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Neuroscience

Biogen buys into Denali’s Parkinson’s disease drug candidates

The deal helps diversify the big biotech’s pipeline beyond Alzheimer’s disease

by Lisa M. Jarvis
August 12, 2020 | A version of this story appeared in Volume 98, Issue 31

 

A photo of PET brain scans.
Credit: Biogen
In a preliminary study, Biogen’s aducanumab reduced the amount of amyloid (in red) in the brains of people with early-stage Alzheimer’s. Left, pretreatment; right, after 54 weeks of the drug

Biogen is committing over $1 billion—$560 million in cash and $465 million in equity—to Denali Therapeutics as part of a Parkinson’s disease partnership. The deal, meant to ease Biogen’s reliance on drugs for Alzheimer’s disease, gives the firm access to a clinical-stage Parkinson’s drug as well as the right to buy into other neurodegenerative disease programs.

The investment expands Biogen’s Parkinson’s disease portfolio, which includes an alpha-synuclein-targeted antibody, to encompass Denali’s small-molecule inhibitors of LRRK2, an enzyme encoded by a gene frequently mutated in people with the disease. The companies will jointly develop Denali’s lead molecule, DNL151, which is expected to begin late-stage trials next year, in the US and China.

As part of the deal, Biogen also gains the right to buy into two neurodegenerative disease candidates that use Denali’s drug-delivery technology, which shuttles molecules across the blood-brain barrier. While it keeps pathogens out of one of our most precious organs, the blood-brain barrier also often keeps out drugs meant to address neurodegenerative diseases.

Denali’s technology tries to overcome that problem by tethering a drug to a protein engineered to bind to the transferrin receptor, which normally pulls iron into the brain. The biotech firm recently showed that its vehicle was effective at sneaking an antibody targeting an enzyme associated with Alzheimer’s disease into the brains of mice and monkeys.

Stock analysts say the partnership is sound but that it comes at a steep price. It also isn’t enough to distract from Biogen’s upcoming make-or-break moment for aducanumab, its Alzheimer’s disease treatment. The company recently said the US Food and Drug Administration has agreed to review its application for aducanumab. The agency has a deadline of March 7, 2021, to decide whether or not to approve the anti-amyloid antibody.

Aducanumab made headlines for appearing to clear amyloid plaques and slow cognitive decline in preliminary studies, but it did not show benefits in larger trials. Biogen is asking for FDA approval of the drug based on a new analysis of the data suggesting a high dose of the drug is effective.

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