Creating a Commercialization Engine for Molecular Diagnostics

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By Jon Yaneff

Like snow flakes, no two people in the world are exactly alike with the same genetic makeup.

That analogy perfectly describes ArcticDx Inc.’s uniqueness.
That uniqueness is defined through the hard work by the management’s determination as its team at ArcticDx creates a commercialization engine for molecular diagnostics within Canada.

There are many points that solidify this company’s uniqueness from the timeline of its inception of September 2005, where it was relatively inactive, until 2007 as things now start to make news all around the molecular diagnostics world.

The private Canadian company originated as a ‘spin out’ from the ARCTIC genome project, which was led by Cancer Care Ontario, McGill University and the Ontario Institute for Cancer Research. The ARCTIC project was the result of a four-year, $10 million research grant given to the principle investigators for the Genome Canada research program, Dr. Brent Zanke and Dr. Tom Hudson, who is a senior researcher at the Ontario Institute for Cancer Research. The ARCTIC project acronym stands for “Assessment of Risk in Colorectal Tumours in Canada.”

The research project led to about 16,000 patients within a multi-centre controlled study over three years with genome wide scans for polymorphisms (SNP’s) in five countries, including the United States, Scotland and France. In each of those five studies there was a controlled study with more then 1,000 patients. The statistical significance achieved in those findings gave very high statistical relevance with extremely powerful P values.

Dr. Zanke and Dr. Hudson’s work together eventually generated some significant discoveries with respect to genetic markers around colorectal cancer and led to ArcticDx’s first patent holding, but they had to negotiate the rights for all the intellectual property that came from the ARCTIC project with Cancer Care Ontario, which owned all of the patents on genes related to colorectal cancer. All of Zanke and Hudson’s discoveries and Cancer Care Ontario then formed a legal agreement with ArcticDx and the intellectual property and the rights of those markers were licensed to company founder Dr. Zanke, who is now the chairman and chief medical officer of ArcticDx.

This March, Dr. Zanke approached Greg Hines, current president and CEO of ArcticDx, who had just sold his Canadian molecular diagnostics company, Tm Bioscience, to Luminex Corporation. Hines then brought his management team, consisting of chief financial officer James Pelot, V.P. of regulatory affairs Alan Coley and the V.P. of marketing Stephen Weiss, along with himself to help run ArcticDx with Dr. Zanke.

“What my management team and I learned at our last company (Tm Bioscience), that took 12 genetic tests through design and development into the market place, was that even though there was a lot of work and money being spent around the Human Genome Project when trying to discover genetic markers, there was very little in the way of genetic markers that have actually come through as diagnostic tests,” said Hines. “In other words it is seven years removed from the Human Genome Project inception in 2000 and we don’t really know what the genetic link is for all of the major diseases. There was a lot of promise that there was going to be major health care discoveries, new drugs and new diagnostic products, but there aren’t a lot of them and the rationale is that science is proving more difficult than what was originally thought.”

Since the former Tm Bioscience core transformed into ArcticDx, a prestige honour proceeded to hit the ArcticDx brass when ARCTIC researchers published genetic sites determining colon cancer risk in the influential genetics journal, Nature Genetics, on July 8.

“Subsequent to that publication ArcticDx received a mass amount of media coverage,” proclaims Hines. “We had over 880 media hits, including The Toronto Star giving us full-page coverage, a quarter-page from the Globe and Mail and we were on CTV’s 11 p.m. news broadcast.”
On that same day Nature Genetics published the results of similar genetic research relating to colorectal cancer that was done at Harvard University and another group of researchers from Cancer Research UK (CRUK) in London, England.

“What’s unique about that is there were three separate groups studying the same thing, they all found the same result and were all published on the same day in one of the most peer review journals in the world,” said Hines. “We didn’t know they were researching the same thing, but the significance of that is that pretty much proves the markers we discovered are clinically proven. What’s also distinctive about that is we believe we filed the intellectual property on those markers the year before, so even though we all discovered the finding at the same time, we own the commercial rights. Those researchers however didn’t do the research to make a commercial product; they did the work to solely make the discovery, as well as the publication.”

“What I think we’re doing with our company is taking academic bindings in genetics and with our commercialization process we are turning those university-based academic discoveries into something that doctors and their patients can actually use, because so many discoveries don’t make it to market. With our commercialization engine for genetic testing, we became the first company in the world to get a DNA diagnostic test approved by the Food and Drug Administration (FDA). We are in the process right now of signing a major strategic alliance with a university medical lab in Ontario (asked to remain anonymous) and we will train that laboratory how to build a molecular and genetic test, so that we can get genetic discoveries coming out of the university through a lab process that meets the FDA requirements.”

Companies that want to look at genetic markers for colorectal cancer will have to answer three questions: What is the strength of the patent? Is the science good enough to be FDA approved? And finally, what is the commercial viability? Universities have a technology transfer officer that usually tries to out license intellectual property or patents and the only question they can answer is in respect to the patent because they filed the patent, but they don’t know if it will go through the FDA or the commercial viability of the discovery. That’s why ArcticDx is partnering with the university.

ArcticDx products identify disease predisposition as a first step toward personalized health care. They do this through the Colo-Risk™ and the Macula-Risk™, which help predict colorectal cancer and age-related macular cancer respectively.

Right now about 6% of the population eventually gets colorectal cancer, so this year the provincial government in Ontario has devoted $193 million to be spent on screening colorectal cancer.

There are two different screening programs in place for colorectal cancer that are usually implemented for people over 50 years of age, which are the somewhat inaccurate FOBT (fico occult blood test) or the extremely invasive colonoscopy.

A FOBT is where a patient’s fesses sample is taken, sent to the laboratory and blood is then tested in the stool sample. Obviously not many people are comfortable with the procedure and only 10-20% usually complies. The test just informs you there’s blood in your stools, therefore it becomes inaccurately positive when red meat is detected in your system.

It makes sense then that the test that is more commonly used is the colonoscopy, which inserts a five-foot colonoscopy tube in the rectum to provide a visualization of the colon and requires a lot of prep work with complications for the patient, including taking a day-off, some anesthesia for the pain and it’s very expensive, but extremely accurate to detect and again only 10-20% show up for the test.

“Our Colo-Risk™ test is a genetic test can be done from a blood sample or a mouth swab, so it’s completely non-invasive if only the mouth swab is used,” said Hines. “We test the patients’ DNA to determine if the patient has a high risk factor for getting colorectal cancer, so since there’s about 6% of the population with the risk of getting colorectal cancer and once people hit 50 they should be going for a colonoscopy every two years. The Colo-Risk™ would apply by identifying individuals that are at risk of getting colorectal cancer and making sure they comply and show up for their colonoscopy. So if 10-20% of the population usually show up for their colonoscopy, let’s make sure it’s the right 10-20% because 20,000 people in Canada are diagnosed with colorectal cancer every year with the majority of them dying.”

Colo-Risk™ is the first product of its kind that can predict an individual’s risk of developing colorectal cancer and is expected to be available as a university hospital based testing service in 2008.

Hines said for all of the legal agreements to be in place with the Ontario university laboratory, all its initial funding will be in place and its first test for Colo-Risk™ designed, with all that design work done within FDA specifications by the targeted date of Dec. 31.

“In the first quarter of next year we will do all of our FDA required validation studies at the university hospital lab where those discoveries will build into a diagnostic test, then in the second quarter we will assimilate all of the data from the first quarter then prepare a submission for FDA approval and by the third quarter we will actually launch that test through the university medical laboratory and on the market.”

Macula-Risk™ is about three months behind each step and at the end of September ArcticDx acquired the international licensing rights of the significant markers for the diagnostics to age-related macular degeneration (AMD) from the University of Michigan.

“All of the markers for the Macula-Risk have been tested on nearly 25,000 patients before the commercial design is finalized, whereas most discoveries of this type are tested on 2,000 or 3,000 patients before the commercialization is implemented,” explains Hines.

About 10% of people over the age of 70 start to lose their eye-sight and this is a major genetic component.

“My mother is blind in one eye and half-blind in the other, so the question is did I inherit those same genes from my mom or did I attain my father’s eye genes,” said Hines. “If drugs and treatments can detect my eye sight starting to go early, I could therefore prevent it from happening. So we built a diagnostic test, the Macula-Risk™, to be able to screen people that have a family history of age-related blindness, identify those people that have that genetic prepotency to that disease and then train and educate them, so when they start to feel a bit of fuzziness in their eye sight they should immediately go to the hospital or their physician.”

Macula-Risk™ is ideal for mass screening of population to identify individuals suitable for at home education and surveillance programs as well as routine screening at appropriate intervals. New medicines for AMD treatment are continuously entering the market, but while they may prevent the development of the disease they don’t reverse the damaged regions of the eye and Macula-Risk’s early detection of the disease will improve patient outcomes.

With ArctixDx products developing down a properly driven road, reception of the company has been extremely supportive, with the strategic partnership with the Ontario university hospital as well as maintaining support through the Ontario government and the Ontario Institute for Cancer Research, this means there are zero negatives associated with the company, as Hines points out.

“I tend to be an optimist and that’s why I’m in the bioscience business as most of us are, to add value that is a positive result for the population. I think the attitude towards what we’re trying to do has been really positive.”