Fork in the Road

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By Amber Lepage-Monette

Navigating the various routes to commercialization can be tricky, when companies are faced with a multitude of approaches that may very well differ from year to year and product to product.

Should they find partners early on to take over clinical trials and commercialization? Should they keep a drug until a later stage of development before licensing it out? Or, should companies try to sell the products themselves?

Though some biotechs know right from the beginning what their strategy will be, for most, luck, circumstance and unforeseen events are what really call the shots.

Lucky Break

In the area of cancer therapeutics, several Canadian biotechs currently have products in late-stage clinical trials, and are contemplating what course they will navigate.

Mississauga, Ont.-based YM BioSciences Inc. has two cancer drugs — tesmilifene, a chemotherapy potentiator, and TheraCIM, a monoclonal antibody that targets the epidermal growth factor receptor — in or entering late-stage clinical trials. Tesmilifene is currently in Phase III, and TheraCIM is in a Phase II trial, with Phase III trials expected early this year.

Tesmilifene — which is paired with traditional chemotherapy treatments and targets MDR+ cells, or multiple drug resistant cells — has shown in clinical trials to be more effective for a subset of women with rapidly progressing breast cancer.

In tesmilifene’s first Phase III trial, a subset of patients with rapidly progressing breast cancer who were in the tesmilifene/chemotherapy combination group showed a median survival of 30 months compared to women on chemotherapy alone, who demonstrated a median survival of 12 months.

In the overall trial, median survival was 16 months in the chemotherapy alone group, and 24 months for the combination group.

When it comes to YM BioSciences’ overall corporate approach to product commercialization, ironically, neither of these two lead products fit into the typical plan.

“The instant we license a drug in we start thinking about who might want to buy it from us,” says YM chairman and CEO David Allan.

YM understands that sometimes plans unexpectedly change, and therefore, approaches commercialization on a drug-to-drug basis, Allan says. Typically, the company looks to have out-partnering deals by the Phase II stage of clinical development.

“The reason that tesmilifene and TheraCIM are still, by great good fortune, in our portfolio and not partnered, is just dumb luck,” he says.

Allan explains that tesmilifene had originally been licensed from the University of Manitoba (Winnipeg, MB) to Bristol Myers Squibb Co. (New York, NY), which had conducted the first Phase III trial. For that trial, Bristol had set tumour response rate as an end point, rather than survival.

At the time the trial was being conducted, tumour response rate was seen to correlate with survival. However, when Bristol was not seeing any difference in tumour response between the two arms of the trial, it returned the licence to the university, at which time YM took on the drug and the U.S. National Cancer Institute completed the trial that demonstrated the impressive survival statistics.

Though this turn of events ended up benefiting YM, the company is not considering changing its overall approach to commercialization, Allan says.

“This should not become the new creed in house — let’s keep everything. Because the fact of the matter is, we’re really not in that business,” he says. “We’re in the business of identifying earlier on drugs that we think will make an important difference to human health, to human life, and then take them to the point that we should sensibly be able to partner them out.”

Keeping Options Open

While YM now has a late-stage pipeline with its two lead products, despite its desires to partner, holding onto a drug further into the process isn’t so random for all companies. Two other firms that have cancer drugs in late-stage clinical trials purposefully seek out this route to market.

For Lorus Therapeutics Inc. (Toronto, ON), multiple plans of action are in place when it comes to drug commercialization.

The company’s lead product, Virulizin®, works by enhancing immune system cells called macrophages. By increasing macrophages’ cytotoxic effect, Virulizin enhances these cells’ ability to kill cancer cells.

Approved for malignant melanoma, and currently in Phase III trials for pancreatic cancer, Virulizin has already proven to be a successful product for Lorus.

“Our general policy has always been to develop the drugs as far as possible prior to partnering, because as you begin to bring the drugs forward into later-stage development, you reduce the risks involved and the better the deal that you can expect at the end of the day,” says Lorus president and CEO Jim Wright, PhD.

The company is currently considering both partnership opportunities and moving Virulizin forward itself, depending on which option works best for the company and the drug, Wright says.

“Our commercialization plans will differ for every product because, essentially, timing is a factor, finance is another factor,” says Germaine Gross, director of Business Development.

Along with developing its own in-house research, Lorus also takes other approaches to achieving commercialization success. In 1999, Lorus acquired GeneSense Technologies Inc., a deal that provided Lorus with GTI2040, a product that has multiple cancer indications, and GTI2501 for prostate cancer. Both drugs are currently in Phase II trials.

“One of the things about our company is we do have a very broad pipeline of different anticancer drugs. We did that on purpose because that mitigates the risk again for our investors, because if one particular approach isn’t successful, the company doesn’t live and die on that, because it has many other approaches and potential products as well,” Wright says.

Navigating Speed Bumps

That line of thought has come in particularly handy for Biomira Inc. (Edmonton, AB), which has been faced with just such a situation.

One of the company’s two lead products, Theratope®, did not meet the end points of a Phase III trial. Following the results, Merck KgaA (Darmstadt, Germany), which was collaborating with Biomira on Theratope, pulled out of further work involving that drug.

Theratope is a disaccharide that, when injected along with a non-specific immune stimulant, causes antibody production against a marker found on breast cancer cells.

Though Theratope did not meet the set end points, it did demonstrate some positive results in a subset of patients. To better understand these findings, Biomira is currently conducting mechanism of action studies, and at the same time is looking for new out-licensing partners for Theratope, says Biomira president and CEO Dr. Alex McPherson, PhD.

Despite this challenge, Biomira is still in the game, thanks in part to having more than one drug in late-stage trials at one time. Biomira is still collaborating with Merck on its other lead product, BLP25 liposomal vaccine (L-BLP25), which the two companies are investigating for lung cancer and other indications.

“The collaboration is going very well with Merck,” says Bob Aubrey, vice-president of Business Development. “I can understand why they chose BLP25, when you’ve got two drugs that could be launched in about the same time frame.”

Encapsulated in a liposome, L-BLP25 is a 25 amino acid peptide that stimulates T-cell response, which received fast track status from the U.S. Food and Drug Administration last fall. L-BLP25 is expected to enter a Phase III trial late this year or early next year, following a bridging, or clinical experience study to compare the product Biomira is proposing for the Phase III trial and product launch with the product used in the Phase II trial, McPherson explains.

Though Biomira also keeps its products into later stages of clinical development before partnering, commercialization is something the company starts thinking about right as the drugs enter the clinic.

“From Phase I onward, you have to incorporate business development and marketing, sales and distribution people in the conversation very early on in the game,” McPherson says. “In this business, for instance, it’s probably not a particularly wise thing to look at expending in excess of $250 million US on a product that has a market of $1.5 million.”

Along with these strategies, Biomira spun off Oncodigm BioPharma Inc. in 2004 in order to better maximize the commercialization potential of a drug that was getting pushed to the side thanks to Theratope and L-BLP25’s prominence.

“We’re quite fortunate, and our shareholders have been fortunate that we had BLP25 right behind Theratope. And that’s a good thing, and that’s got a downside in that we had a drug called liposomal IL2,” Aubrey explains, who is also on Oncodigm’s board of directors. “So we had the concept of putting that into a different company who had a liposomal drug charter, so to speak.”

Biomira clearly benefits from having established Oncodigm as a separate company focused on moving another product forward. The company has right of first negotiation for the lead drug, liposomal IL2, after Phase II to become the North American marketing partner, and is also a major shareholder in the spinoff.

For any company on the road to commercialization, it seems that giving yourself various routes to travel is the best course of action.

“There is no one way to do anything, and that’s really the bottom line,” Wright says. “And if you have multiple products in different stages of development, different mechanisms of action, then you’re probably going to have different ways of developing it and bringing it forward and commercializing it.”