When you say the words multiple sclerosis treatment or cancer immunotherapy, Alkermes (NASDAQ: ALKS) isn’t the first company that comes to mind. But the Dublin and Waltham, MA-based biotech is trying to change that today as it rolls out a few key programs it has been keeping under wraps.
At its R&D day today, Alkermes is unveiling three new programs coming that have been in stealth mode up until now: a program of small-molecule monomethyl fumarate drugs to treat multiple sclerosis; a cancer immunotherapy candidate known as RDB-1419; and a non-addictive pain relief pill called ALKS-7106. The announcements continue Alkermes’ metamorphosis into a fully integrated company with enough cash flow from marketed products to support a good-sized R&D portfolio. The changes at Alkermes have helped vault its market capitalization up to more than $4 billion over the past few years.
“It’s a really important transformational moment for the company,” says CEO Richard Pops.
Even so, it’s one that is also likely to give investors pause: what makes Alkermes think it its own drugs can compete in ultra-competitive fields like MS and cancer immunotherapy? MS powerhouse Biogen Idec (NASDAQ: BIIB) began selling dimethyl fumarate (Tecfidera)—a long-awaited oral pill for MS—this year and it has, by all accounts, been every bit the success it was hyped to be. And cancer immunotherapies, which harness the immune system to fight cancer, are part of a turf war being fought by the likes of Bristol-Myers Squibb, Roche, and Merck.
But Pops isn’t shying away from the challenge. Alkermes wants to take on chronic diseases that affect lots of patients, and it sees a way to put itself into the mix. This isn’t to say Alkermes wants to dive full-bore into cancer or MS, or pour millions into finding undiscovered molecular targets the rest of the industry hasn’t found. Rather, it wants to pick its spots in a big disease area, find a place it can add tangible value, and strike.
Here’s how: Alkermes thinks it can take either known pharmacology, or well-studied or proven molecular targets, and add value to them by creating new molecular entities that have a big benefit for specific patient groups. This is the strategy that made Alkermes successful for years, by helping develop longer-lasting versions of drugs like risperidone (Risperdal Consta) for schizophrenia and exenatide (Bydureon) for Type 2 diabetes. The company’s R&D team is looking to build on successes like that, by engineering improvements into both branded drugs like Biogen’s new oral MS pill, and generic products like olanzapine, a compound that once made big money for Eli Lilly under the brand name Zyprexa.
“We’re not daunted at all by the fact that certain therapeutic categories have multiple entrants,” Pops says. “We wouldn’t go there if we didn’t think that we could make a major contribution in a very, very clear and directed way.”
Take MS, for example. Pops notes that Biogen’s drug is actually an “old molecule” that is “imperfect” in its current form that has certain tolerability issues. Alkermes says it can make the drug better by using its R&D engine to create a prodrug—an inactive substance that enzymes or other chemicals in the body turn into a drug— that yields a product that is better than dimethyl fumarate by either being more tolerable, or lasting longer in the body. This, for instance, could lead Alkermes to make a once-daily dose of the MS drug, as opposed to the twice-daily dosing required by the existing drug.
Pops also says that by improving upon Biogen’s drug, Alkermes is significantly lowering the risk that its drug candidates will fail in clinical trials. This is because Alkermes will essentially pre-suppose the drug works while using the first, small clinical trial to find out things like how effectively and quickly the drug is being delivered into the body, and how people are tolerating it.
“The idea is to participate in this gigantic market with a value-added and differentiated product where the technical risk after the early clinical trials is significantly attenuated,” Pops says. “We’re trying to view it from the perspective of a patient taking that medicine with a chronic disease for a long period of time where flushing, [gastrointestinal] irritation, and twice a day dosing can become issues over time.”
Alkermes is working on two specific prodrugs to start, though it is also putting together other formulations behind it, according to Pops. It hopes to kick off an early-stage trial based on that work in the middle of 2014.
Then there’s Alkermes’ first shot at cancer immunotherapy. Alkermes’ idea is to use certain protein engineering techniques to change existing molecules to improve their safety, efficacy, or pharmacologic characteristics. In this case, Alkermes believes it can use those techniques to soup up an immune-boosting molecule known as interleukin 2, or IL-2, which is sometimes used for treating melanoma, a deadly skin cancer. Pops says IL-2’s practical use has been limited due to toxicity problems—it binds to things that both help, and ultimately harm, the body. Alkermes plans to get around that by creating a “fused protein” that behaves differently in the body, Pops says.
“It binds to receptors that we want it to bind to with very high affinity, and the receptors we don’t want it to bind to—the ones that cause some of the underlying toxicity of IL-2—it doesn’t [bind] to as well,” he says.
Alkermes is currently conducting the work that will enable it to file an application to begin clinical trials.
The third drug, ALKS-7106, builds on Alkermes’ efforts over the past few years to create opioid-based pain relievers that have their addictive properties stunted on a molecular level. Another drug in Alkermes’ pipeline, a therapy for major depressive disorder known as ALKS-5461, does so by combining an opioid stimulator with an opioid inhibitor. ALKS-7106 works in a similar way. The benefit here is that patients shouldn’t be able to abuse, or overdose on the drug in the ways that they can with drugs like acetaminophen-hydrocodone (Vicodin). Alkermes plans to put that molecule in the clinic next year as well.
Of course, while Alkermes views each of these as huge opportunities, at this point, they haven’t produced a shred of evidence in human trials. But with its candidate for major depression having passed a mid-stage trial, two other experimental drugs for schizophrenia in clinical trials, and today’s additions in the early-stage part of the pipeline, Alkermes is trying to make the case that its evolving R&D portfolio will give it the chance to one day stack up with some of the bigger names in the industry.
“Our aspirational peers are Biogen, Gilead, Vertex, Regeneron,” Pops says. “We’ve told people very explicitly that our goal is to build one of the next major biotechnology companies. I think [today’s news] provides a little bit more ability for people to connect the dots and see why we’ve been so confident about that.”