Canaccord Genuity webcast by Brad Thompson, CEO
Thanks to PDT on V2
Transcript Canaccord Genuity webcast by Brad Thompson, CEO of Oncolytics Biotech, on Aug 8, 2010
Good morning and thank-you for taking your time today to come and listen to Oncolytics.
Before I start I'd like to direct your attention to our forward looking statements and recent filings with the Securities and Exchange Commission and the various equivalent commissions in Canada.
Today I'd like to talk about our clinical stage product which is called Reolysin which is an unusual product, it's a live agent, it's a virus that we are looking at a number of different indications in Oncology. What I'd like to focus your primary attention on today is to talk about our phase III study which started treating patients last month in the US, UK and Belgium, which is for second line or platinum refractory head and neck patients with a very serious emphasis on squamous cell carcinomas. And we've expanded this platform into a number of other phase IIs looking at first line non-small cell lung, metastatic melanomas, and first and second line squamous cell lung non-small cell lung cancers and we're also - I'll talk briefly about another interesting indication which is pancreatic cancer in combination with Gemzar.
We have a very good I.P. portfolio and we're already manufacturing the product at commercial scale. For example, a 100 litre batch, which is the scale we are at now, a single one produces enough product for an entire clinical program and produces between 150 million and 200 million dollars worth of product, so I think we are pretty much there on manufacturing.
Reolysin contains a virus called the reovirus which is a very common environmental virus. If you were flying in during the rain last night and were walking around outside you were actually splashing it on your leg as you were walking through puddles. Anywhere between 70 and 100% of any adult mammalian population has actually been exposed to the virus by the time that they reach adulthood. But it is considered to be one of a large group of viruses that actually doesn't cause disease in humans which is the "O" in reo, which is "orphan". It's asymptomatic. Of course the way that we are delivering it is a little different than you'd get it in nature so we did have to spend a little time and energy on safety.
The only reason we are interested in it is that it has an absolute requirement to grow in cells that have the RAS growth pathway constitutively activated and it also acts primarily as a cytotoxin: it will infect a cell if the RAS pathway is activated, it will productively replicate and kill the cell in about 3 days and then progeny viruses will spread to surrounding tissue. This would be a curiosity only if this condition wasn't associated with diseases. About half of neurofibromatosis patients, for example, have a RAS pathway involvement, there's a couple of sub-cell classes of rheumatoid arthritis that have a RAS pathway involvement and the one that is of interest to us which is Oncology - about two thirds of all primary carcinomas have a RAS pathway involvement and between 90-100% of metastatic disease. And as you would expect given that differential we actually do get preferential responses in metastatic disease over primary. And of course that translates into a very, very large patient load. Every year in the Western world will come down with a new primary tumour that has a RAS pathway involved with it.
Also, our pipeline as we have it today. I'll be talking about our phase III study in head and neck in combination with carbo-tax, carboplatin paclitaxel, and briefly talking about some of our follow-up studies particularly the non-small cell lung study which is in phase II, briefly about squamous cell carcinoma for the first time which is kind of fun, pancreatic cancer and our colorectal study.
The phase III study just started enrolling last month, we actually announced opening of the study late in May and enrolled our first few patients in the first three countries early of last month and we are looking at patients with platinum refractory not platinum resistant - platinum refractory head and neck cancers. It's a two part study, it's fully blinded, the control arm is getting carbo-tax saline and the treatment arm is getting carbo-tax Reolysin, and it's interesting in that we are using adaptive statistics in the second part primarily. It was approved in the U.S. under a S.P.A. last fall, in the U.K, Belgium, and Canada subsequent to that and as you'd expect the primary endpoint is overall survival. One of the things that we discovered in our phase II study is that we do seem to get very distinct patient populations and so we are sampling very freely in this study, in order to determine markers potentially as there have been none determined as of yet, and so we are looking at EGFR, RAS, human papiloma virus status and a variety of other things to enable in the future hopefully to be able to screen in and screen out patients. There will be 80 patients in the first stage and enrolment is anticipated to be concluded in Q1 of next year, and so by ASCO next year we will have a primary read out of that first group and the second stage, which is adaptive, is most statistically likely to have 200 patients. So two years from now when I'm standing here we will actually be able to talk about final results from the entire 3A/3B structure.
The reason that we are interested in head and neck is worth talking about for a couple of minutes. Our phase I study with carbo-tax and Reo had a heavy weighting of head and neck patients in it, primarily because of the investigators practices that were on the study. We were surprised I'd have to say with the responses and lifespan - at least anecdotal lifespan - extensions that we received in the phase I study and so decided to run two phase II studies, single arm studies, with just head and neck patients with a very high concentration on squamous cell. We completed the U.K. study which had 23 patients and we are finishing off the U.S. study as we speak.
Now, what we are comparing it against is historical just to see if we have activity in the area of interest and we are primarily comparing ourselves against work that Jan Vormorken, who was the P.I. for the Erbitux registration study in Europe, in his experience and using the data from his various studies. On carbo-tax alone his estimate is, is that the response rate should be no higher than 10% for this patient group, probably less than that. Erbitux pushes that to 12 or 13% arguably, with a PFS of 2 months or less, and this is where it is very important to make sure you stick with the patient group you are looking at, 4 1/2 month median for refractory patients which is quite different than platinum failed patients. The 23 patients that we ran in our phase II study in Europe, and we reported this in June at ASCO, of the 19 evaluable we had a response rate of more than four times that, and a clinical benefit rate of just under 3 in 4 patients, and because the patients are still alive we reported the mean, but we are just under 9 months mean for survival which is just about double what we were expecting to see. From the basis of this we decided to run this phase III study. This very strong signal for this particular indication, especially platinum refractory and squamous cell populations, which tend not to respond well to conventional therapy. One of our clinical advisors said well not only is the response rate different, but the types of responses that you are seeing is quite different, and we expected this. Whether we see a response in the primary or not, almost universally we will see a response in metastatic lesions, which is highly unusual.
This is a case of lung lesions, they're on the left side top and bottom, the before and after, and post 6 cycles is around 4 1/2 to 5 months in this particular case and you are getting complete resolution of the metastatic lesions in the lungs and virtual resolution, in this case, of the primary. We also see this typical effect in nodes and liver lesions as well.
This patient was actually a nasopharyngeal, which we didn't have many of in this study. The primary actually had a fairly minor response, had a 10% regression, but the liver which is that grey mass in the upper left hand side, the descending colon on the right, had those large dark lesions scattered throughout and you are getting about a 96 or 97 volume regression in about 6 weeks and this is very typical for Reo to get these types of responses especially in metastatic lesions and in head and neck that is the primary cause of death typically is mets. So we are quite, quite pleased about this, but also quite sensitive that we have to focus on evaluating response in metastatic lesions on a differentially than primary.
Just a couple of visual ones, this particular patient actually presented with this lesion about 2/3 that size for his primary treatment of radiation, which I'm not sure what he thought that was on the side of his neck, but after he failed that and two platinum courses we put him on study and again, after about 6 weeks you're getting complete resolution of the superficial component of the tumour.
And this one I tend to show just to show the rapidity of which these tumours grow, all of these patients are rapidly growing, are rapidly progressing patients both in their primary and metastatic lesions. The pre-treatment slide in this particular case is on the day of consent, the middle slide is 18 to 19 days later when we started therapy, and again that's 6 weeks after on the right there when you've resolved all of those superficial tumours and you can see the underlying radiation damage left over from earlier therapy. So it's very, very consistent with what we see; that 40-odd percent of the patients that we get responses, respond extremely rapidly, usually you are starting to notice tumour differences within the first cycle and usually get this kind of resolution after 2 or 3 cycles. Another 30 percent or so, you are getting stable disease, they are stable disease while they are on therapy, and once they are off therapy their tumours will start to grow again, either very quickly or some months later, and then 25 percent or so of the patients grow right through the therapy altogether and hopefully we can find out what that is.
One of our clinical advisors noted to us in the middle of our phase II study, that squamous cell, these kind of responses in squamous cell are quite unusual, but there are other indications that are squamous cell based, of course, and they are essentially the same disease just in a different location. And so the first one that we thought of looking at was squamous cell lung and just for fun, to show one's studies very early on, this particular patient has - this is the first patient on our phase II in the States in squamous cell, the green arrow, the top green arrow on the left is the primary which is a double fist size, on end, tumour in the right upper lung and you can see as it progresses post cycle 2 - it's very quickly, that's only about 4 weeks out - you are getting about a 70% volumetric regression and it continues to shrink after 4 cycles and that's where this patient is now, and you're also seeing plural mets similarly responding. If we can maintain these kinds of responses in this particular study I think it would be very encouraging. There's been some unfortunate failures in squamous cell lung recently and this is highly encouraging, though obviously just a single patient. We have another 5 or 6 patients that will be reading out in the very near future.
Obviously going ahead and screening is what people are doing in Oncology today, and we are as well. If you look at tumours with a RAS pathway activation, they have a number of subsets in them that are already commercially important. EGFR activation or mutation signals through RAS so those are a subset of the whole RAS pathway activation universe, and of course they have signification sales with a number of products in that particular area. Two years ago at ASCO people noted that non-small cell lung and colorectal patients that have KRAS as well as EGFR mutations, that the EGFR based drugs weren't working particularly well. Its a little fuzzier with non-small cell lung than it is with colorectal, but that provided an opening to us to pre-screen patient populations with those two mutations, and I'll be talking about that briefly. But you also start thinking about screening by indication where you have almost universal RAS activation and there are a couple of cases where that's particularly the case and so you can pre-screen by disease as well as by actually doing the screening.
First, with non-small cell lung, in our study we are screening for KRAS and EGFR status and between 15-20% of non-small cell lungs are KRAS mutated and that's the patient population that we are after. So if a patient comes into this study they get screened for EGFR and KRAS, if they are KRAS negative they go onto standard of care which is carbo-tax and one of the EGFR drugs. If they have the KRAS mutation they are excluded from that and are treated on our study. We are a significant way through the enrolment on this study and I would expect we would be announcing top-line data hopefully later this year.
<??? 14:33> with colorectal cancer, we had clinical data on carbo-tax combinations so we could go straight into phase II, but we needed to go back into the lab because of the Irinotecan component of FOLFIRI, and we're just about to start enrolment in a phase I study with REO combined with FOLFIRI - again, same thing, while patients fail first line in this case are screened for EGFR status and KRAS, if they have the KRAS mutation they'll go onto our study. In this case its a much bigger percentage however, it's almost half of the patients in 2nd line colorectal are now being excluded from EGFR status because they have KRAS mutations so this is a significant patient group for us.
And lastly, the one that I find kind of interesting is one that we've been working on for quite some time, is that pancreatic cancer is essentially 100% RAS activated, about 95% KRAS mutant and the rest are RAS activated for a variety of other reasons, so the indication is pre-screened for RAS activation, and certainly in the lab, REO's cured in combination with Gemzar in animal models for panc. This, again, is a very early patient out of this particular study, but you'll notice this is post-cycle 1. So this patient's scans were a few weeks apart from the start to the after, and there is two things here - the primary which is the bottom lower left and right and the pancreatic head has a partial response already, and the top which is a metastatic lesion of hepatic hilar lymph node is also a strong partial response. Very aggressive responses, very atypical for Gemzar all by itself in this particular case. And so, again, we are hoping that a few patients further on will have something a little more interesting to show you, but it is certainly encouraging very early on to see these kind of very aggressive results, again, very quickly, which is very typical of REO combinations if you are going to get a response.
From the perspective of safety I think we've gone above and beyond because this is a live agent. We've now treated over 330 patients of our own and the NCI has treated another probably 40 or 50 by now. Most of these patients have been treated at intravenous dosages at our standard I.V. dosage which is three times ten to the tenth. We still don't have an M.T.D. and the tox is completely consistent. Usually on day 3 of a 5 day cycle, you'll get a mild fever, a mild arthralgia, and grade 1 or grade 2 fatigue. Blood chemistry is usually low grade lymphopenia and nutropenia and about 6% of the patients get transient lymphopenia and nutropenia and it's very atypical in that it presents and resolves on the same day which is not classic lymphopenia by any standard. And it's very, very consistent and it doesn't exacerbate or stack, usually, with other drug's toxicities. The exception being that if you have grade 3 or grade 4 nutropenia/lymphopenia induced by Gemzar, I would be cautious at using this in combination with high dose REO, I think that's not prudent - would be a nice way of saying it.
We've got over 200 patents issued worldwide including 36 U.S., 34 of which are specific to REO and a couple that are with other viruses, and they cover everything from composition of matter, to pharmaceutical use and manufacturing and so on. We've done an incredible job of putting together an I.P. base that hopefully will withstand challenge at some future date.
And as I mentioned, manufacturing has resolved itself quite nicely, we are using the final formulation for commercial use now in our phase III study and certainly our cost of goods is expected to be very, very , very low for a biologic given this current process.
We trade both on NASDAQ and on Toronto, Cannacord is actually the lead agent, listing us on both, and we've had a long association with Cannacord. We have cash to take us to next fall, which is 4 or 5 months after the read out of our primary data on our phase IIIA and finish up all of our phase II studies.
Just quickly in summation: our candidate's in the clinic is called Reolysin is in a phase III study that will have primary data a year from now and final data two years from now and we have a number of other phase II studies that will read out - mostly between now and next year just prior to our phase IIIA data, and I'd like to thank you for your time and attention today.
