ONCY - Oncolytics Biotech, Inc. - 2013 Stifel Nicolaus Weisel Healthcare Conference Transcript Ticker:ONCYCompany Name:Oncolytics Biotech, Inc.Event Title:2013 Stifel Nicolaus Weisel Healthcare Conference TranscriptEvent Date:11-Sep-2013Event Time:01:30 PM ETPresentation Brian Klein Analyst, Stifel Nicolaus My name is Brian Klein. I am one of the biotech analyst here at Stifel. It is my great pleasure to introduce our next presenting company Oncolytics Biotech based out of Canada. And speaking for them today will be Brad Thompson their CEO. Thank you Brad. Brad Thompson, PhD Chairman, President and Chief Executive Officer Thanks, Brian. Before I begin, I'd like to draw your attention to our forward-looking statements and recent filings with the Securities and Exchange Commission. And I believe 13 commissions in Canada. Today I'll be talking exclusively about our -- in Phase III development which is real licensed. And just to draw people's attention to the fact that behind our Phase III study in head and neck cancer is it actually fixed Phase II randomized studies and other indications. including both adeno and squamous cell lung and non-small cell lung cancer, colorectal, breast, pancreas, prostate and ovarian. And we have a very robust intellectual property portfolio which we will now dwell upon. And we are already manufacturing at the lower end of commercial scale with the product in the United States. The product is a little unusual and it contains a live agent. It contains the virus called the reo-virus. Reo stands for respiratory enteric orphan virus. The orphan designation is important. And given the viruses that are not known to cause diseases in humans and this is clearly one of those. About half of children by age five that are serial converted against the virus and virtually all adults. And so it's a very common environment virus, which is actually quite common with the virus that actually don't cause the disease causing virus that tend to be rare on population evident. We've administered the product to the vast majority of patients intravenously, but we have also done -- work and direct injection into the brain intratecally, which is the most aggressive safety way of doing it from a safety challenge perspective. Intracellular anyway we actually understand the mechanism of actions very well. This particular virus will only replicate inside a cell that has an activated RAS pathway which is digitally activated. And that can occur through mutations or over expressions of any element on the pathway. So EGFR is on that pathway, KRAF, a number of other elements signal through that pathway. So any mutations or over expressions of any of those elements results in -- activation. When that pathway is activated, it actually deactivates any double stranded RNA viral defense mechanism that all cell path is modulated by a compound called protien kinase R. And that leaves the cell open to infection and in this case a productive infection by a double stranded RNA virus. The virus enters the cell like that. It will infect it.. Three days later the cell will die and you -- 40,000 to 50,000 virus into the environment. It is a self replicating drug. It is intracellular. Extra cellularly this story is a little more complicated. There is a secondary immune response against cold viral tumor antigen. That only happens after the virus could actually kill the tumor cells. And that will in long-term survival and response is only being elucidated now. So that is the remaining part of this particular story. Just on a -- perspective, it is important to note that the differentiation does occur within the cell not extracellularly or at a receptor level. The virus is fairly -- entering into cells and it will actually enter into every cell in your body. It is the inside cytoplasmic recognition of RAS activation that actually determines whether the virus will replicate or not. And so there is no differentiation based on the -- Now that's important when you look at specificity. And we conducted two small single arm studies actually looking at specificity and looking at whether you saw by standard effects with normal tissues surrounding metastatic legions in both cases. And the first study was a T2 prostate study which we've reported on before and the second study more recently was in the metastatic colorectal population where we were looking at the metastatis to deliver and in our cases the patients were treated with REO and with monotherapy intravenously and then delivering metastases to excise surgically and it is absolutely selective in both studies clear evidence that is normal in this case a parasite -- that in dying tumor and so this will contact and actually not getting by standard with our actually never seen anything as selective before, we are actually did show once in one cell that we infected in parasite which is actually on this wide for disclosure next to red arrow, but in the other 100 we have got, we've actually never seen anything so I think quite reassuring that the safety profile that we would see which is very benign is actually matched at the cellular level. I won't dwell on the potential market for Raf active agent but two-thirds of all solid tumors have Raf involvement sort of 90 plus percent of metastatic disease invariable percentages of non-solid tumors. I most lymphomas are in the higher 60% and 70%, but there are a number of lymphomas that have a much lower percent of RAS involvement who reasonably don't understand. And of course that's generates a very large patient population in the Western world that has RAS involved with new patients of at least 5 million a year. And about half of those will die by a metastatic disease which has even a higher percentage of RAS pathway. We've in our studies that we have sponsored ourselves, we have enrolled over 600 patients now. As you include the patients that have been enrolled in other peoples sponsored studies in the NCI here in the United States., the NCI in Canada and various groups in the United Kingdom. We are just under a thousand patients who are treated to date. And that's just under 30 and they are just going to be 30 in the next day or so. studies mostly single arm studies and mostly studies are being addressed looking at different indications and different drug combination and mostly as a learning exercise.
ONCY - Oncolytics Biotech, Inc. - 2013 Stifel Nicolaus Weisel Healthcare Conference Transcript Animal models aren't particularly predictive on combination therapy effects, or on the effects of a large macro molecules from what we think in that way virus, interactions with need of tumors and so we have embarked along upon a very large number of learning studies if you want to think about that way which have now led to our randomized program. This is our randomized program. Today we have currently enrolling in seven -- enrolled or patient enrollment in seven studies, I will be talking about our Head and Neck study in a moment. But behind that is the six other studies as I described the most further enrollment are the ovarian study and pancreatic studies which we are doing in our -- in United States and in behind that enrollment are the four Covidien studies. And so I would expect over the next 15 months, these other six days two studies will have top line data coming out of them. It is going to be a very mixed five quarters for us with respect to our first redose on our randomized studies. Now, I want to talk today specifically about three studies, two of them are single arm studies and the third being our Phase 3 study. The first part of our Phase 3 study had MEK cancer. I wanted to just address an adenocarcinoma of the lung program. This is actually our first study were we actually did genotyping on patients as an entrance criteria. And in this particular patient population we were looking at patients that were KRAF mutant or EGFR mutations over expression. So 100% of these patients have one or both of these markers. And we assume that since these are both activating mutations for the Raf pathway that should be fairly predictive of response and if you look at the patients 90% are more stable disease better both in time and magnitude response by resist. So fairly predictive there is texture to this which will be presented later this year. There is actually a different pattern between key Raf only patients UGFR patients and of course our UGFR mutations over special they are not equal as we now know these days and patients who have both and that will be presented later this year at our conference. It's interesting however that you can actually get this kind of predictive from fairly predictive outcomes from fairly two routine tests that are done on these patients these days currently. This is a representative to our response. You see we have done an interesting case in that if you included with a drug combination you would typically get. When you do see response they are faster than the drug combo itself. You see our corporate tax response and you add REO to it, it might not change the response, but you'll certainly see it sooner. And we do often I think change the responses. This is the case of very rapid responses about after three weeks of initiation of very bulky tumors that have gone through the abdominal walls and actually was expressed through the surface going on that the top left and right panel and the metastatic region in the lower left and right panel. And there is a very typical response on REOLYSIN. The other response that you see is quite late. It is often months after you stopped therapy with the immune response. So you see very early responses or very late responses and it is sometimes the combination of both with not much in between which is very unusual. I have to say it the very unusual pattern for response. The other single arm study and this particular study we are treating up again call it half tax and realizing the combination and really looking at the early shrinkage on patients measured in a percent case basis. The interesting thing as we had 92% of the patients actually limited shrinkage so zero percent are better -- are actually better than zero percent so not to resist 20% growth are better but actual shrinkage which loans itself very strong thinking about this as we're starting at least. We're currently doing patient surveys looking at the stage one, stage two patients which are clearly in the -- population and stage three patients which are active therapeutic population. And I think those surveys will actually determine which follow up study will be of our particular study as the randomized study. Pointed out the Coincidentally the percent is only coincidental. The percentage of patients who had shrinkage also were matched. We can do better by resist criteria, but that is an coincident. I think our waterfall graph actually represents the kind of interesting part about shrinkage more aptly. Most of the patients are shrinking certainly 35% to 40% more in the linear dimension. If it wasn't at 60% to 70% of most of volumetric regression, which certainly is a great deal of interest to surgeons. That certainly makes that excision a lot easier. And this is both metastatic and the primary lesion Actually in this study the primary lesion actually shrunk a tiny bit more than the metastatic legion overall on a percent shrinkage basis. And both categories of lesions were getting this type of shrinkage in a very difficult to treat patient population. -- scan to actually show this. I am giving actually a very short patient cycle. This is actually the seventh best shrinkage, not the best shrinkage that came out of this study. There is a large bulky disease in the upper half again post cycle three and half to four weeks out in this case. And you are getting very rapid regression. Interesting enough we are not actually seeing the weeping or the bleeding associated with the VegF family treatment in squamous cell patient populations despite the that you seeing rather aggressive reduction in tumor both very rapidly, which we are watching very carefully and we can see a single incidence to that.Our Phase III program on head and neck cancer. We will be reporting in the near future. The study was designed as a two stage study. The first stage was designed more as a ranging study defined as a patient population and to also because we actually have very little knowledge about how to control on suppose to do in the study to actually help enable us to power the second stage properly, so, finding the right patient population and also quantifying the control arm. Now, the reason for that is a bit historical these are second line patients that are taxing naive patent refractory patients. But the second line approved therapy of course is very good drug Erbitux but it's not using the second line, so it's really not the commonly used with the approved therapy, the most common though not approved therapy is Erbitux and so there is really not a really good understanding about how that patient population will respond with the effective standard of care. And so this initial per stage of the study with we've designed to answer those two questions, patients were enrolled in 14 countries, 10 in United States and 12 countries in Europe. And we've finished the 157 first stage enrollment in late Q3 of 2012. –
The primary end points of overall survival, the secondary end point progression-free survival and a number of tumor specific velocity and the magnitude of response measures in the tumors in both the primary and in metastatic disease and it has a fairly complicated end point set. And we expect as soon as we cross the number of events being our overall survival to be breaking the blind and then doing an analysis there, immediately thereafter. We did a limited un-blinding on one specific element of the data in Q4 of last year. And what we were looking at is really a velocity of response. So it is very much like that squamous cell graph that I showed just a couple of minutes ago where we were looking at pre-treatment and six week which is the first scan shrinkage and so it's really a velocity measure and looking at the original -- tumors separately, we got a numeric from numeric trend that was not statistical in original but we did actually get a specifically significant difference in the rate of shrinkage because of that way on the metastatic tumor side and again which would indicate that this could usually be a used as enlargement in the patient cases where that could be used but also there has been a number of cases next of our in particular for our only velocity of tumor response is translated into clinical benefit despite not getting magnitude of response measures later. And so we will see if that includes the case of this particular study in the very near future. An unusual treatment is to look at as move waterfall graph of the percent shrinkage of the control metastatic lesions versus metastatic lesions on a patient-by-patient basis. And what this translates into is it is roughly between the 10% and 15% long term increase in shrinkage in -- patients included over the six-week period. So if you minus on tax on --, you can expect to be minus 40 to 45 on the --, or if you are plus 40 on -- tax you could expect to be plus 25 or plus 30 unrealized. It is designed to cross the entire patient population is pretty much the same at each extreme which is interesting both at the worse case and best case scenarios as you get an enhanced effect with the REO. But again I think this points towards the fact that the REO- - utility in new adjuvant. And we'll see if it has utility as an active therapeutic. And what is interesting in this particular case is to see that touch in early period of time. As I mentioned earlier between us and our collaborators we are now just under a 1000 patients who enrolled and 620 -- below 620 those who have been for our direct sponsored study, most of which are being intravenous of all the collaborator patients have been intravenous as well. And we still don't have a mark in -- dose, as a modern therapy basically it has been growing from the clinical perspective so low grade fewer muscle joint pain and fatigue usually resolved on the same day or that it presents and if you look at the quite often at Grade I, Grade II at the same time that you get the clinical symptomology, it's an unusual neutropenia and it's very much like the vaccine type effect that you typically see, which is thought to be sales extra trading in the tissue and then are reinfiltrating infiltrating back into the blood stream and that's why the numbers drop. And it is very common with viral based vaccine and we're actually just starting to get some pathological estimates if this is indeed the case. So it is not a true lymphopenia. If however you stack it with a -- like high dose Gemzar, like the European dosages of Gemzar you can actually push yourselves into -- great toxicities in the lymphopenia of grade 3 and grade 4. And that's the caution that we have to date with respect to safety as to watch REO use when you are stacking. or within the agent that has that common symptom already. And we have very broad intellectual property base including over 50 U.S. issued patents. A composition of matter claims -- our goal is 2028, our pharmaceutical used patents through 2023 and manufacturing and combination are mostly in between those two days, but I think the important thing is that you need to file rather aggressively. And of course with the intend of having long patent run way if you want to think of it that way both product approval. Manufacturing it gets a little uncomfortable when I saw slide one has two bullet points which represents 12 years of their life, but I think that is just success, and we actually have our commercial formulation of the virus already available to us for the final course and the commercial manufacturing with our colleagues with AFC corresponding California and we spend a lot of time and energy making sure that we have a commercially viable process both from the cost and profitability perspective and we believe we've achieved that. We trade both on Toronto and on NASDAQ and the majority of our shares now trade on NASDAQ that's part of 70% of our volume is now on NASDAQ. And we just didn't provide the number we had cash in Q1 2015 with our anticipated program. So just quickly in summary. We have again just a product that I like to reemphasize based on the live agent, the virus, the REO virus what is called the REOLYSIN. We have seven randomized studies currently either completing enrollment or ongoing enrollment that will report out in the next five quarters. And hopefully we are backed off with an IP base and the manufacturing -- that will stand the test of time. Thank you very much for your time and attention. Are we doing questions Brian or not? We have a few minutes. We are now doing the fireside chat format. It is a pseudo fireside chatting, so anybody having a question or two. Q & A Brian Klein Analyst, Stifel Nicolaus You guys were previously conducting a study of REOLYSIN realized in the combination with Cyclophosphamide any update on that trial? Brad Thompson, PhD Chairman, President and Chief Executive Officer The purpose of our, it was a single arm study with Cyclophosphamide is a combination and the purpose was to see what dosage of cyclophosphamide would we actually suppress the immune response to reovirus, which I know is kind of backwards but the -- and we're surprised to find out that you actually never do even at clinical dosage of Cyclophosphamide you still get a rather robust response immune response with reovirus. Now the reason we are interested now is that with the -- in the early days of viral therapies that the immune system would block viral delivery from injection side to tumor which is part of reason to believe that mostly inject a virus directly generally in the tumors and we just recently find that the immure system doesn't block reovirus at all, virus takes on everything but red blood cells basically and it is invisible to the immune system. So that study is purposed more or less secured with the effective time. Now Cyclophosphamide is virtually a drug that is still very commonly used in children. And we just recently concluded a monotherapy study in children with the COG in the U.S. And one of the drugs we're anticipating looking at in combination with Cyclo. And the reason that we're doing that is because we have the data from the other studies. So it's an interesting concept that didn't materialize. –
Analyz Thiz AMRI Albany Molecular Research, Inc.AMT American Tower CorpJAH Jarden Corporation More... ONCY - Oncolytics Biotech, Inc. - 2013 Stifel Nicolaus Weisel Healthcare Conference Transcript I am still surprised that we didn't see new suppression against this virus. We just don't see it. Oncologists that we talk to say that's quite common that they still feel a lot of bacterial infections, but they hardly see viral infections. So chemo tends to be beat up the immune system selectively that overtime. And is there overall eventually realizing the maintenance therapy is beyond combination with chemo? Brad Thompson, PhD Chairman, President and Chief Executive Officer I am not sure if you're on the webcast of the question with do we state the diminution speaker is but do we state the diminution speaker is but I mean do we see diminution overtime of effect and we don't, I mean that maybe the case but we haven't yet seen diminution of effect overtime with many cycles of reovirus and in some cases quite the opposite, for example we did a monotherapy on metastatics a common study a number of years ago, and we have patients out over three years in a number of cases with monthly reovirus and they all thought they were disease free all went off of reovirus and immediately progressed --. So you are seeing continued effect and that's real with monotherapy so I would argue that maintenance is at least quite possible. A little tragically. It is actually three patients who had that case. -- years of glaucoma that is unusual especially when you have one -- which they all did and they all died within six weeks or eight weeks. It is kind of tragic, but it did prove that the maintenance therapy was a option. Brian Klein Analyst, Stifel Nicolaus Okay. Thanks so much Brad. Brad Thompson, PhD Chairman, President and Chief Executive Officer Thank you. -
I suggest LISTENING TO A REPLAY of this Stifel Nicolaus conference in Boston. The transcript is far from perfect; it was probably done by computer and not checked by a knowledgeable person before publication.
In the first Q&A response Brad described Reolysin "hitchhiking" on blood cells, but the transcript missed this point completely.
In the second Q&A about long-term therapy and patients who thought they were "cured" after 3 years on Reolysin and then decided to stop taking it and unfortunately progressed (died) shortly thereafter. The transcript quotes Brad describing "years of glaucoma that is unusual" which he clearly did not say.
Listen for yourself.
Sentiment: Strong Buy
I listened to it and found it to be pretty depressing. Not what I wanted to hear in content or tenor. Brad sounded like he was really bored and didn't want to be there. Additionally, several times he stated or implied something like, "we always have neoadjuvant use to fall back on". Not a ringing endorsement from a person that ought to have an inkling of how the trials are going. Give it a listen. You decide.