Oncolytics Biotech working to uncover a cancer killer

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By Shawn Lawrence

For decades scientists, researchers and even big pharma companies have all tried in vain to find the cure for cancer. While the concept of a magic bullet to beat the disease has long been abandoned, one company may have in fact uncovered a promising new treatment through the use of something that most people actually go out of their way to avoid: a virus.

While it sounds almost too good to be true or somewhat irregular, Oncolytics Biotech platform technology REOLYSIN® is exactly what its name implies, a virus or more specifically a reovirus.

Describing how it works, Oncolytics president and CEO Brad Thompson says the concept behind REOLYSIN® is that as a reovirus, it can enter all cells, but can only multiply with an activated Ras signaling pathway present, meaning the virus cannot multiply in normal cells. However in cancer cells with an activated Ras signaling pathway, the reovirus exploits the Ras activation to multiply within these cells, eventually killing them.

“Since approximately two thirds of all human cancer cells may have mutations along the Ras pathway, this means that two-thirds of all cancers could become targets for our REOLYSIN® therapy,” said Thompson.

According to Thompson it can be delivered systemically to patients with advanced cancers and cause anti-tumour activity. While the side effects of the treatment are headache, stomachache, fever and chills the tradeoff is immeasurable.

“Because it is non-pathogenic it does not cause disease in humans, meaning people shouldn’t be threatened that it’s a virus, and the fact it’s self replicating also presents all sorts of advantages to it. There’s probably around five million patients a year in the western world and in the middle-upper classes of the developing world that have come down with cancers that are due to Ras. Which means there’s a very large market opportunity for a drug like this.”

While the concept is new, the theory is quite old, but up until recently researchers weren’t able to validate the belief that viruses might in fact cause cancer to regress despite reports in medical literature going back to the 1880’s where people with terminal cancer came down with a new like illness and miraculously became cured. Explains Thompson; the explosion of genetics enabled the possibilities for companies such as ours to be able to validate this belief.

“So it was an old idea that required a bunch of new technology to be enabled.”
Thompson also believes there are very few cancer therapeutics under development that have the potential to treat as many cancers as this one.

The product itself was developed initially from the work of three University of Calgary lab researchers who discovered its effectiveness against cancer in 1999. Their findings indicated that the reovirus was able to kill cancer cells as long as a particular pathway was activated. They watched in amazement during the initial test as the reovirus successfully infected malignant tumours and replicating itself until the cancer was gone.

It wasn’t long after that they enlisted the help of Thompson, who was working elsewhere in the province as president and CEO of Synsorb Biotech Inc. Through a mutual correspondence in the Alberta government, Thompson got word of the findings of the three scientists and their “interesting and slightly different technology.”

The researchers, Patrick Lee (whose laboratory much of the reovirus work was done in), Matt Coffey and Tim Strong came to see Thompson shortly thereafter. During their discussions they talked about the possibilities of starting a business and to get some advice on what to do next to take their product to market. As the researchers presented hours worth of animal data, Thompson listened attentively to all the details about the Respiratory Enteric Orphan virus that the three men had developed. He could hardly contain his excitement at the potential of the technology as he heard how it could infect and selectively kill cancer cells with an activated Ras pathway. The technology astounded him.

“It was just one of those projects that just captured your imagination the first time you heard it. It was surprising to me really because university projects don’t normally have the type of depth nor are they that far advanced as what these men had.”

Realizing the potential of the product Thompson opted to leave Synsorb Biotech Inc. and within six months Oncolytics Biotech Inc. was born with Thompson taking on the role of CEO and president.

“What you had was three people who realized that they wanted to get a company out of this and that they needed to do a number of things. They were astute enough to file the original patent before they published and also to realize they were better off dealing with somebody who had actually done this before. That’s a very unusual circumstance with respect to a university group seeking to start a company. They brought the science and the technology and I brought the know-how to build the company.”

In taking on the role, Thompson accepted a dollar a month salary, which he said was very interesting to his family, yet it was one of those projects that he felt had to be done and is a move he has not regretted.
There were of course other reasons Thompson warmed up to the idea of Oncolytics. His connection to the disease the three men were targeting was definitely a major factor, he says.

“Until late 1998, early 1999, I didn’t really have much of a personal interest in oncology or pay much attention to it. But in a very short space of a few months I developed a pretty heightened personal awareness of the disease. My mom died of lung cancer, my uncle not long after of esophageal cancer and then I got my phone call.”

It was the phone call to tell him he had cancer, more specifically, melanoma.
“It was an interesting convergence, life altering really the genesis that took me where I am today. There I was then, just somebody who had been jarred out of thinking about bacteria infections to having a complete focus, almost obsessive on cancer. Then having people come through my door with a really interesting technology, saying they’ve got a virus that targets the disease, you can say I had a predisposition to jump on board.”

Now almost eight years later the company itself is on a roll as Oncolytics has seen encouraging signs in its clinical trials, with more than 130 patients treated in clinical studies to date. The company also initiated its REOLYSIN® Phase II clinical program in the U.S. and the U.K. last year, and further expanded this clinical program this year. In all, Thompson expects about eight Phase II studies to be conducted simultaneously, mainly immunotherapy studies in sarcoma, melanoma, brain cancer and ovarian cancer by the end of this year.

“What we’ve chosen to do is focus our time and energies on this one product and to do many clinical studies in parallel on that same product. It’s a much more big pharma approach to clinical development of a product in that pharma tends to explore the uses of a product much more broadly in its early stages and that tends to lead to a higher chance of success, more shots on goal early on. I believe this will really help us find what cancers it works best on in humans before we go into pivotal studies.”

As for the costs of doing things this way, Thompson says it’s actually not as expensive as one would think.

“In all we’re probably going to be enrolling nearly 200 patients in the next year and at $25,000 on average per a patient, you’re looking at maybe $5 million in clinical cost which is extremely modest. At our current burn rate we should average about $1.5 million a month to the end of next year, and under that we will have cash till at least 2009 with our expected burn rate.”

Results from those studies are expected in late-2007 and early 2008, leaving the company with sufficient breathing room in terms of its finances.

In terms of obstacles there have been a few says Thompson, among them is the higher standard Oncolytics has been held to by the regulatory agencies to demonstrate the safety of the product in early testing because REOLYSIN® is a virus.

“Things began slower than what you would particularly expect in the early stage with an agent. Really if we took the name REOLYSIN® off our product and called it compound X, I anticipate that it would have gone faster. But in the end I think we actually benefited from it because we’re moving forward with a much bigger data set than companies normally do at this stage and so that gives us a more robust belief in what we know about our product.”

And for Thompson, this is the most important aspect to drug is the fact the data shows its efficacy.

“It proves that this is not just a leap of faith, more so it reveals the strength of REOLYSIN® in the long-term. Unfortunately it’s also led to some minor problems in the short term.”

What Thompson means by problems is that because REOLYSIN® appears to be active against anywhere between 65% and 75% of any particular cancer it makes it difficult for the company to be able to decide what two pivotal studies it will go into for product registration. For now though, with Oncolytics in Phase II studies and trials moving along a lot more sprightly, Thompson doesn’t wake up at night worrying anymore whether the science will be accepted or approved by regulatory agencies. Instead his worries are more business oriented. Of particular concern are the day-to-day functions of operating a biotech company in Canada.

“In Canada, biotech companies tend to go public much earlier than our American and European brethren do. As a result we’re in the public environment at the very early stages of development, which happen to also be the longest stages where there’s not a lot of progress. There is some, but just not in the measurements shareholders are looking for. So this is one of the biggest challenges for me personally being a CEO in Canada, combating this shareholder fatigue. As such, I worry about such things as can we manage the growth of the company, can we manage the transition of shareholder-based problems now that we are more mature. More or less my concerns now are more business concerns rather than science and technology concerns.”

To overcome this obstacle, Thompson has positioned the company well in other areas.

“We started out in Canada doing first three small studies and then transitioned to the UK and the United States. It was a deliberate move. Canada is a very tiny portion in the world of oncology sales, very different in terms of portions you’d find in other drugs. Roughly 60% of oncology sales are in the United States, so our strategy is to run our clinical studies in the US and Europe because these are the two biggest markets in the world for oncology sale.”

The move is a means of looking ahead to getting product approval in the biggest market. For Thompson it’s the path of least resistance with getting approval from the FDA in the U.S., and the MHRA in the U.K.

“The Canadian studies really got us going but if you’re looking towards to serving the biggest markets you have to be running studies in those markets. It’s a big thing, I mean American patients treated by American doctors is what the FDA wants and in the U.K. they want English patients treated by English doctors, and that’s just the way it is.”

Aside from that, Thompson predicts his biggest obstacle is just around the corner, approximately six months from now when all the data starts to come in.
“We’re going to have an embarrassment of riches when it comes to data, and unlike most companies working in Phase II trials that know what they’re doing their pivotal study in for final product registration, we won’t know. And I can almost hear the arguments now because everybody has a pet cancer they’re interested in and if the data is relatively equivalent it’s going to be a very difficult task picking what we do next.”