The Oncolytic Times: Oncolytics Biotech News and Information: November 2007

11/27/2007 7:08:59 AM ET

CALGARY, AB --- November 27, 2007 - Oncolytics Biotech Inc. (TSX: ONC, NASDAQ: ONCY) (“Oncolytics”) today announced that it has been granted U.S. Patent 7,300,650 entitled “Reovirus for the Treatment of Neoplasia.” The claims describe methods of using the reovirus to treat cancers that have inactivated PKR, whether the PKR is inactivated by mutation of Ras or by other factors. PKR is a host cellular protein responsible for preventing virus replication within a cell. Tumour cells lacking the activity of PKR are susceptible to reovirus replication and subsequently, cancer cell killing.

“This patent represents a significant expansion of our intellectual property portfolio,” said Dr. Matt Coffey, Chief Scientific Officer of Oncolytics. “The claims cover additional pathways whereby tumours can become susceptible to reovirus infection and cell death.”

About Oncolytics Biotech Inc.Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics’ clinical program includes a variety of Phase I and Phase II human trials using REOLYSIN®, its proprietary formulation of the human reovirus, alone and in combination with radiation or chemotherapy. For further information about Oncolytics, please visit http://www.oncolyticsbiotech.com/

This news release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including among others, the Company’s belief as to the importance of the issuance of this patent, the safety and efficacy of the reovirus, the Company’s expectations as to the potential applications of the patented technology and other statements relating to anticipated developments in the Company’s business and technologies, involve known and unknown risks and uncertainties that could cause the Company’s actual results to differ materially from those in the forward looking statements. Such risks and uncertainties include, among others, the efficacy of REOLYSIN® as a cancer treatment, the success and timely completion of clinical studies and trials, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements.

The following is posted for informational purposes only and so that the text can be searched and referenced. Although I have made every effort to ensure accuracy, no warranties are made or implied. I encourage everyone to listen to the original source.

0:00
Speaking on behalf of Oncolytics, Brad Thompson, CEO and President.

Thanks very much.

We trade both on NASDAQ and on Toronto, so if I can draw your attention to the recent filings with the securities and exchange commission and all thirteen security commissions in Canada and recent statements that we've made.

Oncolytics biotech is a relatively early-stage cancer company looking at using viruses for the treatment of cancers, and we're amongst a group of probably nine or ten biotech companies (half are public, half are not) that are looking at a variety of different viruses either engineered or not. For treating a variety of different cancers and I think that one of the interesting features of this entire group, that as a group, we've probably treated somewhere between four and five-thousand patients, if you include some of the gene therapy studies.

And it's probably the safest, honestly, new biologic group that’s come through regardless of which ever virus there is.

I’ll talk about our clinical program today. Just reassure everybody, everything that I'm talking about today we already have funding for.

And I’ll be just talking about our product that’s actually in the clinic which is called Reolysin.

Reolysin is a kind of interesting product it contains an unmodified virus. Sort of a subset in the viral area. Looking at the viruses that haven't actually been genetically engineered or changed.

And it's a fully replication competent virus, so for when it infects a cell it actually produces anywhere between two and twenty or twenty-five thousand progeny virus. So it's a self magnifying, self amplifying drug, which makes toxicology studies somewhat interesting.

In the native form it’s asymptomatic. If you're walking through Central Park today and splash through a puddle today you would be breathing in reovirus, anywhere between ten and a hundred virion particles.

And of course you're doing it little differently, our IV doses are 30 billion active particles per day for five days. And it’s interesting that it doesn't actually cause any disease, it's completely asymptomatic in its natural form. Why it's interesting to us as a potential therapeutic is that it has an absolute selectivity for growing in ras activated cells of all kinds.

Of course ras activation is particular interesting. In oncology anywhere between seventy-five and a hundred percent of the more aggressive cancers are ras activated. And between 65% and 75% of all the mainstream carcinomas are ras activated. So it's a good target.

And what that translates into if you look at people around the world that can actually afford health care there is about 5 million new patients a year that have a ras active tumor or condition evolve.

02:53

This virus is fairly promiscuous. It actually goes into every cell in your body. And if the cell is not ras activated, so your normal cells and say a third or so or little less than a third of cancer cell that don’t have ras, a compound called PKR is active and it blocks translation, so there's no viral protein made and replication is actually halted.

03:17

It’s a little more complicated than that of course. For those of you that know about ras, I apologize for condensing a very complicated pathway into one angry red dot. But in a ras activated cell, the thing that’s important to Reolysin is that it actually deactivates PKR, which is permissive to translation and allows the virus that last step into replication.

Once a virus comes into contact with a cell like this it kills it usually in about three days. And like I said you get a very large number of viral progeny.

It's never that simple, in humans we’ve found that it's actually two modes of action, in humans there's two types of tumor responses. Sometimes they're mixed which also complicates things.

The first is what I just described. The virus infects cells, kill cells, spreads around the tumor till it can't find a more cells and you get a very very rapid and robust tumor response.

What we found is that in the act of killing the cells, and the virus has actually kill the cells for this to happen, you revisualize the tumor to the immune system and you get a very robust and long-duration secondary immune response, which results in a slow but very long-duration tumors shrinkage over time, and sometimes we see tumor shrinking six, nine, twelve months…long, long beyond the time period we've actually ceased treatment.

04:39

This came out of my virology lab, not a cancer lab, and we were first to file in the area and our patent portfolio is developing rather robustly now. We only report on US and our home jurisdiction, which is Canada. But we have over 150 patents issued worldwide now and over 180 pending applications. And they cover pretty much everything all the way through manufacturing through composition of matter, through pharmaceutical use, and combination therapy which is very important for us as a commercial target.

You will very rarely hear somebody talk about manufacturing and biologics and that's for two reasons. One it’s not a problem, which is rare, or it’s a very large problem, which is unfortunately much more common. We spend a lot of time and energy working towards commercial scale and commercial cost effective process for this particular product. It is not easy, growing virus at scale and purifying them and making them stable as many people in the field have found out to their problems.

But currently we're just finishing off our low-end commercial scale development, which is 100 L, which produces between 40 and 50,000 dosages per batch, which gives you a million-ish dosages a year out of a small 100 L facility which is certainly enough for commercial introduction.

And we will be doing most multiple replication runs next year to support our regulatory filing.

06:04
With respect safety, I mean, this is a live active agent and we’re giving tons of it to you for many days in a row, not inhaling ten particles of it in Central Park,

We've treated just under150 patients now, most of which are intravenous, up to 30 billion active particles a day. There is actually twenty times that many total particles, so this is a very large protein load and it also got an infectious agent in it. And we have yet to reach maximum tolerated dose and the toxicities has been between, what I consider, a mild protein tox and a very mild viral tox. Generally very mild. The most common side effect are a degree, degree and a half fever, mild myalgia, arthralgia, and sort of pre-flu like symptoms that last usually for a day or so.

06:53
On the blood chemistry you're looking at low-grade lymphopenia/neutropenia which wouldn't be surprised to anybody who's ever worked in virology. And we've had a very small number of patients transiently go into grade three lymphopenia/neutropenia, and that disappears usually in a few hours which I have absolutely no explanation for. I've never seen lymphopenia/neutropenia last that short of a period of time, honestly. So we don't have an explanation for that. Interestingly enough, they’re usually day two, and they usually starts in the morning, day two, and they’re usually done by lunch. So it's a very predictable, which is what you like to have

07:23

This is our clinical program for REOLYSIN. It's a very broad program for a single agent I have to say, and there's a reason for that. We’re looking at both intratumoural administration versus systemic, and co-therapy versus monotherapy. And recently we've announced an interesting immunomodulation study we’re actually immunomodulating a patient’s immune system and then infecting them with the virus, which is kind of a little edgy. I think the reason for this is that the product seems, at least in the lab, to be extremely active and what we wanted to do is coincide our phase II data all coming available for his programs next year in order to have us take the II studies with the highest degree of signal into pivotal studies starting next year. This really gives us an opportunity to make sure that we understand the product in early-stage clinical development.

This briefly, we’re doing a monotherapy glio program in the states. Honestly most other big pharma colleagues don't care about glioma, it’s to small an indication. It's also very intransigent to therapy. But it’s certainly a very good target for, not just this virus, but a number of the viral agents. They all seem to have activity in glio.

We are just finishing off a phase I study here in the US, a previous phase I study we did in Canada had some interesting results with respect to lifespan. Multiple recurrent gliomas were enrolled with sort of three to six-month life expectancies, so one would expect that if the patients lived year or longer it would be of interest, and a quarter of the patients did that. We have one patient right now that's quote cured, I mean he’s fine.

09:00
Small data set, but certainly was encourage enough for us to repeat it, in essence, in the United States, and we will be in phase II study Q1 next year.

We are combining REOLYSIN with radiotherapy. This agent is probably more synergistic with radiation than any other agent that I’ve seen before, but it's on a selective basis. Normally, radiation sensitizers sensitize the entire body. It's a very known common phenomenon in radiation therapy, REOLYSIN does not. What we found in our phase Ia/Ib program is that you get the viral side effects, you get the radiation side effects, but you don't get both or any additive between the two, which is good. We’re one patient away from finishing the Ib and have been for a while. It's a very awkward protocol.

But we've brought in a phase II at the low dose, which is 20Gy (European measurement), in the UK, and we should be finishing enrollment in this study Q2 next year. It's primarily head, neck and esophageal cancers with a subset of melanomas. We’re starting to see some interesting things in that area and were measuring both local and remote responses, which is interesting for a local therapy.

10:08

The reason for that is the following: and we’ve kindly highlighted the tumors in this scan green… this is a patient who had failed multiple chemo and radiation cycles with head/neck tumors and subclavical lymph nodes…Monday through Friday radiation, Tuesday to Thursday reovirus. And two months out we had a strong partial response, at six months, the tumors still shrinking which is kind of interesting since the virus's been gone for 5 1/2 months by that point in time.

The really interesting thing with this patient is the remote response. A medial spinal tumor is sitting on top of the heart complex between two lung cavities there. And so you're treating in the throat and you’re getting response around the heart. So it's a strong partial response outside the radiation field. And that was the durable response. Both of these were partial responses by resist criteria. So we were really quite pleased with that. So we're looking at local and remote responses in our UK phase II.

Obviously, treating people systemically is the way to go in oncology. This virus does not go across the gut barrier, so we treat intravenously, which fortunately in oncology is perfectly acceptable, it gives you the largest patient population.

In two phase I studies we've completed its very well tolerated at very high dosages. In both studies, and these were end stage patients that have failed all other therapy, we had a variety of tumor regression, but posts interestingly in a very large variety of different indications.

11:44
The UK study was a larger study in little bit more complicated. It was a dose and frequent escalation and we ended up at five Monday through Friday dosing and went up to our highest IV dose (3x10¹⁰TCID₅₀).

And it showed a very important technical features, this is a particle, and it was an open question whether that particle will make it into tumors. It does, and in a variety different places of the body. There were seven patients in the study that showed tumor responses in six different cancers in different places in different places in the body.

So that answered that question, and the holy grail in the viral area, which was actually isolating non-input virus out of tumors that had shrank, which we showed quite clearly.

The phase I in the US, was a single administration, we needed to make sure that five wasn't better than one, from a frequency perspective. And I was a little surprised to see that that actually doesn't matter whether one or five, and this is again in end-stage patients who had failed all their therapy…by resist criteria eighteen had stable disease and better including a partial response … again the toxicities were mild.

So this gives us some flexibility on dosing, we can do either one day or five day. And there are very good reason in combination studies to be looking at different dosing.

This is one of our patients from our UK study, metastatic prostate cancer. Actually this is a patient post-prostatectomy who had gone from a PSA of 20 to 100 in a couple months before coming into study so very active metastatic lesions in the lymph nodes and on the other side of the bladder.

13:31
This is actually two cycles into the treatment. The Patient was treated IV Monday, Friday, three weeks off, Monday thru Friday. And then the second scan you’ll see the large tumor on the left hand side of the bladder is actually getting dark, which is indication that the tumors is dying and the patient's PSA fell from 100 to 40 in those three weeks too. So we’re actually getting good tumor killing in this particular case.

Just for the techno-nerds amongst us, this is a micrograph of a biopsy of a tumor, which was completely dead on the inside by the way, it's completely scattered virus and we were actually able to isolate….the actually number is actually low, we’ve reconfirmed that. You're actually looking at between ten and a hundred million viral particles per gram of tissue, which is pretty remarkable, I mean the tumor is turning into a drug factory inside the human body.

From there we have moved in to, I think, a fairly broad phase two program, coincidently all the monotherapy studies in this poster piece in the UK. That was not by design. We're running a phase II sarcoma, a variety of different sarcomas with the commonality being pulmonary involvement in all cases. There is no good standard of care here and we're well into enrollment on that, and the prime sight there is San Antonio.

Once we finish that study we will probably be doing a three arm study looking at reovirus versus docetaxel plus or minus reovirus on the other arms. So those will be the other arms. And that will be a pivotal study.

15:00
The NCI is running two phase II’s for us, one in melanoma on monotherapy and an interesting one in ovarian cancer where we’re treating intraperitoneally and intravenously simultaneously. And that’s mostly to get basal response rates in those patient populations.

We just recently announced a co-therapy study with cyclophosphamide, which is a very old line chemotherapeutic. Low dosages, it’s immunomodulatory, it dampens a variety of elements of the immune system. And in animals we found that if you take the edge off the immune system reovirus goes from being quite a good therapy to being curative in most cases. So we felt compelled to investigate this. This is really one of those things that you really need to take a look at. We just recently approved in the first part of study, which is using actually the therapeutic dose of Reolysin throughout, the 3x10¹⁰dosage, is to find the actual low-dose cyclophosphamide that gives us the immunomodulatory that we require to actually start getting the more robust tumor responses. It’s a very very edgy study. But if it works out the way it does in animals, I think it's going to fundamentally change how we view viral therapy. And we are all quite excited and just a tad nervous about it, I have to admit to.

Our mainstream combination studies are all underway. We’re just finishing off the dose escalation components, and I'll go straight into phase II, and we're combining Reolysin with chemotherapeutics like docetaxel, carboplatinum, and the gemzar study. And those are all going on in the UK at this time. Once we are finished we’ll go into phase II’s in the UK and the plan is to get at least two of those studies into parallel phase II's in the United States at the same time.

The reason we’re interested co-therapy is that Reolysin is strongly synergistic with virtually everything. And I mean very strongly synergistic, it’s just not radiation, it’s virtually every chemotherapeutic. We’re just going through the new line biologics right now and we’re seeing a similar trend. Most of this work was done at the National Cancers Institute, but we’ve confirmed it at a number of other places. Just to make sure we trust the synergy data.

But honestly, again, when you look at the coefficients, I’ve never seen anything this synergistic in the lab. It’s really quite remarkable that you get this level of synergy with a live biologic.

17:16
This is the sort of thing that you see, it doesn't really matter what agent it is, this is Gemzar, in this particular case. This is work done out of Cornell, presented earlier this year at ACR. Kind of a typical experiment. ….in this case…it’s a colorectal tumor….pointed out, why would you treat with Gemzar, but it was what was available in the lab.

If you treat with Reolysin you get some benefit, if you treat with Gemzar by itself you see very typical for Gemzar, which is a suppression of tumor growth until you quit treating, which is the second arrow, and then it takes off.

And when you combine the two ….percent of the animals don’t have tumors anymore and 99.5 to 99% that are also durable. We see this with virtually every drug. Combined with the taxines, combined with any of the platinum group, Gemzar, you see the same thing with radiation. It’s really striking especially when you do the math and do the coefficients. The levels of synergy that you see with this agent with existing therapeutics.

Just quickly for data, we trade both on NASDAQ and Toronto. Our shareholder base is pretty much evenly spread between the US, Canada, and Europe. Which is what you would expect given that much of our work is done in Europe and the United States. And we have cash until Q2 ’09 with our anticipated programs.

Quickly and in summary, we’ve finished our first six studies, we have now have seven studies of on own ongoing, in the UK and the US, and the two NCI studies will be on top of that. We will finish most of those phase II components in 2008, and then move to pivotal programs later next year. Every single study we’ve had, has had clinical responses, and virtually consistent tox data, which is reassuring. Our IP bases is developing nicely. And as I said earlier, we have the resources to do all what I talked to you about today….And I know it’s kind of nerdy, but I like manufacturing…so we can actually produce this at a commercial scale at a cost that is about in a range of about 2% cost of goods at the 100L scale, which it will go down off of that, which for a biologic is somewhat amazing. I mean biologics don’t really cost that little. So we’re quite pleased with that. So I would just like to thank you for your attention.

Thursday, November 29, 2007

Oncolytics Biotech Inc. to Present at Annual Vaccine Production Conference

Wednesday, November 28, 2007

Oncolytics Biotech Inc. Announces Issuance of 24th U.S. Patent

Saturday, November 24, 2007

Article: Oncolytics Biotech working to uncover a Cancer Killer

Wednesday, November 14, 2007

Transcript: Acumen BioFin Rodman & Renshaw 9th Annual Healthcare Conference, November 6, 2007

Thursday, November 8, 2007

Oncolytics Biotech Inc. to Present at BIO-Europe 2007

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