Intercept Pharmaceuticals is a company on the brink of transformation. After establishing themselves as a leading R&D focused organization specializing in progressive non-viral liver diseases, Intercept is now turning its focus towards becoming a fully-integrated commercial biopharma with a global presence. It comes as little surprise, then, that the heart of their Canadian organization is based in Ontario’s leading city for the life sciences, Mississauga.
Brian Canestraro, general manager of Intercept Pharma Canada Inc., has been with the company since the creation of its Canadian affiliate in June 2015. Since then, he has overseen the establishment of Intercept’s Canadian headquarters and watched the company grow to become a global player in the life sciences.
“The importance of being able to help people, and being in an environment where you constantly have to innovate, has been very interesting to me,” says Canestraro.
Fighting a ‘crisis in the making’
In the realm of non-viral diseases of the liver specifically, the need for innovation is becoming an urgent one: a study released by the Canadian Liver Foundation in March 2016 suggested that 1 in 4 Canadians will be affected by liver disease.
“The Canadian Liver Foundation released a publication in 2013 that characterized liver disease as a ‘crisis in the making’,” he explains. “At that point in time, the Canadian Liver Foundation made a reference that in the previous eight years they saw an increase of liver related mortality by about 30 per cent.”
Alongside this urgency, Canestraro recognized the great potential for change.
“We are motivated by the opportunity to work with the Canadian liver disease community to make a meaningful difference in the area of liver disease, specifically non-viral liver diseases. Having the potential to impact the lives of one in four Canadians, is very rewarding,” he says.
With leading researchers and scientists, Intercept is working towards making that possibility a reality.
Intercept’s most advanced research and development programs focus on three progressive non-viral liver diseases: Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Non-Alcoholic Steatohepatitis (NASH).
“[These] are different types of progressive non-viral liver diseases that have significant unmet medical need,” he explains. “Diseases where either no approved therapies exist, as is the case for PSC and NASH, to diseases where new innovation hasn’t existed in over 20 years in the case of PBC.”
PBC and PSC are autoimmune liver diseases that see a person’s immune system attack the liver, causing progressive damage to the bile ducts. When the bile ducts are damaged, bile and other substances cannot be eliminated and accumulate in the liver. The retained substances are harmful to the liver and worsen inflammation which leads to further damage.
“Over time, this can result in the scarring of the liver and progression to cirrhosis, and for a number patients, the need for a liver transplant,” he says.
PBC, which affects the small bile ducts, impacts approximately 9,000 Canadians, the majority of which are women between the ages of 40 to 60. PSC, coined as the “brother disease”, is less prevalent and affects primarily men between the ages of 30 to 50.
NASH, conversely, is more widespread among Canadians. Believed to impact 2 to 6 per cent of the general population, NASH is a progressive chronic liver disease caused by inflammation of the fatty liver.
“It represents the more severe end of the spectrum of non-alcoholic fatty liver disease,” says Canestraro.
NASH can have devastating effects on the human body. Up to 20 per cent of adults diagnosed will develop cirrhosis, while up to 11 per cent may die from liver-related deaths.
By 2020, U.S. research suggests that NASH will represent the leading cause for liver transplantation.
A new way of thinking
Enter Obeticholic acid (OCA), an FXR agonist that Intercept has developed to treat liver disease. Obeticholic acid (OCA) is an investigational drug that is currently undergoing Priority Review with Health Canada for the treatment of Primary Biliary Cholangitis, when used in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. As of publication, Obeticholic acid (OCA) has not received market authorization from Health Canada, EMA, or any other regulatory body outside the U.S. As such, no conclusions can be drawn concerning safety or efficacy of OCA in indications other than PBC, or in areas outside the U.S.
“Historically, bile acids were thought of simply as ‘detergents’ that play a role in digestion by facilitating the absorption of dietary lipids and nutrients,” Canestraro says.
In the late 1990s, this thinking began to shift.
“Around the turn of the century, researchers uncovered a more complex role for bile acids, and so we now actually think of bile acids as acting cell signaling agents that bind to dedicated receptors. These essentially regulate liver, intestinal and kidney functions.”
It’s exactly the kind of innovation Canestraro has come to associate with the non-viral liver disease community, adding that OCA has the potential to become a “pipeline in a product” for multiple progressive, non-viral liver diseases including PBC, PSC, NASH and biliary atresia.
For Intercept, OCA is just the beginning. The company is currently overseeing PBC studies in seven liver disease centers across Canada and ongoing NASH studies in 11 different centers. This amount of research requires a wealth of talent – and for Intercept, there’s no shortage.
“Importantly, we have a growing team of industry experts on staff, and these are people who have expertise in the areas of Medical, Government, and Regulatory Affairs who have been working to support our Health Canada New Drug Submission and reimbursement activities,” Canestraro says.
These insights, from a functionality perspective, allow Intercept to keep up with a constantly evolving medical environment.
“Being in Mississauga, and being located centrally, has allowed us to tap into top-level pharma talent and support our growth because of the existing biopharma ecosystem and presence of other global biopharmas in the area.”
This growth is particularly important when considering Intercept’s plans for the coming years.
“More recently, we began planning out for commercial activities and the hiring of additional employees across the country to support our hopeful launch in the first half of 2017,” Canestraro says.
If Health Canada does approve OCA in 2017, he anticipates that Intercept will have the potential to go forward as a global biopharma player.
“I would like to see us successfully launch OCA for the PBC indication and bring what will be the first new treatment in over 20 years to Canadian PBC patients who remain at risk of disease progression despite treatment with the current standard of care,” Canestraro says.
Starting in a city of regeneration
Ever since basing its Canadian headquarters in Mississauga, Intercept has been become perfectly poised to expand business while supporting current operations.
“We specifically selected the Mississauga City Center for our Canadian location because of the fit with our broader corporate theme of ‘Regeneration’,” says Canestraro. “We viewed the current redevelopment of the Mississauga City Center to be consistent with this theme, while providing our employees with a motivating work environment and access to a number of amenities.”
“The transit system is also very convenient,” he says. “For our employees, it’s easy to get to Mississauga, and while they’re at work they can also go and accomplish a lot of other things with their free time.”
Laughing, he adds: “I think they do enjoy having access to all the shopping.”
As for himself, Canestraro says it’s been a valuable journey since the beginning.
“In June of 2015, it was myself and a cup of coffee in my home office,” he recalls. “Today, we are 17 employees across the country and getting ready for our first launch. It’s been a very interesting year and a half, to say the least.”