Oncolytics Biotech, Inc.
Technology Changing Life
Dr. Brad Thompson, COB, President and CEO 2008 Photo of Dr Matt Coffey - COO
Photograph by: Gavin Young, Calgary Herald
A Novel Approach to Cancer Therapeutics Oncolytics Biotech is a biotechnology company focused on the development of oncolytic viruses as potential therapeutics for use in a broad range of cancers. The Company is conducting clinical studies using REOLYSIN®, its proprietary formulation of the human reovirus, in some of the most prevalent forms of the disease including lung, colorectal and pancreatic cancers. Oncolytics' clinical program includes a number of human trials at a variety of stages including a Phase III trial in head and neck cancers. The Company has advanced its product manufacturing and intellectual property initiatives in parallel with its clinical development program to support development of a commercial product.
See the official company website for the most current information. www.oncolyticsbiotech.com
CURRENT SUMMARY - March 9th 2014
Expanding Clinical Program
o Lead product is REOLYSIN®, a broadly active novel cancer therapy
o Ongoing clinical trials include seven randomized studies:
o Enrollment complete randomized international study (REO 018) of REOLYSIN® in combination with carboplatin and
paclitaxel in platinum- refractory recurrent head and neck cancer patients – 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 – breast, non-small cell lung, colorectal, prostate, pancreatic
and ovarian cancers
o Strong Intellectual Property Portfolio
o More than 370 patents issued worldwide
o Manufacturing at Commercial Scale - 100L cGMP completed, commercial manufacturing agreement in place
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, intratumoral and intrathecal injection
Mechanism of Action:
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 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
KEY UPCOMING EVENTS
- Results from the NCI sponsored PH II Pancreatic Cancer trial ... Principal Investigator: Tanois Bekaii-Saab:
- Now only waiting for Mets Only Arm of the Phase III H&N : PFS data from the first 160 patients - REO 018, the Phase III SCCHN Trial data now separated into two distinct sub groups... "local recurrent disease, with or without metastases, and patients with distal metastases" - >Recruiting completed in the US, Canada, Belgium, UK. Italy, Spain, and Russia. See November 21 2013 press release describing preliminary results of the first sub group. See Sept 12 2012 press release regarding the analysis of unblinded data from the first 80 patients. "The Company has consulted with its principal investigators and the independent statistician for the study, and, on September 10, 2012, met with the U.S. Food and Drug Administration in Washington, D.C. Based on these discussions, the Company plans to expand enrollment in the first stage of the study to include 160 patients, all of whom have now been enrolled. Oncolytics intends to treat this expanded first stage of the REO 018 clinical trial as a separate supportive study to a planned registration study that will be similar to, and take the place of, the original second stage of the REO 018 clinical trial."
- Principal Investigators Jan Vermorken - Belgium Dr Kevin Harrington - UK , Dr. James A Bonner - US
Publication of data for the PH I/II Ovarian cancer trial also sponsored by the NCI and conducted by Principal Investigator Dr. David Cohn
- 31 human clinical trials running or concluded
- Conducting multiple Phase I/II, Phase II REOLYSIN clinical trials in the United Kingdom and the United States and one Phase III running at 58 Sites in 10 Countries.
- Positive interim and final data emerging including clinical responses in lung, liver and nodal metastatic disease
- Collaborative agreements with the National Cancer Institute of the US and the NCIC-CTG Canada, the University of Leeds, and the Cancer Therapy & Research Center at the University of Texas Health Science Center in the U.S. to conduct multiple clinical trials.
- The Gynecologic Oncology Group (GOG) is conducting a randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN® in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer (GOG186H).
- The Children's Oncology Group (COG) is conducting a Phase I trial of REOLYSIN® in combination with cyclophosphamide in pediatric patients with relapsed or refractory solid tumors.
- Strong IP position , Over 300 Patents Worldwide including 34 US Patents - US Patents can be found at this link.
- Experienced management team and board of directors
The ubiquitous reovirus
Reovirus, an acronym for Respiratory Enteric Orphan virus, is generally believed to inhabit the respiratory and bowel systems in humans. Reovirus is found naturally in sewage and water supplies. By age 12, half of all children show evidence of reovirus exposure and by adulthood, most people have been exposed. However, the disease is non-pathogenic, meaning there are typically no symptoms from infections. The link to its cancer-killing ability was established after the reovirus was discovered to reproduce well in various cancer cell lines.
Using improved microscope technology, a team including Purdue's Timothy S. Baker and a colleague at Harvard has determined the structure of a reovirus (short for "respiratory enteric orphan" virus) down to the 7.6-angstrom scale, better than twice the 18-angstrom resolution previously available. http://www.purdue.edu/UNS/html4ever/031215.Baker.reovirus.html
Synchrotron radiation is the only tool available for the determination of very large molecular structures at high resolution such as the reovirus core. One of the largest structures solved to-date has been reported from work carried out at MacCHESS by Karin Reinish in the Harrison group at Harvard. The reovirus core is a macromolecular assembly with a molecular mass of 52 million. The core synthesizes, modifies, and exports viral messenger RNA. The core contains five of the eight proteins that make up a complete virion and is about 700 Angstroms in diameter. They crystallize in a centered cubic space group with unit cell dimensions of 1255 Angstrom with crystal growth requiring 9 to 12 months. Using the CHESS F1 facility, one of the two Biosafety Level 2 facilities in the US, scientists have been able to "see" into the three-dimensional structure of the core using the tools of x-ray crystallography.
The reovirus core particle shows the subunits in different colors. There are 120 copies of the part in red that forms the shell and that packages the RNA. This part defines the symmetry and size of the particle. Other subunits, shown in yellow, green and white stabilize the shell. The blue parts form turret-like structures around the fivefold axes that exports mature mRNA into the cytoplasm of the infected cell.
is a proprietary variant of the human reovirus that acts primarily as a direct cytotoxic agent. Reovirus is naturally occurring (not genetically engineered) and has been demonstrated to replicate specifically in tumour cells bearing an activated Ras pathway, leaving healthy normal cells intact. At least two thirds of carcinomas and more than 90% of metastatic disease has Ras involvement.
Mechanism of Action
The reovirus, or Respiratory Enteric Orphan virus, has been demonstrated to replicate specifically in tumor cells that have a constitutively activated Ras pathway. Activating mutations of Ras and mutations along the Ras pathway occur in approximately two-thirds of all tumors. Tumors bearing an activated Ras pathway are deficient in their ability to activate an anti-viral response mediated by the host cellular protein, PKR. Since PKR is responsible for preventing reovirus replication, tumor cells that lack the activity of PKR are susceptible to reovirus infection and eventual cell death. As normal cells do not possess Ras activation, these cells are able to thwart reovirus infection by the activity of PKR. In a tumor cell with an activated Ras pathway, the reovirus is able to freely replicate and kill the host tumor cell. Progeny virus particles are then able to infect and kill surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until there are no longer any tumor cells carrying an activated Ras pathway available. The Company's technologies are based on discoveries made in the 1990s in the Department of Microbiology and Infectious Diseases at the University of Calgary. The potential products are being developed using the naturally occurring reovirus for treatment of cancers in humans.
The KRAS Opportunity
In mid-2009, the U.S. FDA approved revisions to labeling of the epidermal growth factor receptor (EGFR) class of antibodies, indicating that colorectal patients who have KRAS mutations in their tumours do not respond to EGFR-inhibiting antibodies and that the use of this class of pharmaceuticals is not recommended for these patients.
REOLYSIN, Oncolytics' proprietary isolate of the reovirus, preferentially replicates in cancer cells that have an activated RAS pathway. Approximately two-thirds of all cancers have an activated RAS pathway, including most metastatic disease. A large number of mutations, including mutations in EGFR, Her2 or KRAS along the RAS pathway lead to RAS pathway activation. A significant clinical opportunity for REOLYSIN is in the treatment of patients with metastatic cancers who have a mutated KRAS gene and are unlikely to respond to treatment with anit-EGFR monoclonal antibodies.
Current Clinical Trials Roadmap
Company published list by Trial Number http://www.oncolyticsbiotech.com/clinical.html
List of US based clinical trials on the official ClinicalTrials.gov website...Search Term: Reolysin
List of EU based clinical trials on the official EU .... https://www.clinicaltrialsregister.eu/ctr-search/search?query=reovirus
Key Published Scientific Data
Links collected here on the company website
Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells by Patrick Lee's lab published March 17, 2009 in Mol Therapy
DAILY and WEEKLY Stock Charts
| Trading Data || Share Structure |
| Exchange Symbol: || TSX: ONC || Estimated As at Jun, 2012 |
| || NASDAQ: ONCY || Outstanding: || 76.6 million |
| || || |
***Cash On Hand Reported to be approx CAD $31.25 Mil on June 30th, 2012 including the bought deal of CAD $18+Mil conversion announced in Feb 2012. Monthly Burn Rate has increased to $3.1 Mil - From Q2 2012 6mo Income Statement. Current and Past Financials can be found by clicking here!
- All numbers are stated in Canadian Dollars
Curing Cancer? Patrick Lee's Path to the Reovirus Treatment
by Paul Thagard from the Philosophy Department of Waterloo in 2002
Dalhousie virologist Patrick Lee: