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Alder Steers Next Antibodies To Unusual Places: Treating Migraines and High Cholesterol

Xconomy Seattle — 

Alder Biopharmaceuticals prides itself on challenging conventional wisdom. But while Alder has proved the skeptics wrong, showing it can make targeted antibody therapies in a new way with cheap and fast-dividing yeast cells, it has used this technology in a pretty conventional way—to make weapons against cancer and autoimmunity.

Now Alder is stepping out with two really unusual ideas on how to use antibodies in ways they’ve never been used before.

The Bothell, WA-based biotech company, which enticed Bristol-Myers Squibb to enter into a $1 billion partnership in 2009 to co-develop its lead drug for rheumatoid arthritis, is unveiling a couple interesting new antibodies from its discovery pipeline. These new drug candidates, which Alder is discussing today at Life Science Innovation Northwest in Seattle, are aimed at two diseases that have never been treated with antibodies—migraine headaches and high cholesterol.

The idea is to find another way to exploit Alder’s underlying technology in a place where fewer competitors tread, yet where there is still money to be made. Alder’s yeast-based system is made to be cheaper and faster at churning out antibody drugs than the usual bacterial or mammalian cells used by other companies. Partly because of the high costs of making antibodies today, most companies have developed them against diseases like cancer—where drugs can command prices of as high as $100,000. Alder’s idea is to use its more flexible platform to break out of that groove, and think about using antibodies against other chronic diseases that require lower-cost therapies.

There are still plenty of risks here, not the least of which includes whether people will pay something in the ballpark of $5,000 to $8,000 a year for a migraine treatment. Alder’s drugs are also a long way from hitting the radar of your average physician: Alder’s new migraine drug candidate is being prepped for its first clinical trial later this year, and the cardiovascular drug could enter its first human test in late 2011, or early 2012, CEO Randy Schatzman says.

Randy Schatzman

“When people typically think of antibodies in autoimmune disease and cancer, the rationale often is that these are indications in which people will tolerate the high price of those medicines, and these are indications in which people will tolerate some of the safety issues,” Schatzman says. “But we’ve been thinking, are there non-traditional markets where antibodies can play a role that people haven’t thought about in the past, but where we understand the biology?”

Migraine headaches affect an estimated 30 million people in the U.S., and nobody has ever come up with a drug that stops migraine pain before it starts. There is a family of “triptan” based drugs which generated about $3 billion in worldwide sales in 2008, although the former market leader—GlaxoSmithKline’s sumatriptan (Imitrex)—recently lost its patent and began to face generic competition.

Drugs in this class, which work by constricting blood flow to the brain, aren’t really a cure-all. They have to be taken once a patient already feels migraine pain, and then they offer some relief for half to three-fourths of patients within two hours. They don’t last a full 24 hours, allowing room for so-called “rebound” headaches. The drugs also come with a warning that they can cause high blood pressure and other side effects like stroke. The field has seen very little innovation in recent years, although one of the new entrants is botulinum toxin (Botox, yeah, that Botox) from Allergan.

Alder is seeking to tackle this problem differently. It has been able to make antibodies that last months in the bloodstream, raising the possibility that it could make an drug that’s injected just once a month or even once a quarter. It has made an antibody designed to zero in on a protein target called CGRP, involved in blood vessel constriction. The hope is that for severe migraine sufferers—folks who say they get as many as 20 headaches a month—this drug could stick around in the bloodstream, essentially preventing most of those episodes from happening through a once-monthly injection.

“If you’re someone who gets 20 [headaches] a month, and take a shot at the beginning of the month and reduce headache frequency by 50 percent, that would be a grand slam home run,” says Alder’s chief scientist John Latham.

Alder’s other antibody is going down a more beaten track—cholesterol lowering. Schatzman knew what I was going to ask before it even popped out of my mouth. Why would anybody want to develop another cholesterol-lowering drug, when statins have been so successful, taken by millions of people, and many have gone generic or will soon go that cheap commodity route?

Turns out that Alder is approaching this market by focusing not on the millions of people who take statins, but on the rare populations of patients with genetic disorders that cause them to have uncontrolled high cholesterol, and as an option for those who don’t tolerate statins well. This is familiar territory to followers of Cambridge, MA-based Genzyme (NASDAQ: GENZ) and Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS), who are in late stages of development with a drug called mipomersen, which is a targeted medicine like an antibody, but which uses a different form of biotechnology called antisense.

Alder is aiming its antibody at a target called PCSK9, which cardiovascular researchers have tried, with no luck, to make conventional small molecule drugs against. Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY), a leader in RNA interference, has said it is working to specifically shut down the activity of this biological target, as a new way of lowering cholesterol.

Alder is aware it’s not alone here, but Schatzman, as you’d expect an antibody guy to say, says he prefers to take an antibody drug into this field. One reason: dose convenience. If Alder can make an antibody last in the bloodstream for a month or more, then it could be injected infrequently. By keeping an active drug in the bloodstream for a longer period of time, cholesterol should remain more steady than the way it currently does with many people, whose blood levels fluctuate when they forget to take their daily pills.

Alder, like it did in the early days with its lead molecule ALD518, spent a lot of time sussing out what key medical researchers thought about its ideas of using antibodies in these patient groups. It sounds like the management team got some funny looks in the early going, but support is building, Schatzman says.

“We’ve heard people say, ‘This is really out of the box thinking,'” Schatzman says. At least for the migraine program, “this will be a very interesting molecule if the clinical results look like we think they will,” he says.

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