Oncolytics Biotech Inc. (ONCY)

[onco_investor]

Transcript of the RBC Webcast

Thanks Rjc

audio is from the link
http://www.wsw.com/webcast/rbc129/rbc129.panel1/


Safety

{18:47} As you might imagine, using a live virus on people who are dying of cancer has perceptual issues, anyway, with respect to safety. We ran overly large numbers of primate models for safety prior to going into humans, and now we have a database in the 450 patient range, with human experience. In the normal infection cycle, you might inhale or ingest 10 to 100 virions (viral particles) and we're giving 3 times 10^10 daily as an IV dosage and 10^12 particles daily as an IV dosage. It's quite a different experience from the natural infection cycle, but we're quite comfortable with what our safety profile is now. Typically on day 2 or day 3 of a 5 day cycle you get "pre-flu syndrome" as we've named it … you know; a low grade fever … a degree, a degree and a half of fever, low grade myalgia and arthralgia, and grade 1 fatigue, and a mild white blood cell depletion which is not unusually surprising given how much virus we're giving people. But that is it … and our, kind of "magic" that gets rid of symptoms is Advil or Tylenol, and it works wonderfully, so I think we're quite comfortable with that safety database now. We're pretty confident that we have the side-effect profile pinned down quite nicely now, and it's quite mild.

Host: Is there any correlation as to how sick people get and the ultimate outcome?

Brad: Actually, there's a statistical linkage between side-effects and Clinical Response, so about half the patients don't have any side-effects, and not surprisingly, those are the patients that don't have Clinical Responses, and the patients who respond are the ones that get the low grade fever and the low grade pain, and low grade fatigue; so now when the doctors see a degree or degree and a half of fever, it's a "we're going to have a Clinical Response in 2 weeks" kind of predictor, so there is a physical linkage there. That's not surprising … when you don't have a clinical response, the virus has cleared within 40 or 45 minutes on an IV administration, but when you do have a response, the virus has set up residence, as it were, in the tumor, and you're actually getting active viremia very rapidly, for weeks on end, and that's what's causing the side-effects. So there's a direct correlation between the tumor destruction, and the low grade side-effects.

Biomarkers

{29:40} The use of biomarkers has evolved in our program over time. When we first started out there really wasn't any adequate proof markers. With the Ras pathway, there's … our virus requires an activated Ras pathway and fortunately a lot of things activate the Ras pathway: mutations, overexpressions, many of the elements on the pathway actually lead to that metabolic state; but the vast majority in most indications are caused by EGFR mutation overexpression, or KRas mutation overexpression. So if you lump those two together, you actually have a pretty good subset. You can do that in two different ways. You can screen for that now, and we have approved kits in Europe for both, and an approved kit for EGFR in the States, and soon to be approved KRas kits in the US. We have a first line non-small cell lung Study running in Phase II where we're screening for KRas and EGFR status, and a second line colorectal Study where we're screening for KRas and EGFR status, as pre-screening agents.

Now the other way you can screen is by looking at the high incidences of Ras that are just naturally occurring with respect to different indications. Pancreatic for example is over 90% KRas mutant specifically. We have a randomized, and a single arm, pancreatic Study running in that. The kind of different one is metastatic disease. Metastatic disease is usually over 90% Ras activated. If you look at metastatic disease specifically, and look for clinical responses there, you get what you'd expect to get, which is very high rates of Clinical Response ... our best is out of our Head and Neck data, out of our Phase II. If you segregate and grade the clinical Responses in lung, or liver, or lymph nodes separately by RECIST, you get 80% Stable Disease or better, and 40 odd percent actual durable Partial or Complete Responses in metastatic lesions, which given the importance of metastatic disease and lifespan, it's kind of interesting. So biomarkers are really important for us, and that's the two ways we handle them … we either screen by metastatic disease (or indication), or by using a kit.

Manufacturing

{39:20} It's interesting to talk about manufacturing, because for us, manufacturing actually is the critical line to getting this product out. We're already manufacturing at commercial scale; it's a very effective manufacturing process, but we still have to go through validation and conformity runs. That's really our critical line; so we're anticipating having that all done by next year to coincide with the conclusion of enrollment in our Phase II Study with Head & Neck. What keeps us up at night isn't our clinical program, but manufacturing, and making sure that's on track. It's such a critical element. More files fail at the FDA on manufacturing issues than they do on clinical data. I think we've all seen other companies have issues with manufacturing along the line that have caused more problems; so that's what we're focusing most of our time and energy on with respect to critical line issues.

Host: And then your Phase III Trials in terms of reading out, and potential filing dates …

Brad: Well, assuming we get our enrollment done as scheduled in 2012, we should be ready to file in early 2013. Again, the clinical Trial is not as critical on the critical line as manufacturing for getting the dossier together for that particular filing date, and I think we'll make it, but it's a little mundane talking about manufacturing. It's one slide in our talk, and it's 10 years of Matt Coffee's life, distilled down to two bullet points. For us that know Matt, that's very frustrating for him, but it's like a vaccine production line now (as we found out), but it's about 4 orders of magnitude cleaner than anything that's ever been done with a vaccine line; It's been an interesting process, but that's certainly the key thing. We should be filing in a couple of years from now, or have filed already.