Oncolytics Biotech Inc. (ONCY)

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This article is not an easy read. It’s dense with information, and assumes that the reader has an existing understanding of much of the material being covered.

A very brief summary (with the risk of being misleading in its brevity) would be that in a tested cancer cell line where Avastin fails, and reovirus fails; Avastin + reovirus in combination achieves a 90% survival rate. A more detailed summary follows that was posted on April 2, 2010.

From the 850+ member, free, moderated, oncyV2 board at:
http://finance.groups.yahoo.com/group/oncyV2/message/8172

Antiangiogenic cancer therapy with oncolytic virotherapy

Background: Vascular endothelial growth factor (VEGF) is recognized as an essential regulator of both normal and abnormal blood vessel growth. In 1993, it was shown that a monoclonal antibody that targets VEGF can produce a dramatic suppression of tumor growth, and this lead to the development of bevacizumab (Avastin; Genentech - Roche). Rather than saying anti-angiogenic therapies, or VEGF inhibitors, or VEGF165 or VEGF-A inhibitors; I'm just going to say Avastin, although there are now additional drugs (like sorafenib, and sunitinib) that function in a similar way.

In the JCI paper at
http://www.jci.org/articles/view/41431?key=1ec1c381a8cdc1939fa9 , the authors believe that they have demonstrated that Avastin, in combination with systemic delivery of oncolytic viruses under specific timing constraints, leads to substantial regression and cure of established tumors, in mice with normal immune systems. For the model used, they selected a cancer cell line (B-16 melanoma) in which reovirus is minimally therapeutic on its own. Specifically they demonstrate a significant improvement in Avastin/reovirus efficacy if a 24-48 hour pause is taken between the administration of Avastin and the subsequent administration of reovirus.

The improvement has to do with a disruption (increased permeability, or leakiness) of the endothelial layer of cells that form the inner layer of the blood vessels that supply the tumors, during the 24-48 hour wait before the reovirus is administered. It is during this wait, as the cells receive a pulse of VEGF165 from the tumor (that the Avastin was blocking), that the permeability increases. This is the leakiness effect that Brad has spoken about.

In the paper's figure 6D, it shows 0% survival at about 18 days after tumor seeding for reovirus therapy on its own, and for Sunitinib (Sutent; Pfizer) on its own. For Sunitinib + reovirus together, it shows a 65% survival at day 80. In figure 7A it shows 0% survival at about 18 days after tumor seeding for reovirus on its own, and at day 64 it shows 25% survival for Avastin alone, and 90% survival for avastin + reovirus. These are the 2 charts that are shown on page 7 of the March 2010 Oncolytics investor presentation at http://www.oncolyticsbiotech.com/OncolyticsBiotechInvestorPresentation_March11-2010.pdf
titled "Increasing Vascular Efflux Through Manipulation of VEGF Signaling". In these charts, "PBS" is a control … sterile phosphate-buffered saline.

This work is all based on a murine (mouse) model, so we shouldn't read too much into it directly. I do note though that all murine models that I have read of, involving the efficacy of reovirus against various cancers, have (so far) been highly predictive of what we have later seen in the equivalent human Trials.

This is the last paragraph of the Discussion section of the paper: "In summary, we have shown that manipulating VEGF165 signaling pathways within the tumor microenvironment enables systemic delivery of oncolytic virotherapy. Therapy is associated with increased vascular permeability to circulating virus, VEGF165-mediated induction of viral replication in and lysis of endothelial cells, and innate immune-mediated attack on virally infected vasculature. Importantly, because this combinatorial approach targets the tumor endothelium, these data have direct, wide-ranging, and immediate clinical applicability across a broad range of tumor types using reagents that are already approved for use in patients."

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