Drug Development

Denali launches a clinical quest on Alzheimer’s drug, banking $155M in Takeda cash and scoring monkey data on BACE

After all the setbacks and failures we’ve seen in Alzheimer’s research over the past 15 years, can a startup boasting better technology beat the terrible odds against them and score with a new drug?

We’re at the early stages of getting an answer to that question.

Denali $DNLI announced today that it is now trying just that, launching a Phase I clinical study of its Alzheimer’s drug DNL747, its small molecule inhibitor for RIPK1. It’s also started a second human study of its LRRK2 inhibitor for Parkinson’s disease, which is its lead indication. And the South San Francisco biotech reported that it’s banked a $155 million upfront from Takeda’s billion-dollar partnership while scoring positive early results from a study involving monkeys for BACE1 — a mechanism in Alzheimer’s that recently failed decisively for Merck in Phase III.

That primate study is particularly important, as it helps validate Denali’s belief that its Antibody Transport Vehicle — or ATV — technology can get past the blood brain barrier and deliver a therapy into the brain — a hurdle that has stymied developers in the past.

Alzheimer’s has proven to be the hardest target in biopharma R&D, defeating everything thrown at it for well over a decade in pivotal trials. Merck’s recent failure on BACE, eliminating production of amyloid beta in patients, proved to their researchers that it wouldn’t work in mid-to-moderate patients. And they’re in the process of evaluating the numbers for prodomal patients, where verubecestat also failed.

Despite the litany of failures, though, the ex-Genentech gang — led by CEO Ryan Watts — that runs Denali have pieced together one of the most closely-watched efforts in the field, starting over with genetically defined patient groups and using new tech from companies like F-star. And despite the skepticism over targets and disease modification, the biotech has been able to store $467 million in cash by the end of December, building a market cap close to $2 billion — before the Takeda payment came through. And the global pharma company is on the hook for another $85 million in preclinical milestones.


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Associate Principal, Life Sciences Partnerships
Flatiron Health New York City or San Francisco
Head of Business Development
Wren Therapeutics Boston, MA
Life Sciences Venture Professional
Northpond Ventures Washington, DC

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