In the Right Spot

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By Deborah Komlos

Academic institutions, rich in expertise and associated infrastructure, are often the progenitors of biotech firms. These spinoffs typically maintain close ties to their parent sites, and in the case of Vancouver, B.C.-based OncoGenex Technologies Inc., staying put has reaped its own rewards.

Dr. Martin Gleave, founder and CSO of OncoGenex, strongly praises the facility where his firm was established. Housed in the Prostate Centre of Vancouver General Hospital (Vancouver, BC), OncoGenex is surrounded by the centre’s team of close to 70 people, including 12 transdisciplinary scientists spanning a spectrum of translational research areas such as molecular and tumour biologists, experimental pharmacologists and clinicians. The hospital itself is the primary patient care, teaching and research hospital in British Columbia and is an affiliate of the University of British Columbia (UBC) (Vancouver, BC), from which OncoGenex was spun off in 2000.

With the specific aim to design targeted cancer therapeutics that inhibit tumour cell adaptation, OncoGenex has a team of five full-time staff, including Gleave, who also holds the positions of professor in UBC’s department of Surgery and director of Basic Science Research in that department’s division of Urology, practicing surgeon, and director of Clinical Research at the Prostate Centre, among others.

“We identify gene targets and produce targeted therapies in the laboratory that are then patented through UBC and spun off or licensed off into OncoGenex, and OncoGenex is the commercial vehicle, so to speak, of our translational research program,” Gleave says of his firm’s role.

He explains that translational research is a “bench-to-bedside process, whereby new discoveries are seamlessly carried forth into human testing.”

Thanks to the productive and skilled academic milieu in which OncoGenex is situated, the firm’s research program is very focused and goal-oriented, he says, and as a result it is able to plan for an accelerated transition from laboratory to end product. “It’s a win-win-win situation; it’s good for the company, it’s good for our lab, it’s good for the university,” Gleave says.

Strategic Paths

But such progress cannot be made without first having a formalized plan for the marketplace, Gleave cautions. And that is where OncoGenex has stepped in.

“The business model of OncoGenex was to stay quite virtual and to leverage off a huge infrastructure at the Prostate Centre and the Prostate Centre’s network,” Gleave says. “One of the many problems is that many biotech companies try to reproduce the research environment side of an academic environment, and that can be successful, but it also results in the demise of many because all their early cash goes into reproducing a very complex environment.”

Part of the firm’s philosophy, Gleave says, is to partner early. This was the case for its lead compound, OGX-011, which is being co-developed with Isis Pharmaceuticals Inc. (Carlsbad, CA), a move that Gleave says allowed OncoGenex to benefit from Isis’s significant structure and expertise in antisense chemistry, clinical development and preclinical platforms, all of which complemented OncoGenex’s expertise as well.

Remaining at the Prostate Centre and leveraging the advantages of infrastructure also created a beneficial financial circumstance, Gleave says.

“We’re probably the only biotech company to go from a discovery to a first-in-man clinical trial with a new agent for under a million dollars US,” he says. “From a burn point of view we kept it pretty small. We were able to do a lot of that through clinical trial grants and other research grants at the Prostate Centre.”

Gleave explains that OncoGenex’s research, which uses automated, miniaturized and high throughput robotic technology such as a microarray system, involves analysing tumours before and after treatment with hormone therapy or chemotherapy to identify genes that become activated in the process and are associated with cell death or treatment progression. These assessments are done using gain-of-function and loss-of-function tests. Antisense, he says, is one way to do the latter.

An antisense oligonucleotide, OGX-011 inhibits the production of clusterin, a protein that makes tumours in several cancers resistant to conventional treatments (e.g., chemotherapy, radiation therapy and hormone ablation therapy). The product is currently in two Phase I clinical trials, one for prostate cancer and the other for solid tumours. OncoGenex also has four other drug candidates in development, including OGX-225, a targeted therapeutic being developed to simultaneously inhibit the production of two proteins involved in tumour cell growth and the development of metastatic cancer.

An Academic Core

For Gleave, founding and helping to run a biotechnology company has not involved a drastic career change, but rather, was a necessary extension to facilitate the group’s research goal.

“It isn’t a big leap, I’m not jumping from a small laboratory in the university. I’m already a practising physician, I have my own incorporated practice — as a surgeon we have to run a small business,” Gleave says. In this regard, he says he is used to the concept of running a small business, although the scope is nowhere near that of running a biotech firm.

Necessary help to establish OncoGenex came, Gleave says, from UBC’s University-Industry Liaison Office, as well as from Scott Cormack, who served first as interim CEO and is currently president and full-time CEO. Eventually, recruiting the other seasoned management members helped strengthen the firm and build corporate credibility.

While becoming a businessman was never his intention, Gleave says he thinks like one sometimes and doesn’t consider academia and business as mutually exclusive paradigms.

“I first and foremost decided to stay an academic, whatever that word means. In the university, I’m a professor of surgery. I’m going to stay a practising surgeon and researcher,” Gleave says. “I can best help OncoGenex by doing that; if I leave that space and go full-time OncoGenex, OncoGenex loses its foundation and opportunity for leverage in that regard. There are a number of people I know who maintain their academic position as it leverages their academic position as well as their business situation.”

Breaking into Biotech

Not only is UBC Gleave’s current employer and business partner, it’s also his alma mater. He initially studied physical education there and also wrestled competitively, earning the accolade of being a national wrestling champion as well as UBC’s athlete of the year in 1983. His interest in sports injuries inspired a transition to study medicine, followed by a fascination with surgery and ultimately, urology, which Gleave describes as “the balance between medicine and surgical techniques.

“Once I got into urology, I became more interested in cancer, which is a big part of urology — prostate cancer, bladder cancer, kidney cancer, are three of the top 10 cancers,” he says.

Venturing into the business realm has been exciting, Gleave says, even though it’s a huge additional strain on his time.

“It brings you in contact with a whole other world of people, who think differently, have different approaches to problems. I’ve thoroughly enjoyed it,” he says. “It’s still synchronous with how I spend my research time, how I want to move our targets forward, because the company is intimately involved with clinical trials and that’s what I do anyway.”

Gleave’s active participation in clinical trials across Canada typically involves interacting with big pharma such as Aventis Pharma Inc. (Laval, QC) for use of its chemotherapy agent Taxotere® in the OGX-011 prostate cancer trial.

With four Phase II trials of OGX-011 planned for next year — two in prostate, one in lung and a third to be decided — and a Phase I trial for OGX-225, and having interest from and dialogue with big pharma, OncoGenex is in a progressive position, Gleave says.

Particularly advantageous, he adds, is that his firm’s therapeutic products are geared toward use in combination therapies, rather than competing with the market share of conventional treatments. “We’re actually augmenting them,” he says.

One of the most important things in forming a biotechnology firm is to protect IP up front, Gleave says, which can involve getting advice from the parent university or an independent source. “Don’t be afraid of partnering. Partnering brings synergy as long as it’s done appropriately, and so you have to be careful of who you partner with,” he adds.

Fundamental as well, Gleave says, is the passion for the work that drives an endeavour in the first place. “Make sure that the goals of your laboratory and the goals of the company research are parallel, because then you’re not struggling to decide which route to take,” he says.

Gleave also believes it’s critical to contribute to the growing evolution of biotechnology.

“I think it’s an important aspect that we write into all of our grants, that if Canada is going to be competitive in the world of biotechnology over the coming one to two decades, significant investment has to be made at all levels of health research in the country and academics have to have a facilitated track towards spinning off biotech and also becoming more aware of the challenges of such a transition,” he says.

Aside from market forces and other factors that are beyond one’s control, Gleave says no immediate thoughts spring to mind on what he hoped could have happened differently with OncoGenex. “It’s worked out very well,” he says.

“Go forward,” Gleave adamantly advises any biotech startup. “It’s an exciting opportunity and just look for areas of leverage, that’s what’s important. Don’t necessarily leave behind your academic life if possible. Identify areas where it can be used to facilitate partnering and leverage.”