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NCIC-CTG sponsors Randomized Phase II Prostate Cancer Study
CALGARY, Feb. 21, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) announced today that it has entered into an agreement whereby the NCIC Clinical Trials Group (CTG) at Queen's University in Kingston, Ontario, will sponsor and conduct a randomized Phase II study of REOLYSIN® in patients with recurrent or metastatic castration resistant prostate cancer.
"Third party sponsored trials remain an important part of our overall clinical strategy. We are pleased to be conducting another randomized study, especially in Canada, with an experienced and capable group like the NCIC CTG," said Dr. Brad Thompson, President and CEO of Oncolytics. "This study will build on both our early preclinical and clinical prostate cancer work, as well as our growing understanding of REOLYSIN in combination with approved chemotherapeutic agents. As a Company we continue to expand our clinical program to include studies of frequently diagnosed cancers."
The study will be an open-label, randomized, non-blinded, Phase II clinical study of REOLYSIN given in combination with docetaxel versus docetaxel alone. Approximately 40 response evaluable patients will be enrolled in each arm.
About Prostate Cancer
The Canadian Cancer Society estimates that 25,500 Canadians were diagnosed with prostate cancer and nearly 4,100 Canadians were expected to die from the disease in 2011. The prognosis for patients diagnosed with prostate cancer varies but the five-year survival rate for the period between 2004 and 2006 was approximately 95%.
About the NCIC Clinical Trials Group at Queen's University
The NCIC Clinical Trials Group (NCIC CTG) is a cancer clinical trials cooperative group that conducts Phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is a national research program of the Canadian Cancer Society. The NCIC CTG's Central Office is located at Queen's University in Kingston, Ontario, Canada. The Group is committed to assessing all modalities of therapy for a spectrum of cancer types. More than 60 member institutions, from major cancer centres to community hospitals, enroll patients in NCIC Clinical Trials Group studies.
P1 Relapsed/Refractory Multiple Myeloma clinical trial started
http://www.clinicaltrials.gov/ct2/show/NCT01533194?term=reolysin&rank=11
Run from the Arthur G. James Cancer Hospital & Richard J. Solove Research Institute an sponsored/paid for by the US National Cancer Institute.
Enrollment planned for 12
Detailed Description:
OBJECTIVES:
Primary
Determine safety and tolerability of wild-type reovirus (Reolysin) in patients with relapsed multiple myeloma.
Obtain evidence of reovirus replication by immunohistochemical co-localization of reovirus and tubulin staining in marrow clot sections obtained on course 1 day 8.
Secondary
Obtain preliminary data on response as determined by International Myeloma Working Group (IMWG) criteria after infusion of Reolysin as a single agent.
Obtain pilot overall and progression-free survival data for all treated patients.
Assess neutralizing anti-reovirus assay (NARA) results on days 1, 8, 15, and once on days 22-28 during course 1. (exploratory)
Assess feasibility of staining for RAF/MEK/ERK in CD138+ cells using marrow clot sections obtained from pre-treatment specimen. (exploratory)
Cryopreserve peripheral blood mononuclear cells (PBMCs) for future ancillary studies focused initially on lymphocyte subset(s) and myeloid-derived suppressor cell changes after Reolysin infusion during course 1. (exploratory)
Cryopreserve CD138+-selected cells at screening and after treatment for future ancillary studies of genetic and epigenetic changes focused in part on endoplasmic reticulum (ER) stress. (exploratory)
OUTLINE: This is a dose-escalation study.
Patients receive wild-type reovirus IV over 60 minutes on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow aspirate at baseline and periodically during study for RAF/MEK/ERK expression and wild-type reovirus replication analysis by immunohistochemistry. Blood and cryopreserved CD138+ selected cell samples are also collected for future ancillary studies.
After completion of study treatment, patients are followed up for 4 weeks and then every 6 months thereafter.
Financing Closes -Total Gross Proceeds of Cdn$21.3 Million
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-Closes-cnw-1315996060.html?x=0
CALGARY, Feb. 8, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX:ONC, NASDAQ:ONCY) today announced that it has closed its previously announced Cdn$18.5 million financing in which it entered into a revised agreement with a syndicate of underwriters, led by Paradigm Capital Inc., and including Canaccord Genuity Corp., RBC Capital Markets, Bloom Burton & Co. Inc., and Byron Capital Markets Ltd., (collectively the "Underwriters"), pursuant to which they purchased, on a bought deal basis, 4,405,000 common shares (the "Shares") of the Company at a price of Cdn$4.20 per Share for gross proceeds to the Company of approximately Cdn$18,501,000 (the "Offering").
In connection with the Offering, the Underwriters have exercised in full an option (the "Over-Allotment Option") to purchase an additional 660,750 Shares sold under the Offering at a price of Cdn$4.20 per share, on the same terms and conditions as the Offering. With the Over-Allotment Option exercised in full, the aggregate gross proceeds of the Offering to Oncolytics are approximately Cdn$21,276,150.
"The completion of this financing puts Oncolytics in a favorable financial position to fully fund our Phase III trial in head and neck cancers, broaden our clinical trial program for REOLYSIN® by supporting other indications, and continuing product validation activities," said Dr. Brad Thompson, President and CEO of Oncolytics.
The Shares were offered in Canada by way of a shelf prospectus supplement to a short-form base shelf prospectus dated June 10, 2010, that has been filed in the provinces of British Columbia, Alberta, Manitoba and Ontario pursuant to National Instrument 44-101 and National Instrument 44-102.
Oncolytics intends to use the net proceeds from the Offering to fund its ongoing Phase III combination REOLYSIN and paclitaxel/carboplatin trial for patients with platinum-failed head and neck cancers, its other clinical development and research and development activities, including manufacturing, and for general corporate and working capital purposes.
Casey Research - Us vs Cancer Reovirus Mention
Thanks to botinsel - Mention of Reovirus
http://www.caseyresearch.com/cdd/there-will-never-be-cure-cancer
Us vs. Cancer
By Alex Daley and Doug Hornig
That sounds like a pretty gloomy forecast, doesn't it?
It isn't, though, not really. Because the key word in that sentence is "a." There won't be a cure for cancer. But there will be cures for cancers.
In common parlance, "cancer" is understood as any kind of abnormal cell proliferation over which the body fails to exert control. But this means it is haphazardly applied to over 200 different diseases with some basic similarities – cancerous cells all grow, invade, erode, and destroy surrounding normal tissue –but which have a wide variety of causes, symptoms, and appearances, and which each require distinct care and treatment.
Thus, when fighting cancer at the biological level, you have to treat nearly every cancer differently… and very carefully.
(In professional circles the preferred term for this group of disorders has become oncological diseases, but for practical purposes we'll continue to use the more common, singular form of the noun.)
Cancer is tough to treat because of what it isn't. There is no virus or bacterium that directly causes it. You can't "catch it" from another person or an unclean surface or through the air. Environmental factors may play a role, but again, they are not causative. Cancer is a disease of the genes. It happens when our own bodies turn on us, when some kind of genetic malfunction allows cells to proliferate wildly, uncontrollably, and unstoppably.
Normally, our bodies are nicely equipped to keep our cells humming along. We have both growth-promoting genes, which ensure healthy cellular reproduction, and growth-suppressing genes, which keep that reproduction in check. It's a delicate balance, though; and unfortunately, either of these can go haywire. In both cases – if growth-promoters become overly enthusiastic about their job or if growth-suppressors fail to do theirs –the result is the same: cancer.
Up to now, all treatments that kill cancer cells cause collateral damage to healthy tissues of the body. But that is poised to change.
In the long run, conquering a genetic disease means discovering a cure that works at the genetic level. We're getting there. Decades of research are just now beginning to bear fruit, and the result will soon be a revolution in cancer therapy – a revolution that will not only save countless lives but will create incredible wealth for the scientists and companies involved and those who invest in them.
Not that we haven't already made substantial progress. For example, 90% of breast cancer victims survive for at least five years if diagnosed after 2001, compared with only 75% as recently as 1975-77. And with prostate cancer, five-year survival has rocketed to fully 99% of those diagnosed in the past ten years, vs. 68% in the mid '70s.
The raw number of US cancer survivors – defined as anyone who has been diagnosed with the disease but remains living – is on the rise as well. That figure was three million in 1971; it more than tripled to 9.8 million in 2001; and it further increased to 11.7 million in 2007, with seven million aged 65 or older. These numbers far outstrip demographics; the near-quadrupling of cancer survivors from 1971-2007 happened against the background of just an 80% increase in the over-65 population. The cancer diagnosis is not the all-but-automatic death sentence it once was.
These statistics are encouraging. But they've been achieved with medical techniques that will one day be looked back on as exceedingly crude: "slash, burn, and poison," as detractors term the standard triumvirate of surgery, radiation, and chemotherapy.
Each of these separately or in combination carries risks and side effects that are on the serious side – ranging from highly uncomfortable through barely tolerable to outright lethal. It'd be nice to have something in the toolkit that is not as potentially hazardous as the disease itself. It would be even better if that something worked dramatically, not just incrementally, better. Until recently, such treatments have eluded us. Now though, gene-based, targeted therapies have arrived.
Slowly, we're moving from an understanding of what composes the genetic structure – thanks to the Human Genome Project – to understanding how it works in a dynamic system. As we begin to get it, we can start looking for an answer to the question of what to do when things go wrong.
It sounds so straightforward when expressed like that. However, it's anything but. There are tens of thousands of scientists at work worldwide seeking a cure. To find it, they're testing hundreds of different approaches, most of which were science fiction just a few years ago. It's a full-out sprint to the finish line, nothing spared. Not money, not time, not talent – because fame and fortune await the winners.
But there are stumbling blocks. The scene in today's labs was pretty well summed up by the title of a recent Forbes article: Cancer's New Era of Promise and Chaos. "Promising" because of the amount of genetic decoding that has already been done, and the breathtaking speed at which further research is proceeding, but "chaotic" because the more we learn, the more complex the problem is revealed to be.
In a brief article such as this, it is impossible to cover all of the research being done on cancer or to provide in-depth coverage of any of them. But in general, nearly everyone is working on a targeted therapy of some kind, i.e., something that homes in on cancer cells while sparing healthy cells the damage caused by surgery, radiation, or chemo.
Our knowledge of these diseases is progressing at a remarkable rate. (If you have some technical expertise, this extensively detailed paper is a good summary of the present state of our knowledge… though, like any publication in a field moving this quickly, it becomes just a little more out of date with each passing day.) And the approaches to treating it are evolving just as quickly.
Following in no particular order are some highlights of new treatment techniques that are either already here, in human clinical trials, or just over the horizon. Some are probably stopgap measures, variants of current therapies to employ until it becomes possible to simply silence bad genetic information. None of them purports to be effective against all cancers, or even applicable to all people with the same cancer. There are undoubtedly some we've overlooked. And tomorrow's headlines could well trumpet some breakthrough no one knows about yet.
Already Here
Hormone therapy. Certain natural hormones assist some cancers to grow, and in these instances the proper medication can interfere with the activity of the hormone or stop its production.
Proton therapy, one of the most promising near-term replacement possibilities for traditional radiation, directs beams of protons (instead of X-rays) at a tumor. It has a tighter beam that can be controlled in three dimensions, meaning a lot less lateral scatter than X-rays and no need to pass the beam through tissue behind the target area, thus eliminating much damage to surrounding, healthy tissue. See the Casey Research article on the subject.
Liposomal therapy takes existing chemotherapy drugs and packages them inside liposomes (synthetic fat globules). The liposome helps the drug penetrate the cancer cells more selectively and decreases possible side effects.
Biologic therapy (also called biotherapy and immunotherapy) is a catchall category of treatments that attempt to produce antitumor effects primarily through stimulation of natural host defense mechanisms or by the administration of natural or manmade immune system components.
Angiogenesis inhibitors prevent the formation of new blood vessels so that tumors cannot grow. They are well tolerated, not toxic to most healthy cells, and can be applied to cancer that is metastasizing.
Thermal High Intensity Focused Ultrasound (HIFU) uses ultrasound to raise the temperature within the target to 65° to 85°C, destroying the diseased tissue by coagulation necrosis. It's in limited use today to treat a few primary cancers, notably prostate cancer. HIFU's long-term effectiveness is still in question.
Radiofrequency ablation (RFA), also in general use today, involves the insertion of a thin needle, guided by computed tomography (CT) or ultrasound, through the skin and into the tumor. Electrical energy delivered through this needle heats and destroys the cancer cells.
Monoclonal antibodies (MAbs) are cloned from a unique parent. Naked monoclonal antibodies (MAbs without any drug or radioactive material attached to them) have been used to treat cancer for more than a decade by binding to specific antigens and acting either as markers for destruction by the body's immune system or blockers of activation and continued growth of certain cancer cells. More recently, conjugated MAbs (those joined to a chemotherapy drug, radioactive particle, or cytotoxin) have come onto the scene. Seattle Genetics' recently approved drug Adcetris is a particularly promising conjugated MAb.
In Clinical Trials
Telomerase therapy. Malignant cells continue to grow because apoptosis (cell death), the fail/safe mechanism of cellular chemistry, is turned off, and their chromosomes will not become unstable no matter how many cell divisions they undergo. The faulty action of an otherwise useful enzyme called telomerase facilitates this, giving cancer a kind of immortality. A drug which inactivates telomerase might be effective against a broad spectrum of malignancies.
Molecular targeted therapy targets molecular components within the cell-signaling pathways that support tumor survival and growth. The goal is to disrupt cell duplication (i.e., tumor growth) and promote cancer-cell death.
Reovirus (short for Respiratory Enteric Orphan virus) therapy involves five days of intravenous injections with a proprietary variant of a virus found in nature. This virus feasts on cells with a particular characteristic – the activation of the Ras pathway – which promotes growth if it's turned on, as it is in 2/3 to 3/4 of cancer cells. Side effects are few and minimal. If all goes well, the reovirus could be marketed as early as 2012.
On the Horizon
RNAi (RNA interference) is particularly exciting because it's true genetic medicine, applied right where cancer begins. It involves "turning off" messenger RNA that is carrying bad genetic information before that RNA can do its harm. At the moment, RNAi research has been directed primarily at other genetic abnormalities, and its potential use in cancer treatment is largely unexplored. But it will be. For a closer examination of RNAi, see the special Casey Research report Kill the Messenger.
Nanobubbles are another experimental delivery system. One technique currently being tested on animals delivers anticancer drugs in packets of nanoparticles to the tumor, where they accumulate. Ultrasound can then be directed at the target, popping the bubbles and releasing the drug within a well-defined area. A second, unrelated line of research uses antibodies to deliver a packet of gold nanoparticles to the cancer cell. An intense, focused laser beam is then used to explode the nanobubble, bursting the cell.
Mechanical High Intensity Focused Ultrasound, a second variant of HIFU, is in the early experimental stage. It delivers the ultrasound in a manner that just shakes the tumor cells, rupturing their membranes, causing them to spill their contents. The toxic spill then alerts the immune system, leading to the production of tumor-fighting white blood cells.
Hyperthermia therapy. All these treatments are highly experimental, as researchers explore a number of different ways of delivering a lethal amount of heat to the target. Among the possibilities: microwave heating, induction heating, magnetic hyperthermia, and the direct application of heat through the use of hot saline solution pumped through catheters. Tests also have been conducted with carbon nanotubes that selectively bind to cancer cells. Lasers are then used that pass harmlessly through the body but heat the nanotubes, causing the death of the diseased cells.
Way Out There
Everyone loves the idea of microscopic robots patrolling the human body in search of problems. Since they were first envisioned, these nanobots have been regarded as the potential holy grail of cancer treatments. The idea of a multitude of miniscule robots in the bloodstream armed with a multitude of payloads to combat all sorts of different diseases, happily chewing up every compromised cell before it can do any harm, is very compelling. That dream, however, remains a long way off.
However, in an interim technique presently being studied, 70-nanometer attack bots – made with two polymers and a protein that attaches to the cancerous cell's surface – carry a piece of RNA called small-interfering RNA (siRNA), which deactivates the production of a protein essential to malignant growth, thus starving the cancer cell to death. Once its job is done, the nanoparticle breaks down into tiny pieces that are simply flushed away in the urine. This would bring all the benefits of RNAi without the complications coming to light in trials with traditional delivery mechanisms.
The Opportunity for Investors
Right now, the majority of the advanced techniques we've mentioned above are either in the late stages of laboratory testing, about ready to be deployed in the first few human patients, or already being studied in hundreds of cancer victims. Major pharmaceutical companies, venture capital firms, university research labs, nonprofits, and individual biotechnology entrepreneurs are pouring billions of dollars into the sector every year.
But how do you know whom to back?
Of course, there is no certain way to separate the winners from the losers ahead of time – and there will be multiple examples in both categories as this race progresses. However, it is possible to increase the likelihood of success. Here is a brief primer:
Always bear in mind that this is a high-risk/high-reward sector. Fortunes can shift in a heartbeat. Large investors line up their bets early, backing some early-stage companies more heavily than others. But unexpected results from a clinical trial can quickly topple an early favorite or give rise to a dark horse. Depending on your tolerance for risk, decide where you wish to invest along the development curve, from early-stage exploratory research to products already in the market.
Conduct your own self-education. You'll need some basic grounding in physiology. You'll have to acquaint yourself with what is and isn't cutting edge tech and understand the investing implications of backing technology that could take months, years, or even a decade or more to come to market. And you'll have to develop the ability to parse trial results. For instance, it is critical to be able to distinguish between a negative test result that is merely a temporary setback and one that means curtains for the drug candidate (and thus often the company). If you can't do all this on your own, at least find a trustworthy guide.
Learn about the team. Within many technology silos there will be more than one company doing similar research. It's important to understand not only the technical differences among their approaches but the value of their teams as well. Many of the best technologies fail to reach the market simply because of bad management – nowhere is that the case more often than in biotechnology, where companies must manage massive research spending and plan for huge cost contingencies, often for years before seeing revenue. You'll want to learn the ins and outs of the approval process and the costs associated with each step to assure yourself that management is spending wisely and you won't be diluted too badly in the event a contingency plan has to go into effect.
Develop a confident trigger finger. Once you have figured out what technologies are the best bets for your investing dollars, you must be able to pull the buy/sell trigger on a given investment dispassionately and without hesitation. In order to generate the really big returns, you must be invested ahead of the crowd, before the potential payoff is already baked into the share price. And you must be quick to sell when the moment is right.
Don't jump in too early. Retail investors should usually look for are companies that have produced some promising results in real-world tests, but are still short of Phase III success (typically the last major stage before commercialization), the point at which the "limited risk" crowd will be rushing to board the train. Those are the people, mostly larger investors, who either have reluctance to, or are specifically prohibited from, taking too much of a chance, and who instead seek "safe" 10% or 20% gains. Buy in before they get there. It's to them that you, as a mid-stage investor, will sell your stock.
Check the pipeline. You usually want to select companies that are more than one-trick ponies. Any company staking everything on a single drug candidate is a very risky investment. One strike and they are out. There are times when the potential payoff is enticing enough to make these investments worthwhile, but far more preferable are companies that have a handful of therapies in the testing pipeline… or better still, ones that have developed a unique platform from which they can launch multiple products.
Check the pipeline again. At the same time, watch that your company is not spread too thin. Obsession with the pipeline at the expense of getting drugs to market in a reasonable timeframe can easily lead to running out of cash, a potentially deadly event that has taken down many a biotechnology company.
Hedge your bets. In a field as complicated and diverse as cancer research, you really have no choice. If you stock your portfolio with several companies, all of them pursuing different experimental lines, you greatly enhance your likelihood of success.
The same of course is true for cancer. The more treatments there are available, the more likely it is that patients can beat the diseases. So, while there may not be a cure for cancer, there will be many. And with the right strategy, they very well might help your portfolio heal a bit too.
[The Casey Extraordinary Technology biotech portfolio features later-stage, cancer-centric companies involved with RNAi, monoclonal antibodies, and molecular targeting. Learn more about our cancer fighting portfolio.]
Bits and Bytes
First 3D Chip (PhysOrg)
To date, all computers have been built upon a two-dimensional model. Increases in power have depended on increasing the number of circuits that can be crammed on the single plane that is the surface of a chip. It's worked well so far, but there are obviously physical limitations to how small you can shrink those circuits. Even linking chips side by side doesn't increase efficiency much. The next generation may therefore have to reach in a different direction – into the third dimension. That is, why not create chipstacks that are connected so that electrical impulses can flow up and down as well as across the chip? Though it sounds simple, there are a lot of technical hurdles that have flummoxed researchers for many years. The problems may now have been resolved, however, due to this breakthrough joint effort announced a month ago by IBM and Micron Technologies. The day of 3D chips is dawning.
Smallest 3D Printer (TEDxVienna)
And while we're on the subject of 3D, subscribers to Casey Extraordinary Technology already know how bullish we are on the burgeoning field of additive manufacturing, or 3D printing. These machines are rapidly getting better, cheaper, and more versatile. They're also getting smaller, as you can see.
Does Google Want It All? (The Week)
Well, the search-engine giant is coming hard after the browser market. It's not likely to catch Internet Explorer (IE) anytime soon, since that's the default on Windows-based computers and most users don't bother with anything else. Among those who do want something different, the most appealing alternative has for a long time been Mozilla's Firefox. No longer. Google's Chrome raced past Firefox in market share for the first time in November. Many have now pronounced Firefox a dead man walking. Is IE next?
Chrome has been a smashing success, and Android has been torching the mobile market. Next up in Google's gunsights: the almighty iPad. The company goes to war with Apple again early this year, as it launches its first tablet at about the same time as the arrival of iPad3. It's a risk for Google, but that's never been a deterrent… not when you want it all.
Nano Goes Big (Technology Review)
Carbon nanotubes, one of the wonders of nanotechnology, are just a few billionths of a meter wide, and they're among the strongest and most conductive materials known. Scaling them up to make functional products is a challenge, but some cutting-edge companies are already deeply involved. Most people have probably never heard of nanotubes. That will change, and soon.
Dr Gerald Kennealey appointed SVP Clinical Development/CMO
11/10/2011 8:03:36 AM ET
Oncolytics Biotech Announces Appointments to Senior Management Team
CALGARY, AB, November 10th, 2011 --- Oncolytics Biotech Inc. (TSX:ONC, NASDAQ:ONCY) (“Oncolytics”) today announced the appointment of Gerard Kennealey, MD as Senior Vice President of Clinical Development and Chief Medical Officer (CMO). George M. Gill, MD, Oncolytics’ CMO since July 2011, will return to his previous role as Senior Vice President of Regulatory Affairs and also has been appointed Chief Safety Officer.
“Dr. Kennealey is an excellent addition to our clinical development team bringing extensive experience with new oncology drug submissions, regulatory reviews and clinical trial management to his new role,” said Dr. Brad Thompson, President and CEO of Oncolytics. “Dr. Kennealey and Dr. Gill form a strong team that will advance our proprietary product, REOLYSIN®, through late-stage clinical testing and global regulatory approvals.”
Dr. Kennealey holds a B.S. (Biology) from Boston College and an MD from the Yale University School of Medicine. Following his medical training and a decade as a practicing oncologist, Dr. Kennealey worked for AstraZeneca where he held positions including Vice President, US Medical Affairs; Vice President, Oncology Clinical Research; and Global Product Director for Faslodex®. Dr. Kennealey subsequently held an array of progressively senior positions with other companies in the life sciences industry, as Senior Vice President & Chief Medical Officer at Eximias Pharmaceuticals; Senior Vice President, Drug Development at MGI Pharma; and Vice President of Business Development at Cephalon Inc. Most recently, Dr. Kennealey was Vice President of Scientific Affairs at Cephalon Inc.
Dr. Gill holds a B.Sc. (Chemistry) from Dickinson College and an MD from the School of Medicine of the University of Pennsylvania, and is board certified in pediatrics. He began his career in the pharmaceutical industry at Hoffman-La Roche, where he held a variety of positions, including as Director of the Clinical Oncology Group and Associate Director of Regulatory Affairs. He was subsequently Vice President of Clinical Research and Vice President of Medical Affairs at Ligand Pharmaceuticals; Senior Director and Head of U.S. Clinical and Medical Affairs for ICI Pharmaceuticals (now AstraZeneca); and Vice President and Head of Worldwide Regulatory Affairs for the Bristol-Myers Company (now Bristol-Meyers Squibb). Dr. Gill joined Oncolytics in 2002.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
This press release contains forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company’s control and which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or expectations implied by these 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, except as required by applicable laws.
FOR FURTHER INFORMATION PLEASE CONTACT:
The Equicom Group
Nick Hurst
300 5th Ave. SW, 10th Floor
Calgary, Alberta T2P 3C4
Tel: 403.218.2835
From Dr Keenealy's LinkedIn profile,
Gerard Kennealey's Summary
"I am a Board Certified medical oncologist and currently am VP of Business Development at Cephalon. I have 23 years of industry experience at small, medium-sized and 'big pharma' companies as well as independent consulting.
While at AZ, i started the Expanded Access Program for Iressa which ultimatley enrolled >20,000 patients with lung cancer. I have given many talks on EAPs and am interested in consulting with companies that wish to consider instituting an EAP
I am very interested in being considered for Board of Director positions at small to medium sized pharma/biotech companies where my drug development expertise in oncology and related fields would be of benefit.
Specialties
IND and NDA submission, design of clinical trials, critical review of clinical development plans, development of Expanded Access Programs"
Dr Thompson at World Gene Therapy Congress London
Invited/Scheduled to speak Wed May 23, 2012 at 9:10 AM during Day 2 session titled The Potential of Viral Therapy
http://www.terrapinn.com/conference/gene-therapy-congress/programme-day-2-wednesday-23rd-may-2012.stm
Dr Thompson's program is titled Tactics for killing the tumour while protecting the body
30 Minutes
Interesting this May 23rd presentation is scheduled 1 week after ASCO 2012 abstracts are published online - May 16th 2012.
http://chicago2012.asco.org/AttendeeInformation/KeyDates.aspx
ASCO 2012 in Chicago is running June 1-5 so this London presentation looks to be fit just between when ASCO abstracts are published and the actual ASCO meeting.
Oncolytic viruses: smart therapeutics for smart cancers
http://www.futuremedicine.com/doi/full/10.2217/fon.11.134
Rebecca Auer & John C Bell*
* Author for correspondence
In his 2011 American Society of Clinical Oncology (ASCO) Presidential Address, George Sledge (Indiana University Melvin, IN, USA) argued that cancers can be classified as ‘stupid or smart’ depending upon their mutational load. His thesis was that ‘stupid’ cancers have a single dominant mutation (e.g., CML and BCR-ABL) that can be effectively treated by targeting the key oncogenic protein with a single small molecule (e.g., imatinib/Gleevec®, Novartis Oncology, USA). Unfortunately, most patients suffer from ‘smart’ cancers, which are tumors with multiple ‘driver’ mutations, each one requiring its own specific inhibitor in order to potentially reverse the malignant phenotype. To improve outcomes for patients infested with smart cancers requires the development of ‘smart therapeutics’ – treatments that attack cancers in multiple ways. We argue that oncolytic viruses (OVs) are smart therapeutics and, indeed, through genetic engineering can have their ‘IQs’ raised by several points.
Preying upon activated signaling pathways
OVs are replicating therapeutics that are engineered to grow in tumor cells but are unable to productively infect normal tissues [1,2]. OVs are smarter than small molecules because, rather than trying to inhibit a single oncogenically activated pathway, OVs prey upon entire malignant signaling networks that drive the cancer phenotype. The replication of OVs is strictly dependent upon the malignant activation of cell signaling pathways in tumor cells such that cancer driver mutations are also OV driver mutations. The addiction of OVs to overactive cell signaling means that individual driver mutations in a cancer (e.g., EGF receptor [EGFR] and KRAS) are not as important to the viral therapeutic as the overall pathway activation state. Lee et al. [3] found that, in a lung tumor from a single patient, there were a large number of mutations in the cancer genome, many of these leading to overlapping, redundant activation of the EGFR and parallel pathways. Single molecular targeting of any one of these mutations will not provide therapeutic benefit to the patient. By contrast, clinical OVs, such as vaccinia virus (JX-594, Jennerex Biotherapeutics, CA, USA) or reovirus (Reolysin®, Oncolytics Biotech, Alberta, Canada) require activation of the EGFR pathway to efficiently replicate [1,4]. To the virus, the type or number of activating mutations is irrelevant – as long as there is at least one, the virus will be able to carry out its replicative cycle. Once the virus initiates infection within a tumor cell, it elaborates a series of ingenious viral proteins that usurp the cell’s metabolic machinery. The co-opting of transcriptional and translational machinery by the virus means that the infected cell will be unable to support its own basic functions and succumb, liberating OV particles that can move on to the next tumor cell.
Smart cancers are not altruistic
Tumor cells, in their quest for immortality, have found ways to overcome or attenuate their apoptotic programs. Normal cells have functional apoptotic programs with multiple roles but one important use of this pathway is to block virus spreading during the course of an infection. In this respect, normal cells are ‘altruistic’, preferring to ‘commit suicide’ following infection in order to blunt virus growth and protect their neighbors. Many pathogenic viruses encode inhibitors of apoptosis, allowing them to productively infect normal tissues and circumvent cellular antiviral programs. OVs are engineered to have mutations in antiapoptotic functions and, thus have a limited capacity to productively infect normal tissues. Cancer cells are not altruistic and, since they have eliminated their apoptotic programs, are powerless to resist OV infection and spread.
OV tumor targeting & self-amplifying dosing
One challenge to the treatment of metastatic cancer is delivery of an optimal therapeutic drug dose to all the sites of disease within the patient. Large concentrations of the drug must be delivered intravenously to reach the tumor bed, but, even then, high interstitial pressure or poor tumor perfusion can prevent drugs from reaching their intended target [5]. For most drugs there are no mechanisms of selective delivery and so the patient must be effectively saturated with the therapeutic to achieve beneficial concentrations within the tumor.
An OV can be engineered to specifically recognize either the tumor cell surface [6] or the tumor vascular endothelium [7], facilitating selective delivery. For many OVs in clinical development, targeting is not at the cell surface but rather determined by malignantly activated intracellular signaling pathways [1,8]. Regardless of the mode of delivery to the tumor bed, because OVs are self-replicating biological machines, they can copy their genetic information, express virally encoded proteins and self-assemble, generating more therapeutic viral particles in situ. In principle, only a handful of OV particles needs to infect a tumor for self-amplification to occur, creating an army of viral parasites that spread throughout the tumor. In reality, clinical data suggest that as many as several thousand viral particles need to seed a tumor before the OV can successfully spread [9]. Many of the barriers to drug entry into the tumor exist for virus particles; however, some innate OV characteristics and other traits that can be engineered into the virus can lead to more effective therapeutic spread. Some OVs spread via cell–cell contact and/or fusion, thus mitigating interstitial pressure concerns. For highly fibrotic cancers, where tumor nests are encased in extracellular matrix, new OVs are being developed that encode proteases, allowing the virus to burrow between tumor beds [10,11].
OVs have learned to navigate the perils of the bloodstream
Barriers to the delivery of therapeutic viruses to metastatic tumors via the vascular system include immune cells, antibodies, complements, and a variety of scavenger cells that line the endothelium of vessels in the liver and spleen. Viruses have evolved strategies to overcome many of these barriers. For instance, viruses have turned the tables on their mammalian hosts and ‘ride or hitchhike’ on the very immune cells meant to target them in order to gain carriage into tumor beds [12,13]. Sometimes, the hitchhiking virus is protected from neutralizing antibodies in the circulation by this cell association. Some OVs encode inhibitors of the complement system within their genomes to overcome this barrier [14]. Poxviruses not only encode complement inhibitors, but also create multiple viral isoforms, including a ‘cloaked or stealth’ version that can avoid antibody neutralization and enhance virus spread [14]. The demonstration of dose-dependent delivery of OVs to tumors in cancer patients after intravenous administration demonstrates that at least some of the barriers found within the bloodstream can be overcome simply by using ‘saturating’ doses [9].
Targeting tumor vasculature
Any clever General knows that a simultaneous direct frontal assault is more effective when the enemy’s supply lines have been cut off. OVs use this strategy to aid in the attack upon their tumor foes. OVs, either through genetic engineering [15] or as part of their natural biology [16], have the capacity to specifically infect and destroy tumor blood vessels. Engineered viruses have been created that simultaneously recognize the surface antigens of tumor vessels and tumor cell receptors. This affords them the opportunity to productively infect and destroy the vascular pipeline that feeds the cancer, while also wreaking havoc on the tumor by direct infection [17]. Many natural viruses have evolved mechanisms to infect endothelial cells as part of their natural pathogenic program. Some of these viruses can be selected or engineered to become oncolytic, and, thus have the ability to infect both their ultimate target, the tumor and the tumor’s associated blood vessels. In these cases, the selectivity for tumor vasculature is not at the cell surface but rather it exploits signaling pathways that are malignantly activated in the tumor microenvironment. In experimental mouse models, the infection of tumor vasculature leads to the specific formation of microclots that, remarkably, are completely restricted to the malignancy [16,18]. These intravascular clots cause a catastrophic loss of blood flow into the tumor and initiate massive cancer cell death, even in uninfected areas. Therefore, while OVs directly infect and kill tumor cells, they also use this second strategy to kill throughout the tumor bed. The genius of this approach is that even if the tumor is somewhat refractory to OV infection, destruction of its supporting vasculature could still lead to good therapeutic outcomes.
Smart viruses expose stealth tumors to the immune system
In their recent update of the ‘Hallmarks of cancer’, Hannahan and Weinberg include immune evasion as a key property of the successful malignancy [19]. While smart tumors mutate multiple signaling molecules/pathways to gain a growth advantage, in doing so, they may also generate a vast array of new tumor antigens that can be potentially recognized by the patient’s immune system. It is now clear that smart tumors adapt a variety of different strategies to hide from immune surveillance programs, which are active in all of us. Tumors downregulate self-surface MHC molecules, secrete immunosuppressive cytokines to paralyze immune effector cells and dampen innate immune responses that are incompatible with rapid and unlimited cell growth. When OVs initiate tumor-specific infections, they trigger localized inflammatory reactions [18]. This inflammatory cascade uncloaks the stealth tumor and leads the patient’s immune response right to the offending tumor bed. In animal models, there is no doubt that activation of antitumor immune responses is an important component of the therapeutic benefit of OVs [20]. This is also likely to be true of clinically relevant OVs, such as JX-594 [21], and the Amgen (CA, USA) product OncoVEX, which is being coined an oncovaccine. The antitumor immune responses triggered during oncolysis by the OncoVEX product are truly remarkable and lead to durable responses in a significant portion of melanoma patients [22]. In general, it is felt that immune responses to viruses are likely to curb the effectiveness of OV therapeutics. Given that smart tumors create a zone of immune suppression in their microenvironment, they may be playing into the hands of OVs by providing them with an immune sanctuary where the virus can also remain, at least transiently, invisible to the patient’s immune system.
What is good for the tumor is good for the OV
Herein, we have provided examples of how the mutated pathways that promote tumor growth also create an environment that favors OV replication. OVs are easy to engineer and, as we learn more about how cancers evolve and become genetically unique from their normal counterparts, it will be possible to further enhance OVs, allowing them to become formidable smart therapeutics. OVs have the potential to become effective anticancer therapeutics and certainly the clinical data to date suggest that they may be amongst the safest therapeutics currently in clinical use and/or testing.
Financial & competing interests disclosure
J Bell is a cofounder and on the Board of Directors for Jennerex Biotherapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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17.Ong HT, Trej,TR, Pham, LD, Oberg AL, Russell SJ, Peng KW. Intravascularly administered RGD-displaying measles viruses bind to and infect neovessel endothelial cells in vivo. Mol. Ther.17(6),1012–1021 (2009). [CrossRef] [Medline] [CAS]
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Affiliations
Rebecca Auer
Ottawa Health Research Institute Ottawa, Ontario, K1H 8L6, Canada. jbell@ohri.ca
John C Bell
Ottawa Health Research Institute Ottawa, Ontario, K1H 8L6, Canada. jbell@ohri.ca
RAS Pathway Explained
http://www.sabiosciences.com/pathway.php?sn=Ras_Pathway
Ras is a membrane-associated guanine nucleotide-binding protein that is normally activated in response to the binding of extracellular signals, such as growth factors, RTKs (Receptor Tyrosine Kinases), TCR (T-Cell Receptors) and PMA (Phorbol-12 Myristate-13 Acetate). Ras signaling affects many cellular functions, which includes cell proliferation, apoptosis, migration, fate specification, and differentiation. Ras acts as a binary signal switch cycling between ON and OFF states, which are characterized in terms of a small molecule, a guanine nucleotide, bound to the protein. In the resting cell, Ras is tightly bound to GDP (Guanosine Diphosphate), which is exchanged for GTP (Guanosine Triphosphate) upon binding of extracellular stimuli to cell membrane receptors. In the GTP-bound form, Ras interacts specifically with so-called effector proteins, thereby initiating cascades of protein-protein interactions that may finally lead to cell proliferation. To return to the inactive OFF state, Ras cleaves off the terminal phosphate moiety, the Gamma-Phosphate, of GTP in an enzymatic process, the intrinsic GTPase reaction. The remaining GDP-bound Ras is no longer able to interact with effectors, it is switched OFF. Ras is thought to activate a number of signaling pathways, including the Raf/MEK/ERK (Extracellular Signal-Regulated Kinases) pathway, the MEKK/SEK/JNK (Jun N-terminal Kinases) pathway, a PI3K (Phosphatidylinositol 3-Kinase)/Akt/NF-KappaB (Nuclear Factor-Kappa B) pathway, a p120-GAP/p190-B/Rac/NF-KappaB pathway, and a Raf/MEKK1/IKK (I-KappaB Kinase)/I-KappaB/NF-KappaB pathway.
Most growth factors that signal through RTKs or heterotrimeric GPCR (G-Protein Coupled Receptors) stimulate Ras by recruiting the GEF (Guanine-Nucleotide Exchange Factor) SOS (Son of Sevenless) to the membrane. SOS exists in a complex with the adapter protein GRB2 (Growth Factor Receptor-Bound Protein-2). Upon receptor activation, the GRB2/SOS complex is translocated to the membrane by binding of GRB2 to tyrosyl-phosphorylated residues in RTKs or additional adapter proteins. GTP-bound Ras recruits and activates Raf. Raf initiates a cascade of protein phosphorylation by first phosphorylating MEKs. Phosphorylated MEK in turn phosphorylates ERKs. Phosphorylated ERK moves from the cytoplasm into the nucleus where it subsequently phosphorylates a number of transcription factors, including the specific transcription factor called Elk1. Phosphorylated transcription factors turn on transcription (gene expression) of specific sets of target genes. The activity of Ras is limited by the hydrolysis of GTP back to GDP by GAP (GTPase Activating Proteins) (Ref.1).
A second effector is PI3K, which synthesizes several lipid second messengers that activate small G proteins such as Rac and CDC42 (Cell Division Cycle-42). Rac also has multiple effectors, one of which is the serine threonine kinase PAKs (p21 Activated Kinases). The PI3K-mediated survival signal is also triggered by the activation of Akt/PKB (Protein Kinase-B). The third and most recently established effector is the Ral guanine nucleotide exchange factor, RalGDS (Ral-Guanine Nucleotide Dissociation Stimulator). RalGDS is a GEF (Guanine Nucleotide Exchange Factor) for the small GTPase Ral. Currently, five Ral GEFs have been identified; RalGDS, Rgl, Rlf, Rgr and RalGEF2 that are direct targets for Ras (Ref.2). They provide a mechanism for Ral activation by extracellular signals via a variety of receptors, including GPCR and RTKs.
Reactive free radicals and cellular redox stress have been proposed to directly activate Ras. NO (Nitric Oxide) promotes the direct post translational modification of Ras by single S-nitrosylation at Cys118. These results in stimulation of guanine nucleotide exchange, possibly by destabilization associates with other effectors, leading to transduction of Ras mediated signals through multiple pathways. In addition to Raf, PI3K and RalGDS other Ras effectors have been proposed, including p120GAP, PKC-zeta, Rin1, AF6, and NF1 GAP (Ref.3). TCR engagement also leads to the activation of Ras via a signaling pathway involving the activation of p56 (Lck) and PKC (Protein Kinase-C). Biochemical and genetic studies have now confirmed the functional relevance of Ras effectors. The Raf protein kinase family controls the activation of the MAPK (Mitogen-Activated Protein Kinases) pathway and plays a major role in controlling proliferation and differentiation. The PI3K mediates some of the Ras-dependent actin cytoskeleton remodeling and protection against apoptosis. The third bonafide Ras effector is RalGDS, regulates multiple processes including receptor endocytosis, cytoskeletal changes, and DNA synthesis. The Ras-Raf-MEK-ERK pathway features several oncogenes and is deregulated in approximately 30% of all human cancers. It has also emerged as a prime target for antitumor therapy (Ref.4).
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Selective GRB2 SH2 inhibitors as anti-Ras therapy.
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The small-GTPase RelA activates transcription of the urokinase plasminogen activator receptor (uPAR) gene via an AP1-dependent mechanism.
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Diaz-Meco MT,Lozano J,Municio MM,Berra E,Frutos S,Sanz L,Moscat J.
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Positive Interim Phase II Pancreatic Trial Results
Murrstir
In this case interim results were released because the 33 patient trial met its goal after only 13 patients. This is quite a good result in an indication with such low life expectancy.
Your earlier question about general Phase III trial length is difficult to answer because of the variability of many factors... How many are planned to be enrolled, how tight the enrollment criteria is, how available are patients in the locations you are running trials and competition from other trials. Oncolytics has chosen to dramatically increase the centers running trials to speed up the enrollment. Unfortunately the CEO has not given updates to the number of enrolled patients so its very hard to predict how long until we reach the 80th patient in our Phase III H&N trial. If we have 60 centers enrolling, you only need 1.3 per center to reach 80.
After we reach 80 then we will most likely wait to open the data to allow the response time to be evaluated for the 80th patient which may be a few months, the the analysis which may take a few months. So the uncertainty of when we will get to see data remains today until we get the 80th patient enrolled press release.
The problem with waiting on the sidelines is that news of a partnership or some other unexpected positive event could move this very fast.
Next up is lung cancer, both NSCLC (Dr Villalona) and SCCL (Dr. Monica Mita) results are expected this year so that a decision can be made on a Phase III in one of these two indications... at least that is what the expectations were. How fast these trials are moving now is also uncertain as we have been given no recent updates beyond the July NSCLC results which brought to light the agonizingly slow pace of enrollment in NSCLC.
We also have Phase I colorectal results from Dr Sanjay Goel to see as well as Melonama from Dr Monica Mita at some point. The other panc trial using Carbotax has a while yet to go although this has the outside potential to be one trial that could be stopped early if they are seeing results like to Mayor Brennan.
As others have said we need patients and patience.
A summary of the trials can be found here... http://clinicaltrials.gov/ct2/results?flds=Xt&flds=a&flds=b&flds=c&flds=f&flds=g&flds=h&flds=j&flds=k&flds=l&flds=o&flds=p&flds=q&flds=s&term=reolysin&show_flds=Y
Does this help out at all?
onco_investor
US PhII H&N Abstract at AACR
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=3689430c-4df3-4d0e-a34c-692c209b1f10&cKey=da6a20b4-0498-4900-9466-057b7e45c07d&mKey=%7bA57FF86D-D414-4079-BCBD-157746574F37%7d
Abstract Number: C22
Presentation Title:
A phase II study of intravenous wild-type reovirus (Reolysin®) in combination with paclitaxel plus carboplatin in patients with platinum refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck
Location: West Hall, Level One, Moscone Center West
Poster Board Number: C22
Author Block: Anand B. Karnad1, Missak Haigentz2, Tracy Miley1, Matt Coffey3, George Gill3, Monica Mita1. 1CTRC, UT Health Science Center, San Antonio, TX; 2Montefiore Medical Center, Bronx, NY; 3Oncolytics Biotech Inc., Calgary, AB, Canada
Abstract Body: Purpose: REOLYSIN® (Reovirus serotype 3) is a Dearing strain, naturally occurring ubiquitous human reovirus. In transformed cells with activated RAS pathway, this reovirus causes preferential lysis due to the inhibition of RNA-activated protein kinase (PKR) in these cells. In a phase-I dose escalation trial three of six patients with squamous cell cancer of the head and neck showed significant responses in combination with chemotherapy leading to the design of this phase-II study.
Methods: A single arm, open-label, phase-II study of REOLYSIN 3 X 1010 TCID50 given intravenously Days 1-5, with paclitaxel (175 mg/m2) and carboplatin (AUC 5) on Day-1 every three weeks was conducted in patients with platinum-refractory recurrent and/or metastatic squamous cell cancers of the oral cavity, larynx, or pharynx.
The primary end point was to determine the objective response rate (CR + PR) of the treatment regimen in the study population. Secondary objectives included the determination of disease control rate (CR + PR + SD) and the safety and tolerability of the treatment regimen. Patients were required to have measurable disease and evaluation of tumor status was conducted at baseline and every other cycle.
Results: Since September 2008, 14 patients age 29-61 (median 54) were enrolled and received a total of 57 cycles (range 1-10). Thirteen of 14 patients were ECOG performance status 0 or 1 and 1 was ECOG 2.
All patients were platinum-refractory and received other prior chemotherapy, radiotherapy, or combinations for their metastatic or recurrent disease. Ten of 14 patients received prior treatment with taxanes. Sites of disease included larynx (3), oral cavity (6), and pharynx (4), and other site (1).
Side effects were mild to moderate (Grade 1-2) including constitutional symptoms, fever, chills, and fatigue. Grade-3 toxicities included hypokalemia (2 patients), fatigue (1), nausea (1), and AST elevation (1). Hematological side effects included Gr-4 neutropenia in 1 patient, Gr-3 neutropenia in 5 patients, and Gr-3 anemia in 3 patients.
Thirteen patients were evaluable for response. Four partial responses were seen for an objective response rate of 31%.
Two patients had SD for =12 weeks for a disease control rate of 46%.
Two of the 4 patients with PR and both patients with SD had received prior treatment with taxanes.
Conclusion: REOLYSIN in combination with paclitaxel and carboplatin showed significant activity in patients with platinum-refractory head and neck cancer. An international, randomized, double-blind Phase-III trial of the combination for this target population is under way.
Pancreatic Gemc Combo Abstract Released at AACR
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=dbdc0b09-936f-4d6a-9c0a-756e0cd55f51&cKey=e39c6e23-bc11-43d2-8d42-e12eef71f226&mKey=%7bA57FF86D-D414-4079-BCBD-157746574F37%7d
Abstract Number: B55
Presentation Title:
A Study of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma
Location: West Hall, Level One, Moscone Center West
Poster Board Number: B55
Author Block:
Monica M. Mita1, Yubao Wang2, John Sarantopoulos1, Sushma Vemulapalli1, Benjamin George3, Alain Mita1, Mattew Coffey4, George Gill5, Devaligam Mahaligam1. 1Cancer Therapy and Research Center at UTHSCSA, San Antonio, TX; 2Cancer Therapy and Reserach Center, San Antonio, TX; 3Brooke Army Medical Center, San Antonio, TX; 4Oncolytics Biothech, Calgary, AB, Canada; 5Oncolytics Biotech, Calgary, AB, Canada
Abstract Body: Background: Pancreatic cancer (Pca) continues to have a dismal prognosis and very little progress has been made in finding new efficacious treatments. Oncolytic viruses have demonstrated cytotoxic effect in several tumor xenografts, particularly in cells with RAS pathway activation. REOLYSIN (Reovirus serotype 3) has shown extensive antitumor activity in preclinical models, as well as synergistic activity with cytotoxics including gemcitabine in various cancers. Several phase 1 and 2 clinical trials demonstrated tolerability and promising activity of REOLYSIN administered as a single agent in patients with solid tumors. Due to the high frequency of Kras pathway activation in Pca, we hypothesized that REOLYSIN may enhance the anticancer activity of chemotherapy in this tumor type. Therefore, this study was initiated to test the safety and efficacy of a combination of REOLYSIN with gemcitabine in previously untreated patients with Pca.
Methods: Patients with diagnosis of chemotherapy-naïve, surgically unresectable or metastatic Pca are eligible for the study. The primary objective is Clinical Benefit Rate (CBR=CR+PR+SD>12 weeks).
Secondary objectives include progression-free survival (PFS), toxicity, tolerability as well as pharmacokinetics (PK) and pharmacodynamics (PD). Patients are treated with gemcitabine at 800 mg/m2 day 1 and 8, and REOLYSIN administered IV at day 1, 2 and 8, 9. Tumor assessment is performed every 2 cycles (6 weeks). A two stage design is used for this study. In stage 1 at least 3/17 patients must achieve CBR in order to proceed to stage 2.
Results: Fourteen patients were enrolled in the study and 10 are evaluable for efficacy. Age ranged from 48 to 82 years, mean 67 years. All patients except one reported symptomatic improvement. No CR were reported.
Two patients have SD for =36 weeks and one patient continues on study with SD at 39 weeks.
An additional patient had an unconfirmed PR of less than 6 weeks.
Six patients had SD = 12 weeks.
The treatment was well tolerated with common non-hematological toxicities including grade 1 fever, chills, nausea and vomiting. Only two patients had grade 3 neutropenia lasting 1-2 days. No other grade 3 toxicities were seen.
Conclusion: The endpoint for the first stage of the study (=3 CBR in the first 17 patients) has been reached and therefore enrollment will continue. REOLYSIN in combination with gemcitabine has demonstrated clinical benefit in patients with unresectable Pca with a tolerable toxicity profile.
Current Investor Presentation - Updated Oct 2011
http://www.oncolyticsbiotech.com/pdf/OncolyticsOverview2011-bt6-Oct.pdf
EORTC Abstracts Listed - Panc and PhII H&N
Abstracts are now available online
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=dbdc0b09-936f-4d6a-9c0a-756e0cd55f51&cKey=e39c6e23-bc11-43d2-8d42-e12eef71f226&mKey={A57FF86D-D414-4079-BCBD-157746574F37}
B55 - A Study of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma
Monica M. Mita1, Yubao Wang2, John Sarantopoulos1, Sushma Vemulapalli1, Benjamin George3, Alain Mita1, Mattew Coffey4, George Gill5, Devaligam Mahaligam1. 1Cancer Therapy and Research Center at UTHSCSA, San Antonio, TX; 2Cancer Therapy and Reserach Center, San Antonio, TX; 3Brooke Army Medical Center, San Antonio, TX; 4Oncolytics Biothech, Calgary, AB, Canada; 5Oncolytics Biotech, Calgary, AB,
Canada Poster Session
PO.18. Clinical Trials 2
Mon, Nov 14, 12:30 - 2:30 PM
Also US Phase II H&N at
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=3689430c-4df3-4d0e-a34c-692c209b1f10&cKey=da6a20b4-0498-4900-9466-057b7e45c07d&mKey={A57FF86D-D414-4079-BCBD-157746574F37}
Presentation Abstract
C22
A phase II study of intravenous wild-type reovirus (Reolysin®) in combination with paclitaxel plus carboplatin in patients with platinum refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck
West Hall, Level One, Moscone Center West
Poster Board Number: C22
Anand B. Karnad1, Missak Haigentz2, Tracy Miley1, Matt Coffey3, George Gill3, Monica Mita1. 1CTRC, UT Health Science Center, San Antonio, TX; 2Montefiore Medical Center, Bronx, NY; 3Oncolytics Biotech Inc., Calgary, AB, Canada
Dr. Kevin Harrington - Interview Oncolytic Virotherapy
Thanks to moonthruclouds for the post
Interviewed by Nick Lemoine, Editor of Gene Therapy (Nature Specialist Journals) at he ESGCT & BSGT Conference in Brighton in October 2011, Dr Kevin Harrington talks about the progress made in oncolytic virotherapy for cancer. He highlights the advances made in the UK, and about the regulatory framework that supports work in this area.
Oncolytics at JMP Securities Healthcare Conference Sept28th
http://www.newswire.ca/en/releases/archive/September2011/22/c5620.html
Media Advisory - Oncolytics Biotech® Inc. to Present at the JMP Securities Healthcare Conference
CALGARY, Sept. 22, 2011 /CNW/ - Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX: ONC) (NASDAQ: ONCY), will present a corporate overview of the Company at the JMP Securities Healthcare Conference on Wednesday, September 28th, 2011 at 12:30 p.m. ET. The conference will take place on September 27th and 28th at the St. Regis New York Hotel in New York, NY.
A live audio link to the webcast presentation will be available at: http://wsw.com/webcast/jmp14/oncy/ or on the company's website at www.oncolyticsbiotech.com. It is recommended that listeners log on 10 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Dr. Patrick Lee- Oncolytic Viruses:Methods and Protocols
This work appears to identify details on viral replication in Ras active cells, and identifies the possibility of enhanced viral replication through exploitation of the (now identified) mechanisms.
Publication date is Nov 28, 2011, but a PDF can be downloaded now by Springer members.
Link: http://www.springerprotocols.com/Abstract/doi/10.1007/978-1-61779-340-0_12
Thanks rjc
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Exploring Host Factors that Impact Reovirus Replication, Dissemination, and Reovirus-Induced Cell Death in Cancer Versus Normal Cells in Culture
By: Maya Shmulevitz1, Patrick W. K. Lee2
Abstract
Oncolytic viruses, such as reovirus, offer a promising approach to cancer treatment. Concurrently, oncolytic viruses provide a valuable tool for deciphering unique attributes of cancer cells that support superior virus replication, cell death, or virus dissemination. Through our studies on various cancer cell lines, as well as isogenic cells with and without transformation by oncogenic Ras, we have identified at least four steps of virus replication that can be augmented in transformed cells. Ras transformation can support efficient reovirus uncoating during entry, production of progeny with high infectious capacity, and reovirus-induced apoptosis. Furthermore, Ras transformation also precludes interferon production following reovirus infection, permitting enhanced cell-to-cell virus spread. Methods that measure the efficiency of reovirus replication and dissemination described in this chapter can be used in combination with assorted cell culture systems to better understand the host factors that regulate reovirus oncolysis.
Affiliation(s): (1) Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
(2) Department of Pathology and Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada
Book Title: Oncolytic Viruses : Methods and Protocols
Series: Methods in Molecular Biology | Volume: 797 | Pub. Date: Nov-28-2011 | Page Range: 163-176 | DOI: 10.1007/978-1-61779-340-0_12
Subject: Infectious Diseases
Key Words: Oncolytic virus - Reovirus - Plaque titration - Immunohistochemistry -Apoptosis - Cell-to-cell spread - MAPK/ERK - Ras
Article in Chem/Eng News - Healing Viruses
Thanks for pointing this out RJC
Researchers take cancer-fighting viruses from bench to bedside
Aaron Rowe
http://pubs.acs.org/cen/science/89/8936sci2.html
More than 100 years ago, doctors noticed that some viruses have a remarkable ability to kill cancer cells while leaving healthy tissue almost unharmed. Since then, researchers have been trying to develop such viruses as treatments for cancer, but it’s only in recent years that their century of effort has begun to bear fruit. Now, a dozen oncolytic viruses are being tested in the clinic, with a couple poised to gain Food & Drug Administration approval in the next two years.
That brimming pipeline has many scientists in the field feeling confident. Most viral cancer agents in development have been shown to be safe and fairly effective, says Matt Coffey, cofounder of Oncolytics Biotech, one of three companies with cancer-killing viruses in Phase III human trials.
Until recently, it was widely believed that oncolytic viruses exerted their anticancer effects solely by replicating within malignant cells and then destroying them. But several studies have called that viewpoint into question, and at least one additional factor now seems to be at play, explains Richard G. Vile, an immunologist at the Mayo Clinic. In addition to killing cancer cells by replicating within them, the viruses provoke the immune system to more aggressively recognize and fight cancer. In other words, the oncolytic virus also works like a cancer vaccine, Vile explains.
“I think ultimately the strategy is going to be to use the virus infection to reduce the tumor burden—sort of a biologic surgery, initially,” says Timothy Cripe, an oncologist at Cincinnati Children’s Hospital Medical Center, where four oncolytic virus trials are taking place. Later in a course of treatment, he says, doctors may also use the viruses “to sensitize the immune response to keep the tumors from growing back.”
In recent studies, oncolytic viruses have shown substantial signs of efficacy. The results are good enough that Amgen recently acquired BioVex and its Phase III oncolytic virus candidate ( C&EN, Jan. 31, page 8). “If we do achieve the kind of clinical results that we are hoping for, it really will have a major effect on the field of oncology,” says Joe Miletich, Amgen’s senior vice president of R&D.
Many early victories in the field of oncolytic viruses were brought about by localized injections directly into tumors. Those localized doses are quite small compared with the systemic treatments that are being tested today. Only recently has it become viable to administer long courses and long doses of viruses systemically. That’s because producing enough of the viruses to conduct large, systemic trials is challenging.
Coffey notes that Oncolytics Biotech turned to Sigma-Aldrich for help in preparing enormous quantities of virus that can be given alongside traditional chemotherapy. He says Sigma-Aldrich took a huge risk when it got into the virus production game but that the gamble has paid off for the company. The chemical firm acquired a massive production facility that has made his company’s large clinical trials of oncolytic virus agents possible.
“With improved production techniques, we’re seeing the field grow much more rapidly just because you can suddenly entertain larger studies,” Coffey says. “You can mass-produce these now, which had been a challenge for some of these modified vectors before.”
However, several problems continue to limit the effectiveness of oncolytic viruses. For one, diagnostics that could be used to select the right virus for a patient are still at a very early academic stage, so doctors currently have no way to predict whether particular viruses will be effective for their patients. For example, JX-594, a modified vaccinia virus developed by Jennerex Biotherapeutics recently showed impressive efficacy in some cancer patients, but those results were not consistent, explains Evanthia Galanis, an oncologist at the Mayo Clinic (Nature, DOI: 10.1038/nature10358).
Molecular tests that check for cancer cell types could help. For instance, Reolysin, a particularly innocuous virus developed by Oncolytics Biotech, prefers to replicate in cancer cells with an active Ras signaling pathway. Cells that have active Ras don’t produce a defensive protein called PKR, and that leaves them vulnerable to viral attack.
Empirical tests for viral replication within a patient’s cancer cells might also help. Several teams have explored adding markers to viruses and then administering the combination simultaneously at a low dose. A virus that enters cancer cells could then be identified by its marker.
Scientists are also trying to optimize cell delivery of viruses. Some have modified viruses with peptides that help them invade tumor cells. Others have found that the precise timing of a virus injection matters—that there is a window after standard chemotherapy drugs have been administered when virus will have stronger ef?fects.
Researchers are also looking into using stem cells as viral delivery vehicles. In theory, this could allow constant, long-term delivery of viral particles. The first human trial of a treatment that uses stem cells as virus carriers could begin within a year, according to Galanis.
In addition, researchers will need to develop new ways to make sure viruses destroy metastases, which ultimately are what usually kill patients, Cripe says.
A key problem in administering oncolytic viruses is that they have a hard time getting through the thick layers of extracellular matrix that often surround tumors. Some researchers have tried to modify viruses to increase their chances of surmounting this barrier. One strategy is to add proteases to the surface of each virus, Coffey says.
And although oncolytic viruses can be highly selective for cancer cells, some tend to accumulate in the liver when they are administered systemically. To reduce the risk of liver damage from the expression of viral genes in noncancerous liver cells, several teams have started inserting gene-silencing microRNA sequences into the viruses (Nat. Biotechnol., DOI: 10.1038/nbt1208-1346). This is like creating a “tear here” perforation in the virus: If it enters a liver cell, it’s toast.
If oncolytic viruses make it to cancer patients’ bedsides, it’s likely the viruses will do it in combination with traditional cancer drugs. There seems to be a great deal of synergy between the two, Coffey says. Drugs such as carboplatin and paclitaxel stabilize sites where viruses bind to host proteins, allowing the viruses to replicate more easily.
To further enhance the synergy of drug-virus combinations, many groups have begun adding drug- or radiation-sensitizing genes to oncolytic viruses. Adding genes that give viruses greater cell-penetrating ability could also be helpful, Coffey says. “There has been a lot of academic work in viruses to sort of mix and match and get the benefits of everything that you possibly can in one vector,” he says.
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society
Oncolytics to Present at Wedbush 2011 Life Sciences Management Access Conference on August 16, 2011 at 8:35AM EDT
http://www.integratir.com/newsrelease.asp?news=2131025372&ticker=T.ONC&lang=EN&ny=on
CALGARY, AB, August 11, 2011 --- Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX: ONC, NASDAQ: ONCY), will present a corporate overview of the Company at the Wedbush 2011 Life Sciences Management Access Conference on Tuesday, August 16th, 2011 at 8:35 a.m. ET. The conference will take place from August 16th to 17th at the Le Parker Meridien Hotel in New York, NY.
A live audio link to the webcast presentation will be available at: http://wsw.com/webcast/wedbush17/oncy/ , or on the company’s website at www.oncolyticsbiotech.com. It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Oncolytics Current Investor Presentation
http://www.oncolyticsbiotech.com/pdf/ONCY_Investor_Presentation_July18-2011.pdf
Highlights from the Cannacord conference along with the current presentation. Thanks taltell, I added a few to your list.
Neil Marucca of Cannacord on introduction -Oncolytics is developing the "Most compelling oncolytic virus in our view"
PHIII H&N - Awaiting for approval to proceed from 6 more countries 80 to 90 centers enrolling in qtr 4. On track to finish enrollment of first 80 patients in QTR 4. Currently approved to be trialed in 6 countries, US, UK, Belgium, Canada, France and Hungary.
Adaptive trial design allows for PFS looks at several points during the study after the first interim 80 patients with an expected total enrollment of just under 200 patients. With 80 or 90 centers expected to be enrolling by years end this trial will only have to enroll an average of under three patients per center to complete enrollment of 200.
Ovarian trial - enrollment on track with randomized Ovarian - 120 patient 2 arm study. Enrollment should end by end of qtr 1 2012.
Panc trials - BT spoke about importance of KRAS status in Panc. Seeing almost absolute correlation between KRAS status and clinical outcome of stable disease in Gemz/panc trial. Randomized Carb/Tax/Reo - 5 centers by September - looking at absolute responses and PFS - quite hopeful about this trial.
NSLC and Squamous LC trials - nothing much new. NSCLC investigator (Villalona) still wants a randomized trial. But new randomized trial will be either squamous or NSCLC.
Colorectal with Folfuri trial - finishing off Ph I study - expectations are high for this trial because of the KRAS activation.
Over 500 patients now treated with no DLT (over 100 by NCI trials, over 400 by Onc trials).
Cost of manufacturing will be 1.5% of the final price and could go under that if they scale up the batches. They have enough on the shelf already to treat 10's of thousands. Some of it will probably age out before approval but very comforting to know supply will be there for kickoff.
The current contract manufacturing facility owned and run by Sigma Aldridge in Carlsbad Ca is producing Reolysin. One other client using this facility is TEVA.
See
http://www.molecularmed.com/ - 100 Liter Bioreactors and Vial filling capacity of up to 10,000 units per day. (Fill capacity of 3.6 Million per year) Everyting ONCY needs here for initial small scale production in one facility. SAFC also runs facilities in Ireland, the UK, Switzerland, Madison Wi, St Louis, Wuxi, China and Bangalore India.
http://www.safcglobal.com/etc/medialib/docs/SAFC/General_Information/carlsbad_facility.Par.0001.File.tmp/carlsbad_facility.pdf
for more info on this facility.
Expectation are that there will be two more randomized trials announced by the end of 2011. One in Colorectal and one in either NSCLC or SCCLC. Evaluation of the SCCLC trial and decision by year end suggests that this trial will be completed in Q4 of this year.
Reports that responses in metastatic cancer in the Liver and Lungs happen regardless of whether a primary response has been observed in many patients.
Approval hopefully in a couple of years.
He did not talk about the Children Oncology Group trial, or the Glioma trial however I did hear that the US Phase II H&N trial results will be released in the near future.
Latest Financial factoids
Shares Outstanding (May 11, 2011) 71,209,318
Warrants Expiring Price
Nov 8, 2012 $6.15 1,794,750
Nov 8, 2012 $4.60 375,360
Options $4.57 (average) 4,604,094
Fully Diluted shares outstanding (May 11, 2011) 77,983,522
Est. Cash/Cash Equivalents $53.5 M
Current as of (March 31, 2011)
Here is the link to the archived Webcast.
http://wsw.com/webcast/canaccord4/oncy/
Brennan's cancer battle inspires staff
http://www.thisweeknews.com/live/content/bexley/stories/2011/07/20/brennans-cancer-battle-inspires-staff.html?sid=104
A touching story of a Stage IV patient in the NCI sponsored Phase II Reolysin+CarboTax Pancreatic trial.
Brennan's cancer battle inspires staff
Wednesday, July 20, 2011 08:42 AM
By JEFF DONAHUE
ThisWeek Community Newspapers
When Bexley Mayor John Brennan announced in February that he had been diagnosed with pancreatic cancer, a pall fell over city council chambers.
"I'm going to fight this," he said at the time. "I'm going to get through this."
Brennan has lived up to his word.
After enrolling in an aggressive, experimental treatment program at the James Cancer Center at the Ohio State University Medical Center, Brennan struggled, losing more than 30 pounds and most of his hair due to the intensity of his treatment regimen.
A familiar face at virtually every community event and city meeting, he had to curtail both his business and social schedule to deal with his sudden loss of energy. Those closest to him feared the worst.
"Although the outlook upon learning of the news of his cancer seemed poor, this is not the situation now," Bexley city attorney Lou Chodosh said. "John has been undergoing treatment that has been working. He stated early on he was going to fight this, and he has done so.
"John asked his doctor whether he could run for mayor again, and the doctor's response was, 'Why not?' The tumors have shrunk, and he has been told they will continue to do so.
"His optimism is contagious. I meet with the mayor regularly to keep him up to date with legal issues, new ordinances, and resident issues that have come to my attention. Over the last six weeks, he has gotten stronger, and continues to do so, Chodosh said.
"Everywhere I go in Bexley someone tells me to wish John well, and to tell him he is an inspiration," he said.
Over the Fourth of July weekend, Brennan said, he visited 19 block parties and still had the energy to take part in all of the city-sponsored holiday events.
"It's been great to see John's energy picking up and his spirits increasing over the past few months," Chodosh said.
"His turnaround has been remarkable and his tenacity and determination are impressive."
City council member Ben Kessler said he has been struck by Brennan's dedication.
"City council and the city directors have rallied behind John and helped him as he's needed it, but despite being in aggressive treatment, he's been staying on top of city business and fulfilling his duties admirably," Kessler said. "With his energy up and his scans showing positive signs of recovery, I'm looking forward to many more years of John's friendship and leadership."
City council member Jed Morison agreed.
"John and his family have been remarkable throughout this entire time," he said. "He sets a great example for all of us and proves that a positive attitude has great healing power. We are so happy he is doing well."
City council member Mark Masser said he sees no reason why Brennan shouldn't run for re-election in November.
"John is undergoing treatment for his cancer and has been given encouraging reports from his doctor," Masser said. "He is fulfilling his duties as mayor now, and I am confident that he will continue to do so if he is re-elected."
Brennan said he is one of a select group of patients in the United States involved in a clinical trial for the drug Reolysin, discovered in Calgary in 2005 and tested in England in 2008.
Reolysin is currently being evaluated in phase II clinical trials for treating melanoma, pancreatic, lung, ovarian, and colorectal cancers and in a phase III trial in head and neck cancer. Clinical trials have demonstrated that Reolysin may have activity across a variety of cancer types when administered alone and in combination with other cancer therapies.
"If it gets into Phase III, they could probably make it available with the results they are having," Brennan said. "I would invest money in it. It has actually shrunk my pancreatic tumor and the liver tumor somewhat and a couple of little spots I had are gone."
Part of his therapy involves the injection of a living flu virus that attacks the cancerous cells. Unfortunately, that means with each treatment, he has to endure the symptoms of the flu, including chills and fever.
"But, I know now that every Tuesday, I'm going to have that reaction and you fight through it," he said.
Brennan said there has been much more than just medicine involved in his comeback.
"The nurses at The James have all been great," he said. "The volunteers, the doctors, everyone is just wonderful. It's just uplifting.
"It's a great place," he said. "I'd like to do a public service announcement for them. Anybody who has any kind of cancer that's severe, that's where they need to be. We're really lucky to have it here."
Brennan said his doctor gave him the OK to run for re-election in November.
"He told me there is no reason I shouldn't be even better in August and September," Brennan said. "He said, 'There's no reason you can't throw your hat in the ring and run.' So, I've been circulating my petitions and I'll be turning those in in a week or so."
Brennan said this will be his last run for the mayor's office.
"Hopefully, I'll get re-elected," he said. "I just want to do four more years. I won't go beyond that. I think eight years would be plenty. Who knows what will happen in the future, but I'm assuming I'm going to get good results. The doctor said there may even be some form of remission in the next year."
Brennan said a positive attitude has been vital to his recovery.
"Ninety percent of it's having a sense of humor and being optimistic," he said. "A lot of people just don't want to do the chemo and give up. Anybody can get through it if you put your mind to it.
"People told me to meditate and read cantor books. What I do is tape Letterman and Jimmy Fallon or Comedy Central and watch those when I need a laugh. I try and stay real upbeat. I've had very few low days."
Debbie Maynard, Brennan's assistant at City Hall, shakes her head in wonder when asked about Brennan's comeback.
"It's just a miracle," she said. "What a blessing."
An older story appears below, apparently he started in the last week in Feb 2011 so he has been enrolled for almost 5 months.
Bexley mayor announces cancer diagnosis, Re-Election bid
http://www.thisweeknews.com/live/content/bexley/stories/2011/07/20/brennans-cancer-battle-inspires-staff.html?sid=104
Wednesday, February 23, 2011 10:25 AM
By JEFF DONAHUE
ThisWeek Community Newspapers
Bexley Mayor John Brennan announced Tuesday, Feb. 22, that he will be fighting two battles this year -- and intends to win them both.
Brennan told Bexley City Council that he has been diagnosed with cancer and that he will seek a second term in office in November.
"Last week I had gallbladder surgery and during the surgery, they found some cancer in my body," Brennan said. "I'll be starting treatment next week. I had a scan today. I'll get the results tomorrow. I'm going to The James (Cancer Center) on Monday to consult with a doctor there and probably within a week or so, I'll be starting my first treatments."
Brennan said the diagnosis led him to move up the announcement that he will seek re-election in November.
"I was going to announce at the State of the City on March 15 that I am seeking a second term as mayor, but instead of waiting that long, I'd like to announce that tonight," he said. "I'm going to fight this. I'm going to get through this.
"I appreciate everybody's prayers and support," Brennan said. "This has been an eye-opening experience. There are so many good people here in this community. It's just amazing."
Brennan said he has been doing some work from home and has been putting in a couple of hours a day this week at City Hall.
Council President Jeff McClelland said the community is behind Brennan in his battle against cancer.
"I know that I, as well as all the council members, have been bombarded with questions about how the mayor is doing and it's because people care so much," McClelland said. "You know that you have our full and complete support, collectively and individually.
"This is great news to hear you announce your candidacy for a second term," McClelland added. "You're going to fight this thing. We will support you in your fight and we're going to beat this thing."
Positive Interim Trial Results Presented in Amsterdam
http://finance.yahoo.com/news/Oncolytics-Biotech-Inc-prnews-300044770.html?x=0&.v=33
Selected for a Mini Oral Presentation from 1500 abstracts submitted and 400 accepted at the World Lung Cancer Conference. Detailed patient by patient results included showing EGFR/KRAS status and TTP.
CALGARY, July 6, 2011 /PRNewswire/ - Oncolytics Biotech Inc. (TSX:ONC.to - News) ("Oncolytics") today announced that a presentation covering interim preliminary results from a Phase 2 clinical trial using intravenous administration of REOLYSIN® in combination with paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC) with Kras or EGFR-activated tumours was made today at the International Association for the Study of Lung Cancer World Conference on Lung Cancer. The conference is being held in Amsterdam, the Netherlands from July 3rd - 7th 2011.
The presentation, entitled "Phase II study of reovirus with paclitaxel (P) and carboplatin (C) in patients with metastatic non-small cell lung cancer (NSCLC) who have Kras or EGFR-activated tumors", was given by Dr. Miguel Villalona-Calero, principal investigator for the study, and indicated that 22 patients had received Reovirus (REOLYSIN) (3 x 1010 TCID50) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Initial doses used were carboplatin AUC 6 on day one, and palitaxel 200 mg/m2, on day one of each 21-day cycle. Due to exacerbation of prior gastrointestinal conditions and febrile neutropenia (one each) in the first two patients, doses were reduced to paclitaxel 175 mg/m2 and carboplatin AUC 5.
To date the study has enrolled patients with Adenocarcinoma (15), Squamous Cell Carcinoma (three), Bronchioloalveolar Carcinoma (one), and not otherwise specified non-small cell lung cancer (three). Molecular tumor demographics included: nine Kras mutant, three EGFR mutant, 16 EGFR amplified. Response evaluation to date in 21 patients showed six partial responses (PR) (28.6%), 13 stable disease (SD) (61.9%), two progressive disease (PD) (9.5%). This translates into a clinical benefit rate (complete response (CR)+PR+SD) of 90.5% and a response rate (CR+PR) of 28.6%. The investigators noted that the clinical benefit noted so far is encouraging and that a follow up randomized clinical trial appears warranted.
"The patient response and clinical benefit rates observed in this trial are very encouraging. We will decide which lung cancer indication will proceed into a randomized clinical study based on this data and the data we expect from our ongoing Phase II trial in squamous cell carcinoma lung cancer," said Dr. Brad Thompson, President and CEO of Oncolytics.
The full presentation is available on the Company's website at www.oncolyticsbiotech.com.
Conference Call Details
Dr. Brad Thompson, President and CEO of Oncolytics, will host a conference call and webcast on Wednesday, July 6th, 2011 at 6:30 a.m. MT (8:30 a.m. ET) to discuss in more depth the presentation covering the Phase II NSCLC data. To access the conference call by telephone, dial 1-647-427-7450 or 1-888-231-8191. A live audio webcast will also be available at the following link: http://www.newswire.ca/en/webcast/viewEvent.cgi?eventID=3563560 or through the Company's website at www.oncolyticsbiotech.com. Please connect at least 15 minutes prior to the webcast to ensure adequate time for any software download that may be needed. A replay of the webcast will be available at www.oncolyticsbiotech.com and will also be available by telephone through July 13th, 2011. To access the telephone replay, dial 1-416-849-0833 or 1-800-642-1687 and enter reservation number 78454074 followed by the number sign.
Link to the slide show at
http://media.integratir.com/T.ONC/ppt/Dr%20%20V%20Reo%20IASLC.pdf
Interim Conclusions based on 21 evaluatable patients:
- Patient selection based on molecular profile for first line therapy in NSCLC is feasible.
- Reovirus can be administered safety in combination with C/P
- Clinical benefit observed so far is encouraging (90+% in Stage 4 patients)
- Historical controls are not informative on the effect of chemotherapy in Kras activated NSCLC
- A randomized trial to differentiate the contribution of the reovirus to the chemotherapy appears warranted.
Background on Dr. Miguel A. Villalona-Calero M.D.
Holds the Dorothy M. Davis Chair in Cancer Research at Ohio State University
http://medicalcenter.osu.edu/mediaroom/discovery/archive/2010/10/22/latest-news-on-endowed-chairs-and-professorships-2.aspx
Dr. Miguel Villalona-Calero is an internationally recognized expert in experimental therapeutics and lung cancer. He directs Ohio State’s Solid Tumor Experimental Therapeutics program. He also is director of the new Division of Medical Oncology, which will be instrumental in the growth of the cancer program at Ohio State. He is a National Cancer Institute-funded scholar and a member of its Investigational Drug Steering Committee. He has also been involved in several significant national scientific committees for the American Society for Clinical Oncology, the American Association for Cancer Research and the National Cancer Institute.
Namesake: Dorothy and William Davis were lifelong supporters of The Ohio State University. In 1987, Dorothy established The Dorothy M. Davis Chair in Cancer Research to support a scientist with significant achievements in cancer research at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute. Davis was vitally interested in the future of the University, medical research and higher education.
Also much much more at:
https://pro.osu.edu/profiles/villalona.1/
A455A Starling Loving Hall
320 W 10th Ave
Columbus, OH 43210
Phone: (614) 366-5068
Fax: (614) 293-7520
Email: miguel.villalona@osumc.edu
URL: http://internalmedicine.osu.edu/hemonc/879.cfm
Current OSU Appointments
Professor, Medical Oncology
Professor, Pharmacology
Abstracts and Short Entries
Villalona-Calero M, Lam E, Otterson G, Zhao W, Donthireddy K, Thurmond J, Hade E, Pennington J, Mettinger K, Coffey M. 2011. Phase II Study of Reovirus with Paclitaxel (P) and Carboplatin (C) in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Kras or EGFR-Activated Tumors [Abstract]. Proceedings of the 14th World Conference on Lung Cancer: Journal of Thoracic Oncology. (July) [Peer Reviewed] (Formally Accepted)
Dr.Morris Poster for Preclinincal research released for WLCC
Session Info: Poster Session, [P2] Poster Session 2
Day/Date: Tuesday, July 5, 2011
Session Time: 12:15 PM - 2:00 PM
Room: Exhibition Hall
P2.033 | Evidence of Significant Efficacy of the Oncolytic Virus, Reovirus, for the Treatment of Lung Cancer
A. Kellar, N. Ronaghan*, Z.Q. Shi, C. Thirukkumaran, D. Morris
University of Calgary/CANADA
Background:
Lung cancer is the leading cause of cancer mortality worldwide. It is estimated that approximately 1,529,560 people were diagnosed with cancer in 2010, resulting in approximately 569,490 deaths. Surgical resection and aggressive chemotherapies prove to be only marginally effective as five-year survival ranges from 13% in men and 17% in women. Reovirus (RV), a double-stranded RNA virus, has been shown to be effective against a myriad of cancers through its ability to preferentially lyse cancer cells with aberrant Ras or other pathway signaling. In this study, we investigate the potential of RV (serotype 3, strain Dearing) as a novel treatment for both non-small cell and small-cell lung cancer in vitro and in vivo.
Methods:
RV-induced cytotoxicity was assessed by WST-1 viability assays for both NSCLC cell lines: (A549, H460, H1299, HCC4006, H1975, H226, HCC827, HCC2935) and SCLC cell lines: (DMS-53, and H69) in vitro. RV and chemotherapy combination studies were conducted for the DMS-53, H69, HCC827 and H226 cell lines, evaluating the cytotoxic effects of reovirus in combination with each of the following: cisplatin, pemetrexed, etoposide, and erlotinib using the constant-ratio design and combination index method of Chou Talalay. In order to further evaluate the potential of RV as novel therapeutic for lung cancer, three xenograft models (H460, H1299 and DMS-53) were utilized to test RV-induced cytotoxicity alone and in combination with chemotherapy in vivo.
Results:
RV induces cytotoxic effects at a multiplicity of infection (MOI) of 40 within 48h for both NSCLC cell lines: (A549, H460, H1299, HCC4006, H1975, H226, HCC827, HCC2935) and SCLC cell lines: (DMS-53, and H69) in vitro. These findings are particularly unique for SCLC, in that effective therapies are limited. Interestingly, preliminary data also suggests that RV in combination with chemotherapy has potentially synergistic cytotoxic effects in vitro. In addition, current xenograft data indicates that both the H460 and H1299 cell lines are intrinsically sensitive to RV in vivo. Updated results will be presented.
Conclusion:
These preclinical results suggest that RV holds promise as a novel therapeutic for both non-small cell and small cell lung cancer and that it warrants further investigation in clinical trials. There is currently a phase III (Typo should be Phase II) clinical trial for RV in combination with carboplatin for the treatment of NSCLC. These results may suggest that other combinations should be examined and that RV may have the potential to revolutionize therapy for SCLC.
Reovirus Research -14th World Conference on Lung Cancer
http://ih.advfn.com/p.php?pid=nmona&article=47991934&symbol=ONCY
Oncolytics Biotech Inc. (TSX:ONC), (NASDAQ:ONCY) ("Oncolytics") today announced that an abstract covering interim preliminary results from a Phase 2 clinical trial using intravenous administration of REOLYSIN® in combination with paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC) with Kras or EGFR-activated tumours is available on the International Association for the Study of Lung Cancer World Conference on Lung Cancer website at http://www.2011worldlungcancer.org/index.html. The conference is being held in Amsterdam, the Netherlands from July 3rd - 7th 2011.
The abstract, entitled "Phase II study of reovirus with paclitaxel (P) and carboplatin (C) in patients with metastatic non-small cell lung cancer (NSCLC) who have Kras or EGFR-activated tumors", authored by Villalona-Calero et al, indicated that as of the date of submission of the abstract 21 patients had received Reovirus (REOLYSIN) (3 x 1010 TCID50) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Initial doses used were carboplatin AUC 6 on day one, and palitaxel 200 mg/m2, on day one of each 21-day cycle. Due to exacerbation of prior gastrointestinal conditions and febrile neutropenia (one each) in first two patients, doses were reduced to paclitaxel 175 mg/m m2 and carboplatin AUC 5. Overall, 85 cycles (per patient median four, range one to eight) were administered. Grade 3-4 adverse events included grade 4 neutropenia (four patients), anemia, fatigue, electrolyte abnormalities, diarrhea, (two patients), and single cases of nausea, vomiting, and sepsis. Molecular tumor demographics included: eight Kras mutant, three EGFR mutant, 15 EGFR amplified. Response evaluation to date in 20 patients showed six partial responses (PR) (30%), 12 stable disease (SD)(60%), two progressive disease (PD)(10%). This translates into a clinical benefit rate (complete response (CR)+PR+SD) of 90% and a response rate (CR+PR) of 30%.
"Although preliminary, this data is very encouraging. Once we have data from our ongoing Phase II trial in squamous cell carcinoma lung cancer, we will decide which lung cancer indication will proceed into a randomized clinical study," said Dr. Brad Thompson, President and CEO of Oncolytics.
SOURCE Oncolytics Biotech Inc.
ONCY 2011 AGM Transcript - May 2011
Thanks to lordlucansalive on Yahoo V2 for doing the transcript
PRESENTATION
Thank you all for coming along today, we greatly appreciate it. We really appreciate your support
and ongoing kind of dialogue that we have with many of you on an ongoing basis. What we’d like
today is to talk about Oncolytics in a somewhat different light than is normally our wont at the
annual meeting and take a more slightly historical approach to try to tie together where we’ve been,
what we’ve achieved and where we are today, with respect to several key important areas of activity
inside the company.
The hope is that this will allow people to gain some perspective on some of the things that we’ve
done, that have led into our current activities, and kind of give you a sense of where the company is
flowing forward from this time today.
[Forward looking statements etc…]
So today I’ll be talking about 5 key areas:
I’ll be talking about our financial position first, talking about two very key areas that often don’t get
talked about, which is our intellectual property portfolio and our manufacturing programme. And
then move in to talking about some work we’re doing pre-clinically and have done pre-clinically and
how that flows into our clinical trial programme and where we’re planning on going from there.
After that I’ll make some minor conclusions and then entertain any questions you may have at that
point.
Biotechnology has come through an interesting (in the ancient curse mode) several years with
respect to financial transactions. And while things have actually improved I think markedly in the last
12-15 months we’re still faced with this situation where it’s a relatively selective financing
environment.
And so part of what Oncolytics I think has done over its history is to do whatever it needs to at the
appropriate time to raise the resources to support our programmes and so today we’ve actually
raised just under $182M but the complexion of that fund raising I think is a little different than what
people would expect.
Just under, or just over, half of that is what I would think of as old-fashioned traditional public
offerings you know, prospectus-driven public offering, and the offerings that people tend to see and
feel and sense.
But on top of all that, is a variety of textures of things. About a quarter of the money has been from
the exercise of options and warrants, attached to financings primarily. Most recently, our now
biggest shareholder exercised warrants that were barely in the money as a token or demonstration
of support for the company financially to allow us to do certain things. And it’s a very important
component, at least for Oncolytics, of the financing tool. As you go down this list you’ll see that
there’s a number of other types of transactions.
When we started the company it was mostly private placements, prior to us going public, and one
small VC round after going public, and then the innovative ones, which, candidly, while the numbers
are small are the ones that you do when things are really tough, that actually really make the
difference.
We owned a stake in Transition Therapeutics which is a Toronto based company here; Dr Tony Cruz
is the very able CEO of that company and our intent at the time was to actually take a long term
stake in that as we go forward looking at new products things were very difficult and we had the
opportunity to sell the shares which then catalysed 3 private placements 2 days after that. So it
wasn’t a huge amount of money at the start but it certainly catalysed a number of things .
We had some shares in another small Canadian company called BCY that we got rid of and most
recently last year at the start of the year when things were relatively dire we purchased a failed
company from Edmonton for the cash in the bank.
The net effect of that of course is to come up with this number, but I think these last financings
while rather small in size came at very critical junctures in the market when there were really no
other alternatives for raising money and helped catalyse the more normal course of funding.
And so I think our message is that Oncolytics does pretty much what it needs to do to raise capital in
the most appropriate way in the market at the time. And I think the fact that we’re here today after
the carnage of last year is a testimony to our ability to do that.
Looking at the intellectual property portfolio, people tend to really underestimate the value and the
requirement for an ongoing IP programme within companies like Oncolytics. At the end of the day,
assuming Reolysin works, we get the product registered, without a robust and multi-layered and
textured intellectual property portfolio, that has an asset value of pretty much zero. So all the work
that we do to get a product approved in the end of the day unless we have this on the front of that
really isn’t worth anything to us.
And so we’ve been in active operation now since the fall of 1999 so arguably 12 years and we’ve
spent an average of $3,000 a day for that 12 year period working on our IP portfolio and it’s our
intention going forward to continue and expand that effort.
I just wanted to show you some of the layering over the years, and this is not an exhaustive list by
any means. We just took some selective highlights and just US only. You can see, and I think this is
more of interest for people later when they can actually pick through this when this talk is posted on
our website.
To actually see that there’s a kind of a sequence of claims that get allowed, a sequence of key areas,
that was methodically sought after in our IP portfolio. And of course the goal is that on the day we
have product approval or that morning if we get approval in the afternoon I expect Mary Ann
[Dillahunty] and Matt [Coffey] to be still filing IP up until the 3 seconds before and that’s absolutely
critical because we want the broadest possible window going forward, with as many layers on that
window going forward, to help fend off the inevitable competition on what we hope is a successful
product.
This is an example, I mean our very first claims were the claims that Dr Matt Coffey and his
colleagues from when they were at the University of Calgary filed the original patents that were
rolled into Oncolytics and so very important claims about treating RAS, it’s the first time you see RAS
in our patent portfolios, RAS-mediated cancers, and things beyond cancers which are cell
proliferative diseases like neurofibromatosis, by administering Reo it’s an incredibly important start.
It’s a ‘treating this disease with this agent’ kind of claim.
And then you broaden that out. Mary Ann’s been directing this portfolio from its very start and has
done I think just an unbelievably super job at managing, which is a very long term and very layered
process.
Then you broaden out the treatment claims. You broaden it out to start looking at combination
therapies, with immunosuppressants, with other agents, with radiation, and it’s just a very
systematic approach to broadening out a patent portfolio. But again with the goal on the day of
product approval of having as broad a window as you can.
And so reassortments, you’re looking at transplantation first of all, then more biochemistry, and you
start getting into the things like purification methods, delivery methods, pharmaceutical
composition.
And finally, which was an interesting one for the stage of development we’re at, last year getting our
first pure composition of matter claims on our clinical isolate, which is a little late in the game to get
that, but thankfully it is because that takes us to 2028 on those claims.
Going forward, and this I think is a key slide. Right now we have over 250 issued patents, and that
number changes daily. Right now 41 are in the US, 11 in our home jurisdiction of Canada and
probably the most important part of this is the ongoing effort we continue to file, continue to
broaden out the IP base. But honestly in the end, this is where the value of this company is. At the
end of the day if this doesn’t have any structure to it then it really wasn’t worth doing. It’s just very
important to note that.
Manufacturing. And of course today we announced a very important step in that which I’ll allude to
at the end, that is also key. More filings at the FDA fail because of manufacturing concerns than they
do clinical trial concerns, clinical data concerns. Manufacturing is an absolutely critical component in
a biologics programme it can’t be overestimated how important focusing on this is.
I just wanted to compare where we started and where we are now. In 2000 when we first started
treating patients this is the process that we used to purify them and the details aren’t really that
important but it’s basically a lab-based process. It was one of these 15 litre flasks which are about
this big around – I can tote a 15 litre flask around – extract with some fairly nasty environmentally
unfriendly products and purify by a lab-based process which is centrifugation and you fill that and
you put it in human beings.
Certainly not a commercial process: it’s not commercial from a cost perspective, it’s not commercial
from a scale perspective, and it’s not commercial from an ‘I doubt the FDA would ever let you go to
product approval’ perspective. So it certainly allowed us to get into the clinic, but it did not allow you
to meet the 3 goals of a cost-effective, bulk manufacturing, approvable process.
Here we are today at 2011 – this is literally 11 years worth of work where we’re spending probably
between $7M and $9M a year, every year, on a very focused, methodical, process development, to
come up with a commercial scalable process. And this is what the process, I won’t go through it but
it’s a very different process, as you can see there’re some very unique steps in that which will roll
back into our IP portfolio that are unique to Reolysin and possibly useful in other areas. It’s really the
result of a great deal of work by a great deal of people and it’s absolutely important.
Now what you see when you look through the history of our process is this scalability issue. If you
take a look at the dosages that we produced at this equivalent to our standard IV dosage, over time
you see there’s the sequence going through different manufacturers, which is also an important
element, and different yields and different scales.
So we started out with a corporation in the States called BioReliance, that gave us clinical product,
got us into the clinic; not a registration process, not economical. Did our first scale-up work at
BioReliance, and then moving over to Cobra in the UK, and you can see the scale – you start getting a
30-fold yield improvement.
Then our first work at Sigma-Aldrich Fine Chemicals, who we’ve signed a commercial manufacturing
agreement with, announced this morning. Originally at the 40litre scale, again a scale improvement,
and then up into the 100litre scale where we are now. In our last runs we’ve certainly got upwards
of 100,000 dosages out of a single 100litre batch, which I can put my arms round – I can’t lift –
because it’s a little heavy.
And certainly what this does is it gives us economies of scale – this process is now economical. It
gives us a scale that’s at the bottom end of commercial. We can actually fix the process which we’ve
done for our Phase 3 study and ensure that the process is what we’re using for our final
confirmation runs and registration runs. And it acts as a huge asset with respect to us either talking
to corporate partners, because it’s very reassuring to them that we’re actually doing our
manufacturing at a quality place like Sigma-Aldrich. Sigma-Aldrich Fine Chemicals produces bulk
pharmaceutical grade material for virtually every big pharma and is highly regarded in our industry,
and it’s very reassuring to have somebody of that stability and stature doing this work for us.
And so that’s where we are today – we go from a lab-based process to a process that today has a
reputable manufacturer signing a commercial agreement to produce this product for us for our final
confirmation work and to start stockpiling product for hopefully eventual sale. Nice to say that,
finally.
So I think it just bears … again it was a 10 or 11 year process, so it has to be paid attention to, and I
have to I guess, must credit our key men and Matt Coffey who led that effort for taking care of that
over the last decade.
Now preclinical research. People often ask the question why we continue to do preclinical research.
And it’s our model in this business to actually do work not in humans first and then if we can do
some translational work in humans so they don’t have clinical endpoints, they’re more technical
endpoints, which I think of as preclinical because they don’t have clinical endpoints.
To validate new targets, to figure out how the product works, whether it works in certain diseases
better than others, and it’s really quite critical - in all the studies we’re doing to actually have this on
the front end to have all justified it and validated it.
This is the first thing I saw when I met colleagues from the University of Calgary – we showed this
slide for the first 3 years we were a company, where we had our friend the mouse with a tumour on
its hind flank and then our friend the mouse after treatment who didn’t have a tumour any more.
And equally this is a very early indication that you might actually have something, but it is an animal
model. Animal models aren’t humans of course, but unless you pass this threshold you really
shouldn’t be trying to move that into humans.
And there’s been a large number of publications. Again, this is a very tiny sample of the publications
that have come from either direct collaborators of ours where we sponsor their research,
collaborators where we just supply product, and from a researcher perspective you can’t imagine
the luxury of being supplied clinical grade material of a product – it’s in human clinical trials to do
animal work with, or even tissue culture work with, it’s really… They’re getting the same end product
to work with that we’re treating human beings with, it’s very important.
So this is just an example. These have all led to clinical studies. These are just samplings in each of
the areas. There are actually more things, I won’t go through them, the second one is one of those
examples where we actually treated humans as the [?] – that’s the NCI study from where they did a
preliminary report last year and they demonstrated that if you give Reolysin intravenously it
replicates in the peritoneal cavity in tumours which was a big step forward.
Lung – we’ve done quite a bit of work in different lung studies. Head and neck of course. That’s
actually a fairly early publication and it was the first time you saw the word ‘squamous’ being used
with respect to Reolysin use.
Sarcomas, [in] which we’ve had an active ongoing programme for many years. It’s had other uses of
course. Colorectal which we’re running an early stage clinical study right now. Gliomas [in] which
we’ve run 2 phase 1 studies, and I’ll talk briefly about them in a minute, talk about where that’s
going.
Pancreatic cancer, in which we’re running two clinical studies, and, as of yesterday, the NCI
committed the funding to do our first haemopoietic study, and that was again based on this
preclinical work that allowed them to justify going in and funding a clinical study.
And we continue to do this – the message for us is that it’s all an ongoing programme – expect to see
more publications; expect to see more basic research funded, supported, cajoled, however we have
to do it, from Oncolytics with Reolysin. I think it’s incredibly, critically important.
Clinical studies. We’ve run a very large number of clinical studies, and sometimes it’s a little difficult
tying together why we did some of those. Rest assured, there were reasons to do all these things
and they do tend to flow.
What I thought today I’d do is actually show the flow of clinical studies that feed into specific later
stage studies or earlier stage studies that we’re doing in specific areas so that people could actually
see the rationale going on behind this and of course … I’ll start out with our Phase 3 study in head
and neck and I’ll start from the bottom.
When we started our clinical programme it was thought that it would be safer to stick the product
directly into tumours rather than giving it intravenously and so our first two studies were, our first
study was an all-comers study in Canada, REO 1. Dr Gordon Morris was the principal investigator
followed up by a translational study in essence, sort of a phaseless study, that was constant dose, it
was really a Phase 2 looking at early stage prostate cancers, where we were treating the prostate,
injecting the virus directly into the prostate gland then excising the prostate gland and looking at it
histopathologically. And that confirmed that the virus didn’t actually kill the surrounding healthy
tissue, which is, sounds mundane, but is hugely important. People at that time were sensitive to the
fact that we were treating very ill people with virus. No matter how safe we thought it. And that
confirmed we weren’t going to get bystander effects.
From there we were allowed to then go into IV studies. We ran REO 4 and REO 5 which were
relatively parallel studies, the UK study being bigger, looking at Reo as an IV product by itself. And
then we ran a Phase 2 study in sarcomas that had metastasized to the lung, with again Reo as a
monotherapy.
That study had 2 purposes. The purpose on this flow was to confirm that Reo could be given to
patients as a monotherapy for very long durations of time. Some of the patients on this study were
treated for 32, 33 months, monthly 5 dosages in a row of Reolysin, so it was a very long exposure
and showed very nice tumour stabilisation, and that’s very, very important for the second part of our
Phase 3 study which I’ll talk about in a second.
We then said OK we’re focusing in, we’ve got the elements. We ran a head and neck study that
morphed out of a Phase 1 into a Phase 2 in the UK, which was on our now standard carbotax
platform. We had to do the Phase 1 part to see the toxicity. That, in parallel with yet unannounced
results from our REO 15 study, which is the Phase 2 head and neck study in the US, which was run
basically to confirm the data we saw in the UK, and that finally led to our Phase 3 study in Reolysin.
So what you have is, we showed we could do it intravenously, we showed it was safe, to live tissue,
we then showed it was safe and appropriate in IV. We then showed that you could treat for very
long durations with the product as a monotherapy. Then did the drug combination, showed it was
active in a Phase 2 environment, and then started this Phase 3 study.
So, the head and neck element of the attention was demonstrated in these Phase 2 studies. The
second was the often not talked about part of this Phase 3 study is that all the patients, after they’ve
finished 8 cycles of carbotax plus Reolysin are then eligible to go on long term maintenance therapy
of Reolysin by itself.
And so basically it’s a separate study within a study if you’d like to think of it that way, but you
needed to know what the effects of long term Reolysin monotherapy use IV was, which is where the
sarcoma study came in. So that’s how that meshes in with that.
And so you have this sequence - you look at the drug therapy in combination with the IV elements in
combination with the safety in combinations and this whole flow led us to our Phase 3 study.
If Reo had only been used in a sequence to get to head and neck this would have been the same
clinical path that we have taken.
And of course just for some historical context, it’s [?] and I don’t think it’s accidental – this is from
our very first clinical study, REO 1, with a head and neck patient treated at the lowest dosage which
was 1x10**8, which is a thousandth of our IV dosage on a daily basis where we have this lovely
superficial head and neck tumour on the back of the patient. This is actually a biopsy so it’s got
nothing to do with the disease that resolved very quickly and so very early on we knew we had some
sort of inclination that there might be something of interest with Reo and this was as a
monotherapy.
And of course, at the end of that it’s our survival curve from our REO 11 Phase 2 study out of the UK.
With this Kaplan-Meier curve we’re comparing ourselves to a similar patient group treated with
cis/docetaxel by Spencenier which was a publication last fall. And so you’re progressing from this,
we thought, superficial tumour, going to looking like we’re giving lifespan benefit to patients.
That’s a nice sequence, that’s where we need to be, honestly.
One of the early things that we found in these head and neck patients was we started to see our first
real indications of metastatic disease responses, and this is actually a very early patient in that study.
We have gross metastatic disease, but this is the liver – this grey zone and all these dark spots are
mets, which unfortunately is most of this person’s liver – and very rapidly you get this nice – post-
cycle 2 is only what, 4 weeks out, you’re getting this lovely response and that’s maintained. And so it
was a very early indication that we were actually getting metastatic disease response, and we saw it
in a number of other cases.
And this is a later patient, again with a large liver lesion. Heavily treated patients, we were getting
these wonderfully long, quite durable metastatic lesion responses.
Just to show that it does work on primaries. This is the case of a patient who wasn’t a surgical
candidate – he had a large primary tumour on his neck – and again a very rapid response, which is
becoming characteristic of when you do get a response with Reolysin, getting these long very, very
aggressive responses.
Now you can view the same kind of flow with all our other studies, and I think it’s important to do
that. Pancreatic cancer – we’re running two studies right now: we’re doing a single arm study in
combination with gemcitabine, and our colleagues at the NCI, our sponsor, are running a
combination study in first line patients with a carboplatin paclitaxel combination. That one is unique
in the fact that they’re not using the standard of care in the first line. So they’re not using Gemzar.
I’d just like to point that out – the control arm here is not … there’s no Gemzar involved, it’s carbotax
alone.
But how did we get there? Same sort of thing. We had – if you were just looking at pancreatic cancer
in isolation, you have the same, much the same sequence but with slightly different purposes. You
went through the same intra-tumoural studies –you had to show that you didn’t have bystander
effects. Well, we did that in those first two studies, primarily the second one. Then you looked at the
IV studies – the same critical path – to go IV you had to show IV monotherapy.
Then you go into the sarcoma study. Again the same sorts of things, where you’re looking at the long
duration monotherapy exposure in a Phase 2.
Then you switch. Then you’re looking at, well, before it was carbotax toxicity, now we did a Gemzar
study. And we did a Gemzar toxicity study in the UK which has higher dosages than we use in North
America – they’re about 25% higher dosages – so it’s a pretty extreme case of Gemzar combination.
And that fed into our single arm Gemzar pancreatic study that’s now ongoing REO 17. The other
study requires the same toxicology data, so basically you’re double-using the same study where you
did a Phase 1 study that’s morphed into a Phase 2 study with carboplatin paclitaxel focusing on head
and neck, but in this case the toxicity data is what allows you to do the randomised study with
carbotax.
So again, if all we were doing was pancreatic cancer, you’d have basically the same flow. Minor
tweakings with it but it’d be pretty much the same clinical flow. So it’s really important I think to
know how that feeds in and gets to those places.
Now, a little specifics why we’re interested in pancreatic cancer. It’s the one cancer where the
primary solid tumour has such a high RAS activation, which is the basis on which Reolysin works.
Over 90% of pancreatic cancers specifically have mutations at KRAS, and there are some smaller
percentages obviously of other activating mutations. And so it’s one of those cases where you don’t
even have to think about pre-screening – if you have pancreatic cancer, it’s likely it’s going to have a
RAS involvement, which means it’s likely Reo should work in it.
The single arm study is in patients who have advanced disease or metastatic disease and who are
treatment-naïve at… It’s sort of a dark joke in pancreatic cancer that there are no second line
patients because they don’t live that long unfortunately, and so most of the studies you see are first
line.
The primary endpoint was to see 3 or more patients with stable disease in the first 17, and we were
extremely pleased to see that we met, actually exceeded, this endpoint in the first 6 patients we
had. 3 stable diseases in 3 patients, and a PR in 1 patient, and that’s pretty remarkable given that we
were expecting to see that with 3 times as many patients. And we’re finishing off that study right
now. So that’s our pancreatic programme.
Laid on top of that is a very exciting programme where we’re looking at a randomised study paid for
and sponsored by the NCI where we’re looking at carbotax vs. carbotax/Reolysin in basically the
same patient population. It says recurrent, but again, as I just said, we don’t get a lot of recurrent
disease in pancreatic cancer. That study is enrolling quite nicely now so we’re anxiously awaiting the
results of that second study. And certainly we can track that first study quite closely given it’s ours
and it’s a single arm study.
Just because they’re so rare, this is the partial response we saw on the Gemzar study, and it also
illustrates how difficult it is to grade pancreatic cancer by response. Honestly I had to have
somebody tell me where the responses are, and so there’s a lymph node response and a pancreatic
head concurrent response, but again, very quick – it was after 1 cycle.
If we go on to our brain candidates, brain cancer - in this case specifically GBM – was actually our
first real targeted indication. And what we were doing initially was to inject the virus directly into the
tumour bed, which is a surgical procedure – you drill a hole with a dermal drill in the head, or if the
patient’s already open – and inject with very fine-tuned injection methodology, virus directly into
the tumour, a bolus, just squirting it in.
That was actually our first study. We, I think naively, thought that that would work quite nicely
because it worked wonderfully in animals. What we didn’t really realise at that time is that delivery
of the virus would become so critical: the virus works quite nicely when it’s near cells that are of the
right nature, but it has to get there, and in this particular study which was our first under REO 3, we
saw indications of activity, which was nice, but didn’t get the best response rates on the planet.
We then said, OK, we have to improve delivery and we went on to our REO 7 study in the United
States. This study had a higher top dose, which is important, but it also used an alternate delivery
method, which I was going to show, but after polling everybody who looked at this talk, 50% of them
said ‘Do not show that picture in public, Brad!’ It’s quite off-putting actually, it’s enough to make me
not want to ever have that surgery.
In this case you’re infusing the product through a number of different ports that have been surgically
implanted in your head. They’re writing up the publication now on this study, but it did improve it,
that’s the conclusion, but not to the point where we thought it would.
So what you’ve got is your sequence – we had to show it was safe in intra-tumoural because… and
then we went directly to intra-tumoural specifically which was REO 3 in Canada said delivery wasn’t
what we thought, so let’s infuse it and see if that improved, and it did, and then say well, gee, and
we knew this fairly early on in this study, that we were seeing this. It’s still not good enough. The
delivery still isn’t adequate to demonstrate it. So then you have to think about doing it in a more
convenient and better way which is probably IV so then you go back and say that you can reuse the
IV data that you generated for other studies, the IV monotherapy studies in the US and the UK and
then you say how do you get the virus across the blood-brain barrier?
Well, guess what? You can actually use some of the things we’ve also used before, like radiation –
actually it’s pretty good at altering the permeability of the blood-brain barrier, so we had our 2
radiation studies in the UK and coincidentally a lot of the chemotherapies that we use do also the
same thing. And so you take a look at again you know our chemotherapy studies.
And so what doing right now is planning at looking at, in a very cost-effective manner, ie somebody
else will be paying for it. Looking at… I don’t know if anybody else has noticed it but we’re getting
pretty good at getting other people to do clinical studies.
Looking at delivering reovirus which looks like it works pretty well in brain cancers and probably
brain mets in an IV fashion, and finding a way to get it across the blood-brain barrier in an effective
manner, which is a very large market. I don’t know if anybody’s noticed but the increase of cause of
death by brain mets in cancer is increasing. It’s not that brain mets are getting more common, it’s
that we’re selecting for brain metastasis because many of the drugs that we use don’t cross the
blood-brain barrier and so we’re treating systemic disease quite nicely and what we’re leaving
behind is brain mets and that’s what kills the patients. We’re enriching our patient population for a
different cause of death.
This is quite exciting, but it’s long term obviously – we’ve been doing this since 2000 and we’re
finding that delivery does count pretty much everywhere that we look. It’s longer term and it kind of
moves along in the background, but I just thought I’d draw attention to it because we don’t talk
about this particular ailment very often.
And this is out of the US study. This will be in the publication and again we have a genuine – and it’s
really hard to see here so I should have circled it – 2 different cuts of the before and after – quite
long duration and partial response in glioblastoma multiforme in a patient treated with
monotherapy Reolysin infused into the head. You can induce partial responses in gbms that are long
duration with reovirus. That’s a pretty important conclusion, and our investigators are all pretty
excited about moving on, about trying to turn this into a real therapy.
Ovarian cancer. Again we can do the same cycle and hopefully me talking about these will shorten
down quite a bit. You run through the same sort of things – you had to show tumour bystander
effects, you had to show you could do it with IV, you had to show you could do long term therapy.
And then you switch over and say specific and that’s where the NCI monotherapy study which they
presented last year at the AACR or ASCO it was earlier in one of the publications. They showed if you
give Reolysin as a monotherapy it gets into the peritoneal cavity and infects and kills ovarian
tumours. That’s a pretty remarkable conclusion.
Then you look at the drug combination and we did a Phase 1 study with not paclitaxel by itself, but
docetaxel and, for those of you who are involved in manufacturing and sale of taxanes, I apologise
for saying they’re pretty much equivalent. You may disagree with me but, they’re taxanes. And so
we’re now doing this randomised Phase 2 study. It was based on all of this, going forward, with the
NCI again paying and sponsoring for a randomised study in paclitaxel vs. paclitaxel-Reolysin in
ovarian cancers. Again based on this sequence of flow.
And finally (I’ve only 2 more of these) you can do the same flow with colorectal cancers. Again the
same starting point – intra-tumoural. 2 intra-tumoural studies, the IV studies as monotherapy, long
duration as monotherapy, and then our translational study which we just announced recently, the
results, they were looking at Reolysin monotherapy to patients who are surgical candidates for new
adjuvant use of Reolysin. The patients got treated with Reolysin as a monotherapy and then they
excised the metastatic lesions in their liver and looked at whether the virus infected and/or killed the
tumour.
And out of the 10 patients they treated, it was like 8 or 9 out of 10 (the final number they’re arguing
about) actually showed evidence of that – either total tumour death or partial tumour death with
lots of virus replication. Pretty remarkable for a monotherapy in a metastatic disease, but what that
does, that leads in to doing the first combination therapy and we had to go back to Phase 1 which
we’re in the middle of right now in combination with the second line standard of care in the States
which is folfuri, which is also used in the first line in Europe quite comfortably.
So again it’s that flow to get you to a major indication, and this, if successful, is one of our candidates
for us to do our own randomised study as a follow-up.
Just to show you one of our earliest patients in the UK IV study, so that would be REO 5, there’s an
antigen that you can follow, CEA, that’s indicative of a couple of cancers, but colorectal cancer,
metastatic colorectal cancers, is one. And the treatment cycles with reo as a monotherapy, you can
track between a 75% and 80% regression or diminution of that antigen, which of course started
coming back because we weren’t treating all the tumour because we weren’t getting all to it. But it
demonstrated early on that Reo again could be used IV to treat colorectal cancer and this is more
directed towards the primary.
Colorectal cancer is very interesting for everybody – it’s one of the major indications. Second line
therapy in the UK or in the US is typically folfuri plus one of the EGFR inhibitors but if they have a
mutation at the KRAS gene itself, which is almost half of them, then the EGFR drugs are thought not
to work, or work poorly, and so that’s our patient population because then they don’t have a
standard of care.
And so that’s what we’re directed or looking primarily at in our US patient population. In the UK if
we ran a study there we can actually move up to first line if we choose because they do not use
Avastin in the UK. And so we’re doing this Phase 1 study looking at Reolysin in combination with
folfuri – it’s 2 different Reo dosages and 2 different folfuri dosages.
And this slide I talked about earlier. The, I guess it’s 9 out of 10: 7 out of the 10 had viral replication
and another 2 had complete tumour necrosis which you would infer was due to something – that
doesn’t happen by itself. And what’s important, if you’re connecting this with our metastatic
thoughts, over half the patients, about 60% of colorectal patients actually metastasize to the liver, so
it’s an interesting conjunction.
If you look at metastatic disease, and I’ll briefly talk about that, because we’ll be hearing more about
that later this year, if you grade our Reo Phase 2 study in the UK just for metastatic disease, so
you’re looking at metastatic disease not in the brain but in the liver, the lymph nodes and the lung,
you get about a 40% response rate, and an 80% stable disease or better rate.
Generally for metastatic disease it’s thought that single digit response rates and stable disease
around 15-20% is far more the norm using conventional therapies. So this is markedly different than
what you would expect to see, and so we’re increasingly focusing on at least measuring this
independently from the overall response rate to see if that matches up going forward and if it does I
think you can expect to see us focus even more of our time and attention on metastatic disease.
Metastatic disease is what kills people primarily in cancer patients – probably 90% of cancer deaths
can be traced to metastatic disease, so this is an important element.
Finally, lung cancer, for which we have 2 studies going on right now. We have a single arm study
looking at squamous cell lung cancers, which wasn’t a market several years ago – they were lumped
in with all non small cell lung cancers until Avastin and Alimta didn’t do so well. And so it fractured
the non small cell lung market into a new category and this is about 30% of all non small cell lung
cancers. We have a single arm study looking at squamous cell in combination with carbotax again
with Reo, and our non small cell lung excluding squamous cell study that we’re prescreening for
EGFR and KRAS and the preliminary data on this will be presented in July in Amsterdam at the Lung
Congress.
These 2 studies use the same drug combination and are both ongoing at this time. Again you can
make the same story for the sequence. Many of these studies get reused over and over again to lead
to different indications. Local tumour therapy, the IV studies, as a monotherapy, long duration
exposure in a Phase 2 environment, toxicology and early efficacy data in squamous cell head and
neck (which as you can imply is related histopathologically – they’re the same disease, just in
different areas). For head and neck, looking at carbotax, and that leads you to pure Phase 2 studies
where you’ve got toxicology, you’ve got indication of activity and in broader cases of activity than
you might expect.
This is from our head and neck study but is lung metastatic lesions, so that the primary regresses
quite nicely and you’re getting all these lovely little metastatic lesions completely responding in the
lung, so from a different study you’re getting indication of lung cancer ‘activity’ even though they’re
metastatic lesions. So quite encouraging early on and that transposes you into lung studies from a
different study, being head and neck.
And then I’ve done the pure head and neck study. This is actually our very first squamous cell patient
which we were all a little surprised to see on Fox News for the first time to find out we had a
response. A little awkward when you’re doing freeze frame on television news segment trying to get
the screen showing a scan so you can see what’s happening with your patient. And while this is nice
we did inform the investigator he really shouldn’t be doing that. His motives were pure, however –
he was just trying to get the word out that this might be interesting to help his enrolment. But again
you’re getting this very bulky disease. This is the tumour here that resolves quite quickly – this is
only again 5 or 6 weeks for the scan and then it’s gone and metastatic lesions as well.
Our initial inclination from the head and neck responses in the lung then transposed into squamous
cell of the lung responses as well.
Always talk about safety. Oncolytics is, I think because it’s a live agent, focused on safety rather
markedly. We’ve treated just over 380 patients of our own now; the NCI has added probably about
60-70 patients – in that range – it keeps going up daily at the moment, so it’s hard to keep track.
Most of these now, about three quarters, have been treated intravenously, the rest, who were the
early patients done intra-tumourally. We still don’t have an MTD, and the [side effects of the] virus
by itself, you know it’s tough to separate them out when you have drug combinations, are pretty
mild generally. The most common side-effects are what we’ve named pre-flu syndrome, which has
actually caught on as a term that people use. It’s basically what you feel like the day before you get
the flu – you get a mild arthralgia, mild fever – a degree or two degrees, grade 1 or grade 2 fatigue,
and the major blood chemistry changes typically are lymphopenia, neutropenia, low grade and they
typically resolve quite quickly.
It’s a pretty standard reovirus monotherapy side-effect profile and if you look at pretty much every
other agent that’s out in the market or in development it’s a far superior safety profile and I think
it’ll be a major asset again going forward. To have gone from intra-tumoural, to our first IV patients
which were treated in the UK in a negative pressure suite with people with space suits on, to
patients being treated in open wards as outpatients being sent home. So they’ll have their colleague
patients sitting there watching them get reovirus then go home in a cab or whatever and come back
the next day and get treated, it’s really… And that’s a result I think of this focus on safety, and
certainly Dr Gill has been involved with this from the very start and I think I would attribute a large
amount of this particular profile focus onto George. Thank you. It’s critical. You have to be obsessed
with this.
With respect to future directions for the company, just very briefly, and this may sound a little
‘motherhoody’ (but that’s because they are) – biotech companies spend money, to be candid, that’s
what we do and at the end of the day when we quit being innovative quit doing product
development, it means we’ve been successful and that point is when you quit spending money but
for now we’re a development stage company and we need to support our operations which means
we have to finance ourselves, so it’s important that we maintain a strong balance sheet.
However we do that, whether independently or through a variety of other means – partnering
programmes, or getting other people to pay for clinical studies, or whatever – to support our
programme. Critical. As I implied at the start of this talk it’s absolutely essential we continue to add
and build upon our IP portfolio – we are not in the ‘wind down’ part, we are in the ‘wind up’ part on
this particular programme.
Manufacturing is the core underpinning of whether in the end we’re going to be successful with our
product filings. Absolutely essential that we continue to finish process validation this year, begin our
conformity runs, and then begin to stockpile product for potential eventual sale. The worst thing I
can imagine is that assuming Reolysin gets approved, on the day of approval Matt walks into my
office and goes ‘Oh we don’t have any product to sell to anybody, so we’re going to have to do a
lottery or some equivalent programme’ and we do not want that to happen, we do not want to be
product restricted on the assumption that we’re actually going to be successful.
We will continue, we continue to do so, to sponsor research which allows us to get into new areas,
as evidenced as recently as yesterday with the multiple myeloma study which would not have been
funded by the NCI unless we did this.
And finally, very specifically, we will focus obsessively on the execution of our head and neck study
this year, our Phase 3 study. That’s the front end of our programme, it’s absolutely critical and right
in behind that to decide on, to begin 2 randomised studies of our own in new indications, in behind
that, with the intention of having those up and running prior to us getting our first data out of our
Phase 3 study. Absolutely essential.
For this conclusion, over the last ten years I think we’ve been relatively successful in a number of
things. We’ve raised the resources to keep Oncolytics focused on its programmes, and I think it’s
critical – obviously we wouldn’t be in business if we couldn’t have done that. And we’ve built an
impressive intellectual property portfolio. We’re at, and really can’t emphasise this [enough], we’re
at the low end of commercial scale manufacturing already in place and we’re not going to have to
play catch-up on this, which is impossible to do, honestly, when you’re in a Phase 3 study.
We continue to support our basic research and there’s literally dozens and dozens of research
publications out there as a basis of that, which serve 2 purposes – one to support new clinical
studies, but also helps recruit and educate the medical community to this interesting new concept.
And finally, we have currently 3 randomised studies. Our Phase 3 and 2 NCI studies and about to
have that balloon to 5, which is… To have 5 randomised studies in 5 different indications at the same
time is I think an impressive achievement from a biotech company.
So that is all I had to say today. Hopefully you found that historical perspective somewhat of interest
and certainly it’s been an interesting 10 years, I have to say, of active operation over 10, 11 solid,
active years. And when I think back to when we started up in the summer of 1999 with Matt and I,
and we went public with Matt and I as being the only 2 employees, which was interesting, to where
we are today, where we’re running, by this summer we’ll have a Phase 3 study running in 11
countries with collaborators around the world and having run literally hundreds and hundreds of
patients is quite a transformation. We’re very excited, we can see the finish line, we can see the end
and I think our job for us now, going forward, is to execute our plan and so that’s what we’re
planning on doing.
So again, thank you for your time and attention, and I’d be happy to entertain any comments or
questions that you may have.
QUESTIONS AND ANSWERS
48:15
Q: Zero long term debt, is that correct?
A: Yes. Our very first heritage grant, which was a couple of hundred thousand dollars has a repayable
feature if we start selling product, so that’s not classified as debt, so that’s it. We try to keep things
simple – we have 1 class of shares, we have common shares, nobody has preferred rights, nobody
has better rights than somebody else, no weird convertible debt or any of those other kinds of
things. We’ve been fortunate.
Now let’s just be honest – if those were the only financing tools available, we’d do it, but we’ve been
fortunate I think not to have to resort to those tools.
49:05
Q: Would you hazard a guess about what the survival curve for the UK Phase 2 head and neck study
would have looked like if you had had a maintenance arm.
A: A guess, and an optimistic guess, and honestly Matt and I joke about this fairly often my belief in
Reolysin isn’t any greater than the day I first saw Matt’s mouse model, which means [incoherent]
but I would expect that that would have shifted the curve over. I mean that study was unfortunate in
that we only planned to treat the patients for 8 cycles, which is about 6.2 months, and there were
two reasons for that.
There were some product limitations, availability, and there was an acknowledgement that these
patients were unlikely to even live that long, much less be responding that long and we needed to
cut off the study, you know, so we could actually say ‘We’re done’.
You might imagine our surprise when most of the patients at 6.2 months were not only alive, but still
responding and had to be told they weren’t getting more Reolysin therapy.
If you translate the sarcoma Phase 2 data to that and say that’s your starting point, our anticipation
is that for the responding patients you’ll probably get some maintenance of response from the
maintenance therapy and that’s why we introduced it in here. So I would expect it would push that
survival curve more off to the right, which is the right direction for a survival curve. But we’ll see.
We’re trying to ensure that study has the best possible survival in the test arm.
50:48
Q: Could you give us some more colour commentary on what the discussion was like with your
warrant holders? Did they call you first and say, you know, we’d like to give you a gift?
A: They weren’t really giving us a gift. For those who don’t know, we did a financing in November for
$4.70 a unit that had a share at that price and a half-warrant exercisable at $6.15. And our now-
largest shareholder was part of that financing.
And I honestly can’t remember if they brought up the subject or I brought up the subject during one
of my regular updates with them about the possibility of exercising those warrants very early. I
mean, I think they exercised them when we were trading at $6.20 or something, so very uncommon
– much before they expired – to give us the wherewithal to do potentially one extra small
randomised study. A hugely supportive move on their behalf I have to say, and for somebody to do
that is I think a real measure of the support of that particular shareholding group.
And so we’re quite pleased with that – it doesn’t happen very often – usually the pattern is that
warrants are 3 hours away from expiring and you’re getting enquiries about ‘Do you have the
warrant certificate?’ ‘Do I have warrants in your company?’ You know, those kind of things. We
laugh – Doug has had those phone calls – literally – sometimes after they expired. ‘Did they expire
yesterday?’
That’s far more the norm, so to have a shareholder put their stake in the sand and give you $8.1M or
$8.2M when they didn’t really have to is really beneficial, and being very helpful.
52:45
Q: Do you mind commenting on analyst coverage please?
A: In Canada we have analyst coverage from most of the analysts who cover biotech, so I won’t go
through the whole list. And in the United States we now have Rodman and Renshaw who’s covered
us for quite some time, and just recently Wedbush initiated coverage on us as well.
Historically we’ve only done 1 financing that had a small US component and so our financings have
been done, with the exclusion of that 1 small component, all in Canada or in Europe and so I think
the analyst coverage is reflective of that financing shareholder base. I expect that to change over
time – there’s more and more interest over on the US side.
Often the majority of our shares on any day trade on the Nasdaq not on Toronto these days and last
year was I think the first year we traded over the year more shares on Nasdaq than we did on
Toronto so we’re starting to see a shift of our shareholder base, at least through trading into US
hands. So expect to see more US coverage is the short answer.
54:00
Q: Why is the multiple myeloma trial Phase 1?
A: It’s a very good question. It’s a dose escalation Phase 1, I think they’re starting at 3x10**9,
1x10**10, and 3x10**10 I think is the sequence. Those patients are a very unique sub-patient
profile. Multiple myeloma, and excuse me for sounding a little professorial here, for those of you
don’t know, is a cancer of antibody-producing white blood cells, B cells, and so the patients tend to
be somewhat immuno-compromised just by the nature of the disease.
The therapies to treat it aggravate that, because they’re killing off your B cell populations so you’re
antibody deficient. They treat it with things like prednisone, which is immuno-suppressive, and
specific agents that knock out those things. So this patient profile – they’re different from what
we’ve treated before. They tend to be immune deficient in a way that you really have to examine
what’s the case there.
The NCI study has 2 components that are important. One is to demonstrate safety, which is always
important, but the second one is to show (on the positive side this is a non-solid tumour so you
would assume you’d have less delivery issues than you would for Reo trying to get through a solid
tumour) evidence of the virus replicating in a human setting, in a clinical setting in tumour cells.
Multiple myeloma certainly and lymphomas in general in animal models have shown to be
reasonably amenable to reovirus treatment, so it’s an area we’d like to have gone and done
ourselves, but limitation of resources and so on…
I have to say, we’re terribly pleased with the attention the NCI is paying to this particular agent. We
have, what, 6 studies now, including 2 randomised studies, and probably more to come, that the NCI
has paid for through CTEP [Cancer Therapy Evaluation Program], the office that manages this.
That’s a very large commitment for a single agent in mid-stage development from their perspective,
so I think it’s a pretty big statement of support. But that’s why we’re doing the Phase 1. They’ll get
through that pretty quickly – there’s not a shortage of patients unfortunately in that particular
group. Then I think the anticipation is that they’ll move, as is their wont, once they’ve assured those
things, to move into drug combinations, which is where we want to be as well.
56:34
Q: Do you have any updates on the enrolment for the Phase 3 trial? I think last year you mentioned
you were going to be providing updates.
A: Which I honestly shouldn’t have. What we’re doing is providing updates, if you want to look at
clinical trials like gov [http://www.cancer.gov/clinicaltrials] on sites that are open. Our job in that
Phase 3 study is to get the number of sites required to get the enrolment done expeditiously up and
running, and that’s what we’re focusing on and reporting. We just don’t think it’s appropriate to be
giving blow-by-blow updates on enrolment.
Enrolment is not linear in clinical studies, you don’t enrol the same number of patients every month,
it tends to be more of an exponential curve, which is very typical, and that’s how this study is
working out. So I think I probably shouldn’t have said that last year, so I’ll withdraw that and admit
that I shouldn’t have said it and focus on the thing which counts, which is us getting into more
countries: we’re approved in 6 countries now, including France last week and that’ll be 11 probably
by the end of the summer. In each country post-approval you start opening up centres, which we’ll
continue to do in Canada and the United States and the UK and other jurisdictions we’re already in.
That’s our task this year. Get that site number up. Get the enrolment on the first stage done and
then move into the second stage of the study.
58:06
Q: Can you give a brief update on the US head and neck trial and where it’s at, and what’s going on
with that?
A: We announced we finished enrolment. Still tracking patients, or patient I guess – this is the last
patient – and once we’re done that we’ll report on it. That’s the nature of our area – until the
patients are done, the patients aren’t done yet. I would expect some time this year we’ll be hearing
about the data on that study.
The key part of that study is to try to confirm what we saw in the UK Phase 2. It’s been a little
overrun by the Phase 3 study, candidly, but it’s still an important study, to have a different
jurisdiction pretty much confirm what we saw over in the UK and that was its purpose.
58:52
Q: A follow-on question. I thought the protocol was a little bit different for those two – one was
taxane naïve and one wasn’t. Is there…?
A: The protocols weren’t specifically that way. Most of the patients in the UK turned out to be
taxane naïve, not all of them, some, as you see in a couple of slides, had seen taxanes a number of
times – it didn’t really seem to change things.
In the States more of the patients have seen taxanes usually, so more of the patients on that study –
we started actively seeking them – have seen taxane prior exposure. Everybody assumes the
response rate will be different because they’ve seen taxanes, or not, and there’s a lot of argument
about it in the area, but none of it based on data. So having a study [in which] at least in some ways
you can compare previous taxane exposure in patients versus non- will be very helpful.
Our Phase 3 study is platinum refractory, taxane naïve patients and we’ve been obsessive about
resisting attempts to expand the enrolment criteria, because it’s our belief that many of the earlier
head and neck studies that have been run have not shown what they might have shown simply
because of the patient profile – they mixed second and sixth line patients; they mixed patients that
are platinum refractory with platinum resistant; and taxane naïve to taxane induced patients and
taxane refractory patients, and and and and and…
You can’t do that. Well you can, and then you don’t get anything. So our obsession, focus, insistence
is that patients have that very tight enrolment profile because we think it gives us our best shot at
demonstrating activity [?] in our Phase 3 study.
60:33
Q: One more question. The randomised pancreatic study. A couple of times you’ve hinted that it’s
different or special in a way to have Gemzar not being used as the standard of care. Can you expand
on that?
A: With apologies to my colleagues who developed Gemzar and Eli Lilly who sells Gemzar, many
people in our field believe that Gemzar was approved for use with pancreatic cancer on a statistical
anomaly not on real signal. It provides a few short weeks of benefit.
Now, if you’re dying of pancreatic cancer, a few short weeks of benefit is the most amazing gift there
is, so I would take Gemzar too, honestly, just to be up-front, but it’s not a huge amount of benefit
whether it’s real or not. And so I think the feeling is that alternatives should be explored that may
not include Gemzar, and that’s the rationale for this particular study.
We were delighted the NCI wanted to do that, but you’ll notice in the background we’re still running
a Gemzar-Reo study, so we’re going down two paths at one time, the assumption being that we’re
hoping we see superior responses in the Gem-Reo study and we’re hoping to see carbotax-Reo beat
carbotax. But there’s some expectation because taxanes seem to have some activity in pancreatic
cancer that… A carbotax arm by itself will probably beat Gemzar by itself, but we’ll see. I think
everybody’s watching that study for that reason.
That study is also interesting because it’s not blinded, it’s randomised but not blinded because all
the patients in the control arm when they progress they then cross over and get carbotax-Reo
instead of just carbotax. We have already had patients in that study do that, which is interesting. You
get first line and this new category called second line, data in drug-failed patients. It’s quite unique.
Those studies are getting more and more common in oncology to derive information earlier than
you might have in a blinded registration study mode. We’re very excited about that and any
information we can glean out of that study, we try to, because we can. It’s very exciting.
63:03
Q: Today’s announcement about Sigma-Aldrich and the manufacturing – does that telegraph that
you’re betting or speculating that the FDA will approve before Europe, or should we make any read
about the probability or the timing of the two venues in terms of registration approval?
A: It has no impact on the bet whatsoever. This Sigma-Aldrich facility, the Sigma-Aldrich capabilities
are equally applicable to a European filing as to our US filing.
SAFC is a very good organisation. It’s invested a lot in a facility that they purchased and retrofitted
primarily for our first tenant use. It was a fairly big commitment on their behalf on an agent that was
fairly early when they did that, and with no other clients to fill it at that point in time – we were it at
that point in time. So I think it’s a pretty big commitment on an experimental agent at that point in
time.
But they certainly have the capability of taking that through into other jurisdictions and Matt’s team
is focusing very strongly on making sure that the validation and conformity runs are pan-
jurisdictional. So if one jurisdiction has a higher standard than another, then you go to that
automatically.
Europe is different from the United States on the things that concern them, and different countries
in Europe are different – it’s not a monolith – you wish it was a monolith but it is not – so there’s
different concerns and you just pay attention to them all. Things like water for injection – if you do it
by distillation in one jurisdiction that’s great and if you do it in Europe (or maybe it’s the other way
round – I always get them mixed up) you have to do it by reverse osmosis. Just two different
techniques to get to the same place so you use WFI that’s made by both and that solves that
problem.
Little tweaks like that you just pay attention to, and SAFC is very good at paying attention to those
since they make product for multi-jurisdictional use for a very large number of companies. They’re a
good firm. I hope that’s a good enough advertisement for SAFC. I would encourage every company in
the world except for our other viral company colleagues to use them for what they’re doing…
65:41
Q: The Amgen purchase of OncoVex. Could you do a little compare and contrasting, I mean the
manufacturing differences, their agent is…?
A: Completely different agent. It’s a genetically engineered herpes virus that’s had the 34.5 site
chopped out of it because all herpes has to have the neurotoxicity region chopped out of it before
you can stick it into human beings, which seems commonsense to us in the field.
So it’s comparing apples and oranges – the only thing in common is it’s a virus but everything is
different about it – it’s a different virus, it’s got a different mode of action, it’s got a completely
different manufacturing process when you get down to the fine detail points.
Amgen is very good at manufacturing – I know Amgen quite well and if there are any manufacturing
issues I would expect they’ll fix them. I don’t know if there are or there aren’t but certainly if
anyone’s going to take care of it, Amgen will.
We were all very pleased to see that development and while Reo works quite differently than their
product and has different target indications and, and, and… it is a virus used to treat cancers and it
provided for, I think, a, validation is the wrong word, but a relative validation of the area. That big
pharma, because Amgen isn’t a biotech company any more, was willing to commit those kind of
resources to a colleague company was quite helpful I have to say for us all in the area.
67:20
Q: Does the mechanism that their virus uses to avoid being shuttled out of the cell – is it a totally
different mechanism of action, or…?
A: Literally every virus is different. Its recognition by the immune system is different, the means by
which it’s cleared by the body, immune or not, is different.
I mean, Reo’s early clearance has got nothing to do with the immune system – it’s basically just
mechanical filtration and is mostly the lung and the liver. If I gave it to you it would be gone in half
an hour – that’s not your immune system, I’m sorry, it’s different.
And then again Reo, in normal healthy cells there’s a specific double stranded RNA defence
mechanism that’s also not immune, so the immune system’s just part of the equation. But herpes is
very different than Reo in its presentation to the immune system, how it’s cleared, what it binds to
to get into the cell, where it replicates in the cell, everything is unique. I think you have to think of all
viruses that way – adenovirus is different, herpes is different from pox; vaccinia is different from Reo
in all those elements.
We all get together every couple of years in the virus area, have a conference and it’s very inhouse
and it’s not usually competitive because everybody knows everybody is quite different from each
other and we share a lot of things which help each other out, which is going to end some day, but
right now it’s quite collegial. It is different.
68:49
Q: One of the things that’s so stunning to those of us who are watching what you’re doing is how
broadly applicable Reo seems to be, and so… Is it just coincidental that the upfront payment was real
close to the market cap of Oncolytics? With a success payment that would double that?
A: What I find interesting, because obviously I didn’t invent this – Matt and his colleagues did – the
very first time I sat down and listened to Matt present Reo to me, what struck me was the potential
breadth of activity and that really was exceptional.
Looking at normal solid tumours, two thirds-ish have RAS activation or RAS pathway involvement.
Some outliers like panc which is over 90%, metastatic disease arguably 90% or greater, has a RAS
pathway activation, so coming in you have the scientific basis for say ‘Whoo – this should work on
pretty much everything’, and then you start digging into where it works, how it works and all those
other issues, and we’ve found out that delivery into tumours is a critical issue, just as an example.
And of course we found out in humans. Animal models are really poor substitutes for human data.
Animal models are very much more like metastatic disease in that the tumours aren’t very well
differentiated. The piece of tissue you implant in an animal, it’s not the same as a native tumour. So
we found out in humans that we had permeability/delivery issues. That sort of detail and nuance.
Very important nuance, but that was what struck me at the start – it was broadly active and if we
just learned how to use it right we should make it broadly active in people. I still believe that. I think
we’re starting to see that. We’re starting to see this pattern of 40%-ish response rates and 75%-80%
stable disease or better in patients that typically have single digit response rates, all over the place.
That’s a pretty big change.
So I think that’s what really struck me, what caught my attention, and the fact that the science has
remained consistent over all these years and has been broadened and has been tested and has come
up with the same conclusions, I think is quite remarkable and is a testament to the very high quality
early research that was done before I got involved.
71:26
Q: The NCI is not monolithic – they’re obviously seeing some of the same things that you’re seeing
and buying into it, literally. Is there some sub-group within the NCI that has really got the story?
A: I think you’ll always see a pattern with the NCI. They did all the co-therapy work to start so Matt
and I were both expecting to see the first studies being co-therapy studies. You might imagine we
were a little surprised to see a monotherapy melanoma study, a monotherapy ovarian study, a
monotherapy multiple myeloma study etc, and their point to us was that they’d like to see proof,
evidence not of clinical responses necessarily but proof that the virus can actually replicate and be
demonstrated to get tumours of different types as a monotherapy.
Once they’d established that, and that’s the pattern they did with the ovarian thing, then they move
on to drug combinations and start looking for efficacy in the traditional sense. They did that with the
ovarian, they’ll be announcing the same thing with the melanoma I would expect some time this
year, they’re looking for the same thing in their multiple myeloma studies – that’s just their pattern.
They don’t break from their pattern, they’re the NCI, they do what they do and so we follow along.
I think the level of support we’ve got from the NCI is evidence of their interest because it all comes
out of the same office, and this is in a budget-constrained environment because they’re getting cut
back rather markedly in the States right now. They’re valued collaborators of ours and we’ve learned
a lot from them and they’ve learned a lot from us. It’s a good relationship.
[Closing remarks]
TD Waterhouse Note Oncolytics in Partnership Talks
INTERVIEW-Oncolytics says in talks on partnership deals
5:09PM ET on Friday May 13, 2011 by Thomson Reuters
* Companies across the globe show partnering interest
* Could launch reolysin in late 2013 if regulators approve
By S. John Tilak
TORONTO, May 13 (Reuters) - Oncolytics Biotech Inc <ONC.TO> <ONCY.O> says it has received interest from potential marketing partners across the world for its cancer-combating therapy, reolysin, and is in discussions with several of them as it looks to launch the much-heralded treatment as early as 2013.
"We're looking to cover all regions with partnerships," Chief Executive Brad Thompson told Reuters in an interview this week.
Oncolytics, a Calgary-based biotechnology company, develops specialized viruses to treat cancer. Reolysin is its lead product and is a formulation of a human reovirus that is associated with respiratory and gastrointestinal diseases.
The company says reolysin -- a short form of the term respiratory enteric orphan virus -- is designed to destroy cancer cells alone or in combination with chemotherapy treatments. It is currently being tested on humans.
Partnerships are key for smaller biotech companies, which need the scale of global or regional pharmaceutical companies to distribute and market their products.
"Basically you engage in (partnering) activities and you run like you don't have a partner. You do those two things in parallel," Thompson said.
Thompson declined to comment on when a deal could be signed other than to say it is likely to be before the product is launched. Analysts expect an agreement much earlier, possibly this year.
"We'll do a partnership when it gives us a better financial outcome than not having a partner does," Thompson said.
The timing of regulatory approval depends on factors such as how quickly people are enrolled for studies that are underway in several countries.
Late-stage clinical studies for head and neck cancer have been approved in six countries and that should expand to 10 or 11 countries by the end of the summer, Thompson said.
"It's possible that if everything goes correctly to have product approval in late 2013," he said.
Earlier this week, Oncolytics signed a commercial supply agreement with SAFC, a unit of Sigma-Aldrich Corp <SIAL.O>, for the commercial manufacture of reolysin.
"The deal is absolutely critical for us to be ready to file for product approval," Thompson said.
The company owns a patent until 2028 that covers methods for making and using modified reoviruses and also covers pharmaceutical compositions that include them. (Reporting by S. John Tilak; editing by Peter Galloway)
SAFC Sigma-Aldridge contracted as Reolysin manufacturer
SAFC completed their construction of this Viral manufacturing suite capable of 1000 liter batches using disposable Bioreacter technology. IMO this is a very strong statement of confidence that ONCY management feels Reolysin will be approved and is preparing for commercial manufacturing.
From the SAFC news release in Oct 2009
http://www.manufacturingchemist.com/news/article_page/SAFC_Pharma_completes_12m_expansion_in_Carlsbad/43107
SAFC Pharma completes $12m expansion in Carlsbad
SAFC Pharma has expanded its contract manufacturing services for late phase and commercial clients with the completion of an extension to its facility in Carlsbad, California. Validation studies are currently underway and the first production batch is due to run before the end of the year, according to David Feldker, vice president SAFC Pharma.
The US$12m (Euro 8m) project includes the addition of two fully segregated viral product manufacturing suites, built to employ the latest in disposable bioreactor technologies, expanding SAFC Pharma's biologics, viral vaccines and gene therapy manufacturing to commercial-scale quantities.
SAFC Pharma's Carlsbad site specialises in the process development and manufacturing of viral vaccines and viral therapeutics, including a full menu of support services, from preclinical process and analytical development to final fill/finish and commercial bulk drug supplies. The new expansion, designed for multi-lot campaigns, includes dedicated cell expansion, bioreactor production, purification and cleanroom suites.
The addition of 8,000ft2 of manufacturing space to the existing 44,000ft2 site enables both 100-litre batch production in stirred tank bioreactors and 1,000-litre batch manufacturing in disposable bioreactors.
Disposable technology allows you to turn over rooms much more quickly," Feldker explained. "We are handling an infectious product so you really want to make sure it's completely out of the system and disposables can do that."
Designed from the outset as a containment facility, the expansion space is Biosafety Level 2 compliant, allowing manipulation of human pathogens, and allows clients to secure a dedicated suite of cleanrooms for larger scale manufacturing.
"We expect to see a great deal of value in the biologics and viral manufacturing marketplace in the next three to five years generated by two main customer types - those with late clinical phase opportunities but without any in-house manufacturing capability and those with late clinical phase opportunities that have some manufacturing capabilities but may be seeking an additional 'safety net' or wish to avoid additional capital expansion until their technology and drug has proven itself," said Feldker.
NCI sponsors 6th Reolysin study - Multiple Myeloma
http://www.integratir.com/newsrelease.asp?news=2131024824&ticker=T.ONC&lang=EN&ny=on
Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) announced today that the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, has agreed to sponsor a Phase I study of REOLYSIN® alone in patients with relapsed multiple myeloma. The NCI is sponsoring the trial under its Clinical Trials Agreement with Oncolytics, while Oncolytics will provide clinical supplies of REOLYSIN. The Principal Investigator is Dr. Craig Hofmeister of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
"While progression free survivals have improved with novel therapies over the last decade, the cure fraction remains low and additional options are needed," said Dr. Craig Hofmeister, principal investigator. "Multiple myeloma cells are frequently RAS activated, especially in relapse, so we are very interested in looking at REOLYSIN for these patients."
The study will initially be a proof of concept, open-label Phase I study of REOLYSIN in patients with relapsed multiple myeloma. Approximately 12 patients will receive REOLYSIN, in a dose escalation up to 3 x 1010 TCID50 per day administered intravenously on days one through five every 28 days.
The primary endpoint for the dose escalation portion of this study will be adverse events using CTCAE criteria. Correlative studies will focus on the efficiency with which reovirus replicates in patient myeloma cells. Investigators will use standard cohorts-of-three phase I dose escalation design with three to six patients being treated at each dose level. Secondary endpoints will include clinical benefit, duration of response, and time to progression.
This is the sixth clinical trial using REOLYSIN to be sponsored by the NCI. The NCI is currently conducting a Phase II metastatic melanoma trial, a Phase I/II and a randomized Phase II ovarian, peritoneal and fallopian tube cancer trials, a randomized Phase II trial in pancreatic cancer and a Phase I trial in pediatric patients with relapsed or refractory solid tumors.
About Myeloma
The American Cancer Society estimates that 20,180 Americans were diagnosed with myeloma and an estimated 10,650 Americans were expected to die from the disease in 2010. The prognosis for patients diagnosed with myeloma varies but the five-year survival rate for the period between 1999 and 2005 was approximately 37%.
About the NCI
The U.S. National Cancer Institute (NCI) is part of the National Institutes of Health and the U.S. Department of Health and Human Services. NCI's main responsibilities include coordinating the National Cancer Program; conducting and supporting cancer-related research; training physicians and scientists; and disseminating state-of-the-art information about cancer detection, diagnosis, treatment, prevention, control, palliative care, and survivorship.
About The Ohio State University Comprehensive Cancer Center
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Oncolytics featured on This Week in Virology TWIV
http://www.twiv.tv/
Oncolytics CEO Brad Thompson is this weeks guest talking about Reovirus and ONC/ONCY
TWiV 131: A REOstat for cancer
http://traffic.libsyn.com/twiv/TWiV131.mp3
Hosts: Vincent Racaniello, Alan Dove, Dickson Despommier, and Brad Thompson
Vincent, Alan, and Dickson chat with Brad Thompson, CEO of Oncolytics Biotech, about using reovirus to treat cancer.
ONCY at Needham Healthcare Conference April5th 10am
http://www.newswire.ca/en/releases/archive/March2011/31/c8064.html
CALGARY, March 31 /CNW/ - Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX: ONC) (NASDAQ: ONCY), will present a corporate overview of the Company at the 10th Annual Needham Healthcare Conference on Tuesday, April 5th, 2011 at 10:00 a.m. ET. The conference will take place on April 5th and 6th at the New York Palace Hotel in New York, NY.
A live audio link to the webcast presentation is available at:
http://www.wsw.com/webcast/needham44/oncy/ , or on the company's website at www.oncolyticsbiotech.com . It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
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.
Oncolytics Announces 2010 Year End Results
CALGARY, March 17 /CNW/ - Oncolytics Biotech Inc. (TSX:ONC, NASDAQ:ONCY) ("Oncolytics" or the "Company") today announced its financial results and operational highlights for the year ended December 31, 2010.
"2010 was marked by the further expansion of our late-stage clinical program, particularly with respect to the addition of randomized trials and new indications," said Dr. Brad Thompson, President and CEO of Oncolytics.
"Both during the year and subsequent to year end, we were able to significantly strengthen our balance sheet. This will allow us to further our goal of moving REOLYSIN® through the last steps of product development."
Selected Highlights
Since January 1, 2010 the Company has announced:
Clinical Trial Results
A poster presentation at the ASCO 2010 Annual Meeting, entitled "A Phase I/II study of oncolytic reovirus plus carboplatin/paclitaxel in patients with advanced solid cancers with emphasis on squamous cell carcinoma of the head and neck (SCCHN)," showing that of 19 head and neck cancer patients evaluable for response, eight (42%) had partial responses and six (32%) had stable disease; mean overall survival in 24 treated head and neck cancer patients was more than eight months;
Presentation of interim data from a U.K. translational clinical trial investigating intravenous administration of REOLYSIN® in patients with metastatic colorectal cancer prior to surgical resection of liver metastases. The researchers concluded that reovirus can be successfully delivered specifically to colorectal liver metastases following intravenous administration as a monotherapy and that pre-operative treatment was safe, suggesting that application of oncolytic viral therapy can be widened to the neoadjuvant setting;
Publication of a paper entitled "REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer," by Comins et al in the journal Clinical Cancer Research. The paper reported final results from a combination REOLYSIN and docetaxel trial designed to evaluate the anti-tumour effects of systemic administration of REOLYSIN in combination with docetaxel (Taxotere®) in patients with advanced cancers. A disease control rate (combined complete response, partial response and stable disease) of 88% was observed. The authors concluded that the combination of reovirus and docetaxel was safe, with evidence of objective disease response, and warrants further evaluation in a Phase II study;
Start of enrollment and preliminary results from a U.S. Phase 2 clinical trial (REO 017) using intravenous administration of REOLYSIN in combination with gemcitabine (Gemzar®) in patients with advanced pancreatic cancer. Seventeen evaluable patients with pancreatic cancer were expected to be treated in the first stage and if three or more patients received clinical benefit, the study would then proceed to the next stage. This endpoint was met after six evaluable patients were enrolled.
Ongoing Clinical Program
Approval from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to conduct a Phase 3 trial examining REOLYSIN in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers;
Receipt of a No Objection Letter from Health Canada to conduct its Phase 3 trial examining REOLYSIN in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers;
Receipt of approval from the Belgian Federal Agency for Medicines and Health Products (FAMHP) to conduct its Phase 3 trial examining REOLYSIN in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers;
Opening of enrollment in a Phase 3 trial examining REOLYSIN in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers;
The Cancer Therapy & Research Center at the University of Texas Health Science Center (CTRC) had started patient enrolment in a U.S. Phase 2 clinical trial using intravenous administration of REOLYSIN in combination with carboplatin and paclitaxel in patients with squamous cell carcinoma of the lungs (SCC lung cancer);
Completion of Phase 1 patient enrollment in a Phase 1/2 clinical trial to investigate the use of REOLYSIN for patients with recurrent malignant gliomas (REO 007);
The opening of enrollment in a U.S. Phase 1 study of REOLYSIN in combination with FOLFIRI (Folinic Acid (leucovorin) + Fluorouracil (5-FU) + Irinotecan) in patients with oxaliplatin refractory/intolerant Kras mutant colorectal cancer (REO 022);
Start of enrollment in a randomized Phase 2 trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN in patients with persistent or recurrent, ovarian, fallopian tube or primary peritoneal cancer to be conducted by the Gynecologic Oncology Group (GOG) and sponsored by The Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. NCI, which is part of the National Institutes of Health;
The Children's Oncology Group (COG) intent to conduct a Phase 1 trial of REOLYSIN in combination with cyclophosphamide in pediatric patients with relapsed or refractory solid tumors sponsored by the NCI;
Start of enrollment in a 2-Arm randomized Phase 2 study of carboplatin, paclitaxel plus REOLYSIN versus carboplatin and paclitaxel alone in the first line treatment of patients with recurrent or metastatic pancreatic cancer sponsored by the NCI;
Completion of enrollment in a U.K. translational clinical trial investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases (REO 013);
Intellectual Property
Grant of the Company's 35th U.S. Patent, No. 7,731,951 entitled "Viruses for the Treatment of Cellular Proliferative Disorders." The patent claims cover methods for treating cell proliferative disorders by administering modified vaccinia virus to proliferating cells having an activated Ras-pathway;
Grant of U.S. Patent, No. 7,803,385 entitled "Reoviruses Having Modified Sequences." This is a composition of matter patent that covers the reovirus variant the Company is using in its clinical trial program and expires in 2028;
The company now has 41 U.S. patents in total;
Financial
Completion of a bought deal financing issuing 5,440,000 units of the Company at a price of $4.60 per Unit for gross proceeds to the Company of approximately $28.77 million;
Pursuant to the acceleration of the expiry date of those warrants issued on November 23, 2009, the Company received proceeds of approximately US$6.8 million resulting from the exercise of 1,943,000 warrants; and
The exercise of 1,322,750 warrants, issued in connection with the financing that closed on November 8, 2010, providing the Company with proceeds of approximately $8.2 million.
Reovirus delivery using Dendritic Cells (DC)
Internalization of Oncolytic Reovirus by Human Dendritic Cell Carriers Protects the Virus from Neutralization
http://clincancerres.aacrjournals.org/content/early/2011/03/09/1078-0432.CCR-10-3266.abstract
Elizabeth J. Ilett1, Montserrat Barcena2, Fiona Errington-Mais1, Stephen Griffin1, Kevin J. Harrington3, Hardev S. Pandha4, Matthew Coffey5, Peter J. Selby6, Ronald W.A.L. Limpens2, Mieke Mommaas2, Rob C. Hoeben7, Richard G. Vile8, and Alan A. Melcher9,*
+ Author Affiliations
1Leeds Institute of Molecular Medicine, University of Leeds
2Dept of Molecular Cell Biology, Leiden University Medical Centre
3Targeted Therapy Team, The Institute of Cancer Research
4Oncology, Post Graduate Medical School, University of Surrey
5Oncology, Oncolytics Biotech Inc
6CRUK Clinical Centre, University of Leeds
7Molecular Cell Biology, Leiden University Medical Centre
8Molecular Medicine, Mayo Clinic
9Oncology Unit, St James's University Hospital
* Corresponding Author:
Alan A. Melcher, Oncology Unit, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, United Kingdom a.a.melcher@leeds.ac.uk
Abstract
Purpose: Dendritic cells may be the most effective way of delivering oncolytic viruses to patients. Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing anti-viral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility using a variety of cell types and viruses. This study addressed the efficacy of human dendritic cells (DC) to transport virus in the presence of human neutralizing serum.
Experimental Design: Following reovirus-loading, DC or T cells were co-cultured with melanoma cells ± neutralizing serum; the melanoma cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated using labelled tumour cells and the ability of reovirus-loaded DC to prime T cells was also investigated. Results: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for melanoma cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific anti-tumour immune responses.
Conclusions: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for metastatic disease with induction of an anti-tumour immune response.
Received December 10, 2010.
Revision received February 18, 2011.
Accepted February 25, 2011.
American Association for Cancer Research.
RBC Capital Markets Healthcare Conference Panel Discussion
Cancer Treatments: Under the Radar Unique Late Stage Opportunities - Oncolytics CEO Dr. Brad Thompson will be a panel member.
Starts now if anybody is interested
2011 RBC Capital Markets Healthcare Conference
http://irgnews.com/coi/ONCY/Oncolytics-Biotech-Inc-to-Present-at-RBC-Capital-Markets-Healthcare-Conference
The link is at
http://www.wsw.com/webcast/rbc129/rbc129.panel1/
Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX:ONC.to) (NASDAQ:ONCY), will participate in a panel discussion at the RBC Capital Markets Healthcare Conference on Wednesday, March 2nd, 2011 at 9:00 a.m. ET. The conference takes place at the New York Palace Hotel on March 2nd and 3rd, 2011.
A live audio link to the webcast presentation is available or is on the company's website. It is recommended that listeners log on 10 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus.
2011 RBC Capital Markets Healthcare Conference
http://irgnews.com/coi/ONCY/Oncolytics-Biotech-Inc-to-Present-at-RBC-Capital-Markets-Healthcare-Conference
The link to this eagerly anticipated webcast is at
http://www.wsw.com/webcast/rbc129/rbc129.panel1/
The webcast is tomorrow morning prior to market open... this will be a very interesting market open if ONC announces another randomized clinical trial.
Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX:ONC.to) (NASDAQ:ONCY), will participate in a panel discussion at the RBC Capital Markets Healthcare Conference on Wednesday, March 2nd, 2011 at 9:00 a.m. ET. The conference takes place at the New York Palace Hotel on March 2nd and 3rd, 2011.
A live audio link to the webcast presentation is available or is on the company's website. It is recommended that listeners log on 10 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus.
Oncolytics Receives $7.7 Million from Exercise of Warrants
After market surprise voluntary early exercise at approx $6.15(Can) per share and let me repeat the most important part of the release... "The Corporation plans to use the proceeds to fund an additional randomized clinical trial." Possibly announced at tomorrow's RBC Capital Markets Healthcare Conference - Cancer Treatments: Under the Radar Unique Late Stage Opportunities where CEO Dr. Brad Thompson will be a panel member?
Oncolytics Biotech Inc. ("Oncolytics" or the "Corporation") (TSX: ONC) (NASDAQ: ONCY) today announced that the Corporation's biggest institutional shareholder, has exercised 1,248,800 warrants, issued in connection with the financing that closed on November 8, 2010, providing the Corporation with proceeds of approximately $7.7 million. Oncolytics now has approximately 71.1 million shares issued and outstanding, and cash on hand and available for operations of approximately $55 million. The Corporation plans to use the proceeds to fund an additional randomized clinical trial.
The common shares underlying the warrants were offered in Canada by way of a prospectus supplement to a short-form base shelf prospectus dated June 10, 2010 that had been filed in the provinces of British Columbia, Alberta, Manitoba and Ontario. Copies of the prospectus supplement and accompanying base prospectus relating to the offering may be obtained from the SEDAR website www.sedar.com, or from the Corporation using the contact information provided below.
The securities issued by Oncolytics have not been and will not be registered under the United States Securities Act of 1933, as amended (the "1933 Act"), or the securities laws of any state of the United States, and may not be offered or sold in the United States or to, or for the account or benefit of, U.S. persons (as defined in Regulation S under the 1933 Act) unless registered under the 1933 Act and applicable securities laws of any state of the United States or pursuant to an exemption from such registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful.
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 human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Oncolytics Bio CEO & Investor Conference Transcript
This is not a full transcript, but only some parts that RJC found either new, or particularly interesting.
CEO Brad Thompson's presentation date: 2/14/2011
You can currently hear the webcast at:
http://www.veracast.com/webcasts/bio/ceoinvestor2011/61114431.cfm
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Miscellaneous H&N selections:
- We currently have 20 [Phase III H&N] centers enrolling right now, and should have between 45 and 50 centers enrolling by summertime.
- We anticipate being fully enrolled (in the full 280 patients), some time in calendar year 2012
- What we've powered this study for is looking at a maximum 10% response rate and a control arm median PFS of 2 months and we actually powered it for 2 different survivals … 4 1/2 months (which is what we expect, and 6 months survival. So if you look at that 200 patient outcome that is most likely in the second stage, it's actually powered against the 6 month potential survival and the control arm, which gives us quite a bit of latitude in case the patients do better, which they often do
- If we duplicate [the UK Phase II H&N results] in the Phase III, it could be statistically significant at 80 patients, but we'll continue to run patients under that Study even if they are, as it's not a large enough safety package.
Squamous Cell Carcinoma Lung
{11:25} The key thing looking at squamous cell is not so much tumor regression, but whether you're getting bleeding post tumor regression … which has been an issue with some of the other studies that have been done. So far we haven't seen that. Again, it's early days and while this is typical of what we're
seeing, I wouldn't want to predict necessarily that's typical in the end.
NSCLC Trial:
In the section starting at {12:25} where Brad says that "We're running a single arm Non-Small Cell Lung study, which should now report near mid-year.", he follows with the well chosen words that "… we're quite looking forward to getting this data out".
Texas Gemzar/Reo pancreatic
{13:20} We're looking at a single-arm study involving Reolysin in combination with current standard of care (which is Gemzar) … just to show you how low the bar is in this particular area. It's a "Simon two-stage" design, and we needed 3 or more Stable Diseases in the first 17 patients to proceed on to a second Study which could either be the same Study expanded, the same Study with the addition of a taxane, or a randomized Study. We're in the midst of thinking what exactly we want to do there. We met that end point and actually in 6 patients there was a Partial Response, 3 Stable Diseases by RECIST, a Stable Disease patient who was within his last 2 days of therapy to get to 12 weeks and he decided he wanted to go on to something else, and 1 Progressive Disease. So quite encouraging, even though early.
NCI Carbo/tax/Reovirus pancreatic
{14:09} The other Study that we're working on (which is starting up now), is an interesting randomized Study that the NCI is actually sponsoring (which is I suspect how they got FDA Approval to run a non-standard of care Study in First Line), where they're looking at carbo/tax in combination with Reolysin versus carbo/tax. It's a very very interesting Study given that it excludes Gemzar.
On pancreatic imaging
{14:50} The tumors are mostly normal tissue … 75-80% of the tumors are normal strata so it's very hard to see what's underneath. You could completely get rid of the tumors in some cases and still end up only having Stable Disease by RECIST, so it's a bit of a challenge and us and other people are trying to incorporate imaging to get to these end points but of course again you have to worry about the FDA and if they'll accept them with the PFS end-point or not.
Manufacturing
{17:30} We're currently producing at the 100 liter scale which produces over 100,000 IV doses, so a 100 liter facility is actually well comfortable for us to do a launch with. We're actually finishing off the final validation this year, then we're going to start stockpiling product in anticipation of launch.
Stock
{17:55} Our trading volumes are about 55% NASDAQ, 45% Toronto. We're about 40% institutionally held. Most of that is outside of the US. From a cash basis, our anticipated burn this year is between 2 and 2.2 million [per month], and lower next year actually as we finish Phase III enrollment, and so with the cash as of Jan 24, we had about 2 years of cash. We're just a little under 2 years right now. So this takes us past our data read-out on our Phase III Study, and allows us to finish up all the other Studies that we're conducting right now.
Summary
{18:35} Something to look forward to. Early Phase III data by year end, or early next year and we've got the other two randomized Studies that be finishing enrolling early next year and we continue to develop our IP portfolio and have leapt over the hurdle of manufacturing which for this particular biologic was a very important milestone.
Q&A
Question on partnering strategy …
{19:20} Given that we're not that far away from a first early Phase III data read-out … it's always been our intention to partner before we ran large registration studies in big indications. I can handle Head and Neck, but a large thousand patient registration Study in the other indications I think is
beyond our capability. We're pursuingpartnering. We're in active discussions with quite a few people, and I would expect however that we'll either partner very soon, or after the first part of the Phase III data comes out. There will be a peak and then a trough and then a peak again.
Unheard Question
{22:00) It'll be later this year that it will be done. It's a very specific subset, and as my colleague Dr Matt Coffey says "We don't want to rush to failure", and we want to make sure we get a pure patient population. It's really a function of the number of sites. If we're focusing our time and attention on getting site numbers up, and getting as broad a country representation as possible, we're probably 8 or 9 countries on by mid-year, and doubling and a half our current sites (which are around 20) … so we should have it done later this year. It's a very specific sub-patient type though. We're being very very particular about keeping the enrollment criteria narrow.
Survival for lung or pancreatic cancer
{22:00] Brad answers something like it's too early to tell, but then says "We're seeing responses we need, certainly higher than Gemzar alone." If you Inject locally will you get better responses
{22:50} You actually do on a tumor specific basis. We did local therapy when we started out for a variety of reasons, and you overcome delivery issues by doing it local. There's two things. There's the immune system between the injection site and the tumor, and then getting into the tumor, and both are issues
depending on which virus you're using. For us, the immune system isn't much of an issue, but certainly the tumor interface is an incredibly important issue, and that's where the taxanes and radiation really are key when we're using them together because they make the tumor's very porous or the virus will actually get through the tumor in the presence of those agents than it does without.
When we did intertumoral, we got very close to the theoretical response rates. We usually expect around 2/3 response rate and that's what we did on the tumors. We did see some tumor to tumor transmission of the virus. It's just in that particular case it takes it out of a general clinic use basis and turns it into
a surgical technique. A lot of tumors are just inaccessible. To do stereotactic delivery intertumorly, it's necessary [inaudible] of certain type so we've just gone the route of IV, but we needed to conquer those delivery issues.
If we hadn't, then intertumoral would be the better case. Needing to be aware of the issues is new for us as well. For the whole group of us that are working in virology, we didn't actually understand what the issues were until we got into the clinic, and I think we do now.
Immune Response question
{24:40} You have to have a time frame for an immune response to occur. With more aggressive tumors and with more aggressive metastatic disease, I think you need to lean towards something that's more of a cytotoxin than an immune response. I think that immune therapies will work in the First Line … I know they do … there are certain homes that are better for certain types of cancers, and with us working on these more aggressive ones, I think you need a cytotoxin.
With some of the slower ones, I think that immune therapy is a great approach, and we're seeing that in the clinic with other people's agents.
Thanks to rjc for the transcribing and posting the best parts.
Acuity now holds >10%+ of Oncolytics stock
It appears that Acuity Investment Management Inc. is declaring ownership of 7,222,100 shares of Oncolytics Biotech (10.33% of Oncolytics Biotech).
http://xml.10kwizard.com/filing_raw.php?repo=tenk&ipage=7395713
Acuity's holdings as of Dec 31, 2010 are 100% Canadian, and total $119 million.
Acuity is 100% owned by AGF Management Limited.
About AGF Management Limited:
Founded in 1957, AGF Management Limited is a premier Canadian-based investment solutions firm with industry-leading financial performance, talent and clients relationships. To serve the needs of a broad range of diversified clients worldwide, the firm consists of two distinct businesses: AGF Investments and AGF Trust.
AGF has $43 billion of assets under management as of Dec 31, 2010
Thanks rjc for digging this up
PII Pancreatic Trial Meets Endpoint at 6 patients
The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center.
These preliminary results are from Part A of a combo study in combination with Gemzar for advanced pancreatic adenocarcinoma. The clinicaltrials.gov link for this trial is here:
http://clinicaltrials.gov/ct2/show/NCT00998322?term=reolysin&rank=6&flds=Xabcfghjklopqst
"Seventeen evaluable patients with pancreatic cancer were expected to be treated in the first stage and if three or more patients received clinical benefit, the study would then proceed to the next stage. This endpoint was met after six evaluable patients were enrolled. All patients treated reported symptomatic improvement.
Three of six patients showed SD for 12 weeks or greater. In addition, one patient had stable disease at nine weeks of treatment, but was taken off of the study for alternative treatment, and one patient had a PR of less than 12 weeks duration, and then died from a medical issue unrelated to treatment. The Company now intends to complete enrollment in the first stage of the study and then continue with further studies."
"Pancreatic cancer remains one of the most lethal cancers, ranking as the fourth leading cause of cancer death for both men and women. The American Cancer Society estimates that 37,170 men and women (18,830 men and 18,340 women) will be diagnosed with pancreatic cancer and 33,370 men and women will die of pancreatic cancer in 2008.
Activating KRAS mutations are the most frequent genetic abnormalities in pancreatic cancer (occurring in 75% to 95% of patients).
REOLYSIN has been demonstrated to kill a wide variety of cells with mutations along the RAS pathway, including pancreatic cancer cells.
The Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN given intravenously in combination with gemcitabine every 3 weeks in patients with advanced pancreatic cancer.
Response is a primary endpoint of this trial. Tumors will be evaluated by CT scan within 14 days of starting treatment, then at 6 weeks, and then every 6 weeks thereafter.
The safety of the gemcitabine and REOLYSIN combination will be assessed by the evaluation of the type, frequency and severity of adverse events, changes in clinical laboratory tests, immunogenicity and physical examination.
Patients may continue to receive therapy under this protocol, provided he/she has not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction."
The new randomized Phase II started recently by the NCI is with the Carbo/Tax combo so ONCY is now testing both combinations.
That trial link is at:
http://clinicaltrials.gov/ct2/show/NCT01280058?term=reolysin&rank=11&flds=Xabcfghjklopqst
Pediatric Oncolytic Virotherapy Conference Jan 25,2011
Thanks to taltell for the info... Reolysin featured as one of the therapies- DR. Adrus Kolb at 1 hr 6 minutes to about 1hr 16 minutes.
http://vimeo.com/20002455
An overview and discussion for parents and researchers of 5 new investigational agents in clinical trials for 2011 presented by the Principal Investigators.
New treatment options are needed for children with deadly solid and CNS tumors. A new class of investigational agents called Oncolytic Viruses became available to children in 2010, and in 2011 there will be five different clinical trials open offering various virotherapy agents.
Four distinguished Principal Investigators explain each virus therapy and answered viewers' questions.
This online parent/researcher forum was a live presenatation that covered:
* history of cancer virotherapy
* recent progress
* toxicity & efficacy
* myths dispelled
* specifics of each clinical trial
Solving Kids' Cancer supports effective, low-toxicity treatments for children with deadly tumors, and we are very excited about the work of these dedicated physicians and scientists who champion this same critical purpose.