumor
cells and normal,
healthy cells
REOLYSINÂŽ
replicates in Rasactivated tumor
cells
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Replicated viruses
Tumor cells
rupture to release repeat cell lysis cycle
in nearby tumor cells
progeny virus
6. REO 013: REOLYSINÂŽ Induced Tumour Response
o
o
o
o
Image shows positive (red
staining) for reovirus in the
metastatic lesions (blue arrow)
and negative for reovirus in the
normal cells (red arrow)
Nine out of ten patients showed
the same pattern, i.e. targeted
delivery to metastatic tumor
lesions of the liver
In addition, two of the ten
patients had complete tumor
necrosis
This demonstrates that
REOLYSINÂŽ specifically accesses
and replicates in metastatic
colorectal cancer when delivered
as a monotherapy
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7. Market for Ras Pathway Mediated Cancers
o
o
o
Estimated global cancer market was $77 billion in 2011; this is
expected to rise to $105 billion in 2016
At least five million new patients per year are expected to
develop cancers with a Ras pathway involvement
In the developed world alone, at least 2.6 million patients per
year die of cancers that have metastasized
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8. REOLYSINÂŽ Clinical Program Overview
REOLYSINÂŽ has been utilized in studies in over 1,000 patients
In total, nearly thirty ongoing or completed clinical trials including:
o Seven randomized Phase II and Phase III clinical trials, including Phase III
head and neck cancer and Phase II trials for ovarian, pancreatic, prostate,
colorectal, non-small cell lung and breast cancers
o Nine single arm studies in the following indications:
o Phase II trials:
o
o
Company sponsored: pancreatic cancer, non-small cell lung cancer, head and neck carcinoma,
metastatic melanoma and squamous cell carcinoma
Phase I trials:
o
o
Company sponsored: colorectal cancer and advanced malignancies
Investigator sponsored: multiple myeloma and relapsed or refractory solid tumors
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9. REOLYSINÂŽ: Randomized Pipeline
Indication
Combination
Therapy
n
REO 018: Head & Neck Cancer
Carboplatin +
paclitaxel
167
n/a
GOG-0186H: Ovarian, Fallopian Tube
& Primary Peritoneal Cancers
Paclitaxel
110
NCI/
GOG
OSU-10045: Pancreatic Cancer
Carboplatin +
paclitaxel
70
NCI
IND 209: Prostate Cancer
Docetaxel
80
NCIC
IND 210: Colorectal Cancer
FOLFOX-6 +
AvastinÂŽ
100
NCIC
IND 211: Non-Small Cell Lung Cancer
Docetaxel or
pemetrexed
150
NCIC
IND 213: Breast Cancer
Paclitaxel
100
NCIC
Preclinical
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Phase I
Phase II
Phase III
Sponsor
10. Phase III (Pivotal) Program for REOLYSINÂŽ
in Squamous Cell Head & Neck Cancers
o
In Q3 2012, Oncolytics completed enrollment in REO 018, a randomized, two stage, two-arm,
double-blind, multi-center trial examining REOLYSINÂŽ in combination with carboplatin and
paclitaxel in taxane-naĂŻve patients with platinum-refractory recurrent head and neck cancers
o
o
The study was approved and run in fourteen countries in North America and Europe
Patients in the REO 018 study were stratified for:
o
ECOG performance status (0-1 versus 2)
o
Time of progression/relapse after prior platinum-based chemotherapy
o
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Disease location (patients with locally recurrent disease, with or without distal metastases, versus patients
with metastatic disease only)
REO 018 Endpoints:
o
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Secondary Endpoints: Progression-Free Survival (PFS), best response and tumour-specific response
o
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Primary Endpoint: Overall Survival (OS)
Pharmacodynamic Endpoints: Tumour Ras pathway status and HPV status
The Company intends to treat REO 018 as a separate supportive study to a planned randomized,
follow-on international Phase III head and neck registration study in patients with loco-regional
head and neck cancer
10
11. REO 018: Tumor Specific Response Data
o
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Data announced December 13, 2012
Endpoint examines initial percentage tumor changes between
baseline and first post treatment scans in all patients,
differentiating between loco-regional tumours and metastatic
tumours
o
o
o
This is a measure of rate or velocity of response, not magnitude of
response
The endpoint was introduced to determine if REOLYSINÂŽ adds
tumor specific differential activity in metastatic and loco-regional
disease in a randomized setting
Of the total 105 patients with evaluable metastatic tumors, 86%
(n=50) of those in the test, and 67% (n=55) in the control arm, arm
had tumor stabilization (0% growth) or shrinkage
o
This is a statistically significant difference, with a p-value of 0.025
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12. REO 018: Percentage Change in Metastatic Lesions at
First Post-Treatment Scan (Control vs. Test)
100.00%
Percent Change (Target Lesions)
80.00%
60.00%
40.00%
20.00%
Control
0.00%
0
0.1
0.2
0.3
0.4
0.5
0.6
-20.00%
-40.00%
-60.00%
-80.00%
-100.00%
p=0.03
12
0.7
0.8
0.9
1
Test
13. REO 018: Top-Line Efficacy Data
o
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Data announced November 21, 2013
An analysis was performed on an intent-to-treat basis of the 118
patients with loco-regional disease, with or without metastases
o
o
Patients in the test arm (n=62) showed a median PFS of 94 days
(13.4 weeks), versus 50 days (7.1 weeks) in the control arm (n=56)
o
o
At the time of reporting, there had not been a sufficient number of
events to conduct a survival analysis of patients in the metastatic-only
group
Patients who received REOLYSINÂŽ had increased benefit through five
cycles of therapy
Of 88 patients who did not receive additional therapy following
discontinuation of study treatment, those in the test arm (n=50)
showed a median OS of 150 days (21.4 weeks), versus 115 days
(16.4 weeks) in the control arm (n=38)
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14. REO 018: Top-Line Safety Data
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Data announced November 21, 2013 for all 167 patients enrolled
REOLYSINÂŽ was safe and well-tolerated by patients
Patients on the test arm of the study experienced a higher
incidence of flu-like symptoms consistent with earlier clinical trials
of REOLYSINÂŽ and treatment with a virus
o
o
Most commonly mild fever, chills, nausea and diarrhea
Fewer patients required dose reductions of paclitaxel due to
neuropathy or neurotoxicity on the test arm than the control arm
(zero in the test arm versus six in the control; p=0.028)
o
On this basis, Oncolytics intends to explore the potential
chemoprotective and neuroprotective properties of REOLYSINÂŽ in
future clinical studies
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15. REO 016: Non-Small Cell Lung Cancer
o
o
Single-arm (up to 36 patients), open-label, two-stage US
Phase II study of intravenously-administered REOLYSINÂŽ in
combination with carboplatin and paclitaxel
For non-small cell lung cancer (NSCLC) patients who have
been pre-screened for Kras and EGFR mutation status
o
o
15-20% of NSCLC is Kras mutated, while up to 50% is EGFR mutated or
overexpressed, all of which cause Ras pathway activation
First-line therapy study, i.e. patients will be offered REOLYSINÂŽ /
carboplatin / paclitaxel instead of standard of care if they are Kras or
EGFR mutated or EGFR overexpressed
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16. REO 016: Biomarker Correlations with
REOLYSINÂŽ Efficacy
o
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Of 36 evaluable patients, all of whom were Stage IV on
entry, 89% exhibited SD or better (11 PR, 21 SD and 4 PD by
RECIST)
20 of these 36 patients (56%) had one year or more of
survival
Of 24 patients with at least an EGFR mutation or
amplification, 16 (66.7%) had one year or more of survival
Of 13 patients with only an EGFR mutation or amplification,
9 (69.2%) had one year or more of survival
Of 4 patients with BRAF and EGFR amplifications, 4 (100%)
had one year or more of survival
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18. REO 021: Squamous Cell Carcinoma of
the Lungs
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o
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Single-arm (up to 36 patients), open-label US Phase II
study of intravenously-administered REOLYSINÂŽ in
combination with carboplatin and paclitaxel
Final results in 25 evaluable patients (all with
metastatic disease) demonstrated that 92% (23
patients) exhibited overall tumour shrinkage, with
mean shrinkage of 32.7%
Of the 25 evaluable patients who received more than
one cycle of therapy, 10 (40%) showed partial
responses by RECIST, and a further 12 (48%) showed
stable disease by RECIST, for a disease control rate (CR
+ PR + SD) of 92%
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20. REO 021: Partial Response in Lung
Right Upper Lung Mass (8.3 cm)
Right Upper Lung Mass (4.1 cm)
Right Upper Lung Mass (3.6 cm)
Right Pleural Met (2.2 cm)
Right Pleural Met (0.8 cm)
Right Pleural Met (0.4 cm)
Pre-Treatment
Post-Cycle 2
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Post-Cycle 4
21. Randomized Canadian Studies of REOLYSINÂŽ
o
Patients are currently being enrolled in four randomized Phase II
studies in Canada:
o
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o
o
o
IND 209: Intravenous Administration of REOLYSINÂŽ in Combination
with Docetaxel for Patients with Recurrent or Metastatic Castration
Resistant Prostate Cancer
IND 210: Intravenous Administration of REOLYSINÂŽ in Combination
with FOLFOX-6 Plus AvastinÂŽ versus FOLFOX-6 Plus AvastinÂŽ Alone in
Patients with Advanced or Metastatic Colorectal Cancer
IND 211: Intravenous Administration of REOLYSINÂŽ in Combination
with Docetaxel or Pemetrexed for Patients with Previously-Treated
Advanced or Metastatic Non-Small Cell Lung Cancer
IND 213: Intravenous Administration of REOLYSINÂŽ in Combination
with Paclitaxel for Patients with Advanced or Metastatic Breast Cancer
All four studies are sponsored by the National Cancer Institute of
Canadaâs Clinical Trials Group (NCIC CTG)
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22. Randomized U.S. Studies of REOLYSINÂŽ
o
Patients are currently being enrolled in two
randomized Phase II studies in the United States:
o
o
o
OSU-10045: Intravenous Administration of REOLYSINÂŽ in
Combination with Paclitaxel and Carboplatin for Patients
with Metastatic Pancreatic Cancer
GOG-0186H: Intravenous Administration of REOLYSINÂŽ in
Combination with Paclitaxel for Patients with Persistent or
Recurrent Ovarian, Fallopian Tube or Primary Peritoneal
Cancer
Both studies are sponsored by the U.S. National Cancer
Institute (NCI), with GOG-0186H being conducted by
the Gynecologic Oncology Group (GOG)
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23. REOLYSINÂŽ and Safety
o
o
o
o
o
More than 1,000 patients treated, more than 900 intravenously at
doses up to 3x1010 TCID50 daily
No maximum tolerated dose (MTD) reached to date
Monotherapy toxicities have generally been mild (grade 1 or 2) and
included chills, fever, headache, cough, myalgia, runny nose, sore
throat, fatigue and grade 1 or 2 lymphopenia and neutropenia
Transient grade 3 and 4 toxicities included lymphopenia and
neutropenia
These symptoms were more frequently observed from day 2 of
treatment and usually lasted less than 6 hours
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24. Intellectual Property
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o
More than 370 patents issued worldwide, including 51 US
and 16 Canadian
Reovirus issue patent claims cover:
o
o
o
o
o
o
Compositions of matter comprising reovirus
Pharmaceutical use of reoviruses to treat neoplasia and cellular
proliferative diseases
Combination therapy with radiation, chemotherapy and/or
immune suppressants
Methods for manufacturing reovirus and screening for
susceptibility to reovirus
Pharmaceutical use of reoviruses in transplantation procedures
Approximately 235 pending applications worldwide
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27. Oncolytics Summary
o
o
o
Expanding Clinical Program
o Lead product is REOLYSINÂŽ, a broadly active novel cancer therapy
o Ongoing clinical trials include seven randomized studies:
o Enrollment complete randomized international study (REO 018) of
REOLYSINÂŽ in combination with carboplatin and paclitaxel in platinumrefractory recurrent head and neck cancer patients â the supportive
study to a planned Phase III registration study in this indication
o Six sponsored Phase II studies announced or ongoing in the US and
Canada â breast, non-small cell lung, colorectal, prostate, pancreatic
and ovarian cancers
Strong Intellectual Property Portfolio
o More than 370 patents issued worldwide
Manufacturing at Commercial Scale
o 100L cGMP completed, commercial manufacturing agreement in place
27
