The Alzheimer’s R&D Race : AbbVie, Alector, Aducanumab
For well over a decade now, the major focus in Alzheimer’s R&D has been concentrating heavily — though not exclusively — on the tangles of toxic amyloid beta and tau that are often associated with the disease. Alector set out to do things differently, though, with a focus on the innate immune response in the brain. Now as investigators for the little biotech aim for the clinic, AbbVie wants in, paying a whopping $205 million in cash — with $20 million reserved for an upcoming round — and promising an undisclosed multiple in milestones to partner on the work.
AbbVie already has an in-house program on tau. But looking a few years ahead to when the Humira franchise faces generic competition, they’re doubling down on Alzheimer’s and a range of diseases that fall under the heading of neurodegeneration. A win here would be huge, and AbbVie is willing to bet big. The way Alector thinks of things, neurodegeneration and dementia are caused by inactivity of the immune system. And taking a cue from immuno-oncology — where they have a secondary, parallel program in place — Alector has been developing a preclinical pipeline of antibodies that are designed to act to either accelerate the immune system or selectively remove the brakes that are in place. If they’re right, the microglia in the brain can go a long way to gobbling up the toxic proteins that may be the central players in driving Alzheimer’s.
“We will go into the clinic a year from now, and we’re planning to bring 5 drugs into the clinic in the next 18 months,” says Robert Paul, the chief medical officer at Alector. Those drugs are coming directly from Adimab, Tillman Gerngross’s shop near Dartmouth in New Hampshire. Gerngross is the chairman and co-founder at South San Francisco-based Alector, which is run by Genentech veteran Arnon Rosenthal. And he’s had decades to perfect new antibodies for the clients he works with, selling turnkey antibody development platforms to the major developers in the industry or devising pipelines for the biotechs he helps found. In this new deal, AbbVie vaults from a venture backer — helping to arrange the first $80 million in funding — to a close collaborator.
AbbVie will get an option on two of Alector’s therapies, which the biotech will take through proof-of-concept studies. If AbbVie picks up its options, they will then co-fund development in a drive to commercialize the therapies — with a profit split for anything that gets approved. In addition to the $205 million in cash, AbbVie is setting aside $20 million for an added equity stake in Alector, which is concurrently raising a big new round, with a syndicate that includes Merck, OrbiMed, Polaris, Mission Bay Capital and Topspin Partners. The milestones are undisclosed, but in a preclinical deal that starts out with $225 million up front, they almost certainly run into 10 figures.
They’ll need the money.
Neurodegeneration development does not come cheap, and Alector wants to move a pipeline into the clinic, rather than just one or two candidates. Alector and AbbVie also are acutely aware of the potential here. “If these drugs are successful, they are going to become blockbuster biologics,” says Sabah Oney, the head of business development at the biotech.
For the past 15 years, that blockbuster beacon has driven a growing slate of bitter Phase III failures. The latest was at Axovant, a brash upstart that thought it could do what GlaxoSmithKline and rivals had tried by amping up neurotransmitters. Eli Lilly had three straight defeats with solanezumab, and still hasn’t given up on it. And now BACE and other strategies are being put to the test, with early failures pointing to the potential for more disaster as well. Still, Biogen’s mixed success with aducanumab has emboldened many of the big players, like Roche, to go back to the drawing board.
Alector and AbbVie want to try something different now, and it will take years to see if it works.