Strategically wedged between the many lanes of the Trans-Canada Highway and Pierre Elliott Trudeau International Airport at the west end of the island of Montreal, the Saint-Laurent Campus of Technoparc Montréal is this city’s bid to establish a world-beating concentration of research-intensive industries. The land was set aside for this purpose in the late 1980s and addresses have steadily filled up with high tech enterprises big and small. The first international resident arrived in 1996, as the Swedish pharmaceutical firm Astra spent $330 million to build and develop an ambitious facility that would house nearly every aspect of the drug discovery process, from fundamental chemistry and biology to advanced testing on animals.
Within a few years Astra had merged with the British multinational Zeneca as giants of the global pharmaceutical industry began to grapple with the growing difficulties of finding new products to bring to market. Such mergers led to a surplus of research capacity and a subsequent trend to reduce the size of operations around the world. A number of the affected sites were in Montreal, including AstraZeneca’s in Technoparc Montréal, which shut its doors at the end of 2012.
A protein purification system used by researchers at Montreal’s NEOMED Institute. Photo credit: Paul Eifert
The story could easily have ended there, with a fully outfitted 12,500 square-metre building sitting empty on a piece of prime real estate. Today, however, the parking lot is full. About 200 people work in this building on various aspects of drug discovery or development — about a third more than AstraZeneca ever employed there. Several are former AstraZeneca staff members who took up the challenge of finding new ways of turning pharmaceutical prospects into marketable products.
That challenge has proved to be vexing for the major players in this field, who are sometimes portrayed as fat cats turning out drugs on billion-dollar budgets. The reality is somewhat harsher: these corporate giants have traditionally spent a great deal of time and money exploring the pharmaceutical potential of various compounds only to end, as the process usually does, in failure. A high failure rate is ultimately essential to the success of any kind of drug discovery — the better to avoid bringing an unsafe or ineffective drug to market — but the associated financial risks have become profound, which is why this corporate sector has worked so hard to reorganize and in some cases reinvent the way it does business.
AstraZeneca’s abandonment of its Montreal digs reflected just this kind of corporate realignment. And although that is no longer where the company directly engages in the grass roots search for new drugs, the building is home to more of this activity than ever before.
The driving force that has maintained this research momentum is the NEOMED Institute, a not-for-profit body that has brought public and private investors into the most fundamental biological and chemical aspects of the drug discovery process. The organization now oversees some $90 million worth of funding and in-kind contributions that include partnerships with universities, hospitals and major pharmaceutical firms, including AstraZeneca, Pfizer, Janssen and GlaxoSmithKline.
A compound purification system that employs liquid chromatography to prepare samples for more detailed analysis at Montreal’s NEOMED Institute. Photo credit: Paul Eifert
NEOMED’s business model is premised on bridging the often profound divide that separates the commercialization of new drugs from the basic scientific research that reveals the raw materials that make up those drugs. Although the organization’s website and printed literature are illustrated with images of famous bridges from around the world, the analogy is more than colourful rhetoric. The need to span this gap has become a priority critical to the survival of the pharmaceutical industry, which now enthusiastically supports external researchers who can share the risks of studying complex chemicals that may be able to work wonders within the even more complex human body.
As if that mandate weren’t daunting enough, NEOMED has also committed itself to building up the business and technology ecosystem that nurtures the top researchers it needs. In addition to housing the industrial expertise of its own staff, the building has also invited other businesses to set up shop under the same roof. These independent companies include small start-ups specializing in areas such as medicinal chemistry, biological testing and pharmacokinetics, as well as a law firm specializing in biotechnology and intellectual property. They likewise benefit from access to a corporate facility outfitted with everything from impressive boardrooms to an outstanding cafeteria.
The Quebec government was one of the prime movers behind the creation of NEOMED at the end of 2012, just as AstraZeneca was preparing to leave Technoparc Montréal. The company’s parting gift was the building and most of its installed equipment, which enabled the new organization to hit the ground running with a ready-made headquarters.
Even more importantly, AstraZeneca transferred ownership of some of its advanced research projects, thereby providing NEOMED with a similarly ready-made scientific agenda. Several of these projects are approaching the point of clinical testing, which might never have happened if no one had been there to continue the work.
Philippe Walker, NEOMED’s chief scientific officer, has a favourite example of the progress that has taken place: a compound that goes by the name NEO6860. It is what pharmaceutical researchers call an antagonist, which means that it stymies the normal operation of biochemical channels in the body to gain some medical advantage. In this case, NEO6860, which acts at the TRPV1 ion channel, interferes with one of the mechanisms that generate the painful symptoms of diseases such as osteoarthritis.
This ion channel is well known, but previous efforts to shut it down have met with unacceptably severe side effects, including an increase in body temperature and dangerous impairment of an individual’s ability to feel heat. Over the last decade, Walker says, AstraZeneca’s Montreal operation had been working on an entirely new approach based on selective blocking of the ion channel. “We found a compound that blocks only the capsaicin activation but doesn’t block pH or heat activation, unlike other compounds that were tested before,” he says, noting that these features should prevent side effects. (Capsaicin is the active ingredient in hot chili peppers.)
Walker’s own background illustrates the rich brain trust that now populates the robust infrastructure that NEOMED inherited. “The site is like a giant toolbox for us to advance programs,” he says.
Walker, who worked for AstraZeneca in Montreal from the early 1990s until 2012, once led the company’s worldwide neuroscience drug discovery efforts, overseeing about 650 researchers in Canada, Sweden and the United States. Among those researchers was Andrew Griffin, an AstraZeneca chemist who counts himself as being among the last handful of people still working in the building at the end of 2012. Griffin was part of the team that discovered NEO6860 and is excited to be seeing it through to what should be a commercial future.
Griffin appreciates Walker’s comparison of NEOMED to a multidisciplinary toolbox that can move the results of pure science toward the realm of applied clinical investigation. Nevertheless, he is fond of admitting some bias toward the value of his own discipline in overcoming the fundamental difficulties associated with any drug discovery project. “This process fails for a number of different reasons,” Griffin says. “The biology of the human body may not accommodate what a new drug is supposed to do; new approaches may prove to show no additional benefit compared to successful agents on the market doing the same thing; or there may be some problem with pharmacokinetics, or unwanted side effects. In many cases these issues come down to the molecule itself, meaning it’s the responsibility of the chemist who designs these molecules in the first place.”
Nuclear Magnetic Resonance scanning confirms the molecular structure of agents studied at Montreal’s NEOMED Institute. Photo credit: Paul Eifert
In this light, it should come as no surprise that the search for drugs comes with a high price tag. Griffin’s former boss at AstraZeneca, Bill Brown, still works just down the hall from him and echoes this assessment. “The easy stuff’s been done,” says Brown. “It’s getting harder to find drugs, to do science. The targets are more difficult, the chemistry is more difficult. It becomes more expensive and it’s a risky business to start with. And at the end of the day big pharma has stockholders to answer to.”
NEOMED has its own bills to pay, but its mission departs from the traditional business model. As opposed to a single corporate entity taking on all the risk to bring a new product to market, an investment shared by public and private sector partners reduces the cost of such risk. The building itself is home to a wide variety of firms, so the necessary help might be no more than a staircase away.
In this way NEOMED has provided hope to researchers looking for ways across that unwelcome expanse that separates their promising ideas and inventions from the rigid economics and regulations of the pharmaceutical marketplace. For example, although the organization’s AstraZeneca site originally specialized in work on pain relief, the launch of NEOMED soon attracted the attention of people working at a vaccine development site operated by GlaxoSmithKline in the nearby Montreal suburb of Laval, which was also slated for closure. The emerging collaboration has enabled that site to stay in business and NEOMED to expand its horizons. “Before that, NEOMED was only able to attack small-molecule drug discovery programs,” says Walker. “But with the expertise we get through that new interaction, we can now develop vaccines or potentially antibodies through our biology program.”
At the same time, Walker points out that NEOMED is not immune to the ruthless economics of drug development, which still consumes a lot of cash. Attracting private firms to put up some of that cash means cultivating a research environment that is more attractive than anything they could maintain for themselves. “You must have an indigenous innovation capability because that’s what’s going to drive business development,” says Walker. “Big companies will come to you because you’re doing things better, faster and in a more intelligent manner than other places.”