2. Forward Looking Statements
Today’s 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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3. Oncolytics Overview
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•
•
Expanding Clinical Program
®
• Lead product is REOLYSIN , a broadly active novel cancer therapy
• Ongoing clinical trials include seven randomized studies:
• Enrollment complete in randomized international study (REO 018)
of REOLYSIN® with carboplatin and paclitaxel in platinumrefractory recurrent head and neck cancer patients − the supportive
study to a planned Phase III registration study in this indication
• Six sponsored Phase II studies announced or ongoing in the U.S.
and Canada – breast, non-small cell lung, colorectal, prostate,
pancreatic and ovarian cancers
Strong Intellectual Property Portfolio
• More than 370 patents issued worldwide
Manufacturing at Commercial Scale
• 100L cGMP completed, commercial manufacturing agreement in place
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4. REOLYSIN® Overview
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REOLYSIN® is a proprietary isolate of the reovirus
•
Reovirus is a replication competent virus and is considered safe to humans
•
REOLYSIN® has been safely administered to patients via intravenous,
intratumoural and intrathecal injection
•
Mechanism of Action:
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In Ras-activated cells, one of the key cellular defence mechanisms against doublestranded 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 REOLYSIN®’s activity and specificity
Reovirus oncolysis is seen in cancer cells with constitute Ras pathway activation;
susceptible cancer cells therefore include those with either:
• EGFR overexpression or mutation1; or
• Ras mutation, which includes Kras mutation2
Both of these mutations lead to activation of the Ras pathway
1
Evidence that the epidemal growth factor receptor on host cells confers reovirus infection efficiency. Strong et al. Virology 1993; 197(1): 405
2
The molecular basis of viral oncolysis: usurpation of the Ras signalling pathway by reovirus. Strong et al. EMBO J 1998; 17(12): 3351
4
5. REOLYSIN Mechanism of Action
®
Normal Cells
REOLYSIN®
infects both tumour
cells and normal,
healthy cells
REOLYSIN®
administered to
patients via IV
REOLYSIN®
is a virus whose
replication is
stopped in a nonRas-activated cell
Healthy cell
remains
undamaged
Ras-Activated Cells
REOLYSIN®
infects both tumour
cells and normal,
healthy cells
REOLYSIN®
replicates in Rasactivated tumour
cells
5
Tumour cells
rupture to release
progeny virus
Replicated viruses
repeat cell lysis cycle in
nearby tumour cells
6. REO 013: REOLYSIN®-Induced Tumour Responses
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•
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Image shows positive (red staining)
for reovirus in the metastatic lesions
(yellow 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 tumour lesions of the liver
In addition, two of the ten patients
had complete tumour necrosis
This demonstrates that REOLYSIN®
specifically accesses and replicates in
metastatic colorectal cancer when
delivered as a monotherapy
6
7. Market for Ras Pathway-Mediated Cancers
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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. REOLYSIN® Clinical Program Overview
REOLYSIN® has been utilized in studies in over 620 patients
In total, nearly thirty ongoing or completed clinical trials including:
•
•
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
Nine single-arm studies in the following indications:
•
Phase II trials:
•
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Company sponsored: pancreatic cancer, non-small cell lung cancer, head and neck
carcinoma, metastatic melanoma and squamous cell carcinoma
Phase I trials:
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Company sponsored: colorectal cancer and advanced malignancies
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Investigator sponsored: multiple myeloma and relapsed or refractory solid tumours
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9. Ongoing Randomized Studies of REOLYSIN®
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 +
Avastin®
100
NCIC
IND 211: Non-Small Cell Lung
Cancer
Docetaxel or
pemetrexed
150
NCIC
IND 213: Breast Cancer
Paclitaxel
100
NCIC
Preclinical
9
Phase I
Phase II
Phase III
Sponsor
10. Phase III (Pivotal) Program for REOLYSIN
in Squamous Cell Head and Neck Cancers
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In Q3 2012, Oncolytics completed enrollment in REO 018, a randomized, two stage, two-arm,
double-blind, multi-center trial examining REOLYSIN® in combination with carboplatin and
paclitaxel in taxane-naïve patients with platinum-refractory recurrent head and neck cancers
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EGOC performance status (0-1 versus 2)
Time of progression/relapse after prior platinum-based chemotherapy
Disease location (patients with locally recurrent disease, with or without distal metastases, versus
patient with metastatic disease only)
REO 018 Endpoints:
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The study was approved and run in fourteen countries in North America and Europe
Patients in the REO 018 study were stratified for:
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®
Primary Endpoint: Overall Survival (OS)
Secondary Endpoints: Progression-Free Survival (PFS), best response and tumour-specific response
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.
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11. REO 018: Tumour-Specific Response Data
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Data announced December 13, 2012
Endpoint examines initial percentage tumour changes between baseline
and first post treatment scans in all patients, differentiating between
loco-regional tumours and metastatic tumours
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This is a measure of rate or velocity of response, not magnitude of response
The endpoint was introduced to determine if REOLYSIN adds tumour
specific differential activity in metastatic and loco-regional disease in a
randomized setting
®
Of the total 105 patients with evaluable metastatic tumours, 86% (n=50)
of those in the test, and 67% (n=55) in the control arm, arm had tumour
stabilization (0% growth) or shrinkage
•
This is a statistically significant difference, with a p-value of 0.025
11
12. REO 018: Percentage Change in Metastatic Lesions
at First Post-Treatment Scan (Control vs. Test)
100.00%
80.00%
Percent Change (Target Lesions)
60.00%
40.00%
20.00%
0.00%
Control
0
0.1
0.2
0.3
0.4
0.5
-20.00%
-40.00%
-60.00%
-80.00%
-100.00%
p=0.03
12
0.6
0.7
0.8
0.9
1
Test
13. REO 018: Top-Line Efficacy Data
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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
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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)
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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 REOLYSIN® 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)
14. REO 018: Top-Line Safety Data
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Data announced November 21, 2013 for all 167 patients enrolled
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REOLYSIN® was safe and well-tolerated by patients
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Patients on the test arm of the study experienced a higher incidence
of flu-like symptoms consistent with earlier clinical trials of
REOLYSIN® and treatment with a virus
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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)
•
On this basis, Oncolytics intends to explore the potential chemoprotective
and neuroprotective properties of REOLYSIN® in future clinical studies
15. REO 016: Non-Small Cell Lung Cancer
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Single-arm (up to 36 patients), open-label, two-stage U.S. Phase II
study of intravenously-administered REOLYSIN® in combination
with carboplatin and paclitaxel
For non-small cell lung cancer (NSCLC) patients who have been prescreened for Kras and EGFR mutation status
• 15-20% of NSCLC is Kras-mutated, while up to 50% is EGFRmutated or -overexpressed, all of which cause Ras pathway
activation
• First-line therapy study, i.e. patients will be offered REOLYSIN® in
combination with carboplatin and 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
®
REOLYSIN Efficacy
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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
18. REO 021: Squamous Cell Carcinoma (SCC) of the Lungs
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Single-arm (up to 36 patients), open-label US Phase II study of
intravenously-administered REOLYSIN® 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
20
Post-Cycle 4
21. Randomized Canadian Studies of REOLYSIN®
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Patients are currently being enrolled in four randomized Phase II studies
in Canada:
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IND 209: Intravenous Administration of REOLYSIN® in Combination with
Docetaxel for Patients with Recurrent or Metastatic Castration Resistant
Prostate Cancer
IND 210: Intravenous Administration with REOLYSIN® in Combination with
FOLFOX-6 Plus Avastin® versus FOLFOX-6 Plus Avastin® Alone in Patients
with Advanced or Metastatic Colorectal Cancer
IND 211: Intravenous Administration of REOLYSIN® in Combination with
Docetaxel or Pemetrexed for Patients with Previously-Treated Advanced or
Metastatic Non-Small Cell Lung Cancer
IND 213: Intravenous Administration of REOLYSIN® in Combination with
Paclitaxel for Patients with Advanced or Metastatic Breast Cancer
All four studies are sponsored by the National Cancer Institute of
Canada’s Clinical Trials Group (NCIC CTG)
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22. Randomized U.S. Studies of REOLYSIN®
•
Patients are currently being enrolled in two randomized Phase II
studies in the United States:
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•
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OSU-10045: Intravenous Administration of REOLYSIN® in Combination
with Paclitaxel and Carboplatin for Patients with Metastatic Pancreatic
Cancer
GOG-0186H: Intravenous Administration of REOLYSIN® 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. REOLYSIN® and Safety
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More than 620 patients treated, more than 530 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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More than 370 patents issued worldwide, including 51 US and 16
Canadian
Reovirus issue patent claims cover:
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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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25. Manufacturing
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Now produced at 100L under cGMP with final formulation
•
Commercial manufacturing agreement with SAFC in place
25
27. Oncolytics Summary
•
•
•
Expanding Clinical Program
®
• Lead product is REOLYSIN , a broadly active novel cancer therapy
• Ongoing clinical trials include seven randomized studies:
• Enrollment complete in randomized international study (REO 018)
of REOLYSIN® with carboplatin and paclitaxel in platinumrefractory recurrent head and neck cancer patients − the supportive
study to a planned Phase III registration study in this indication
• Six sponsored Phase II studies announced or ongoing in the U.S.
and Canada – breast, non-small cell lung, colorectal, prostate,
pancreatic and ovarian cancers
Strong Intellectual Property Portfolio
• More than 370 patents issued worldwide
Manufacturing at Commercial Scale
• 100L cGMP completed, commercial manufacturing agreement in place
27
