Denali grabs $130M more as it heads into the clinic, reveals deals

a black and white drawing of a human brain

Denali Therapeutics has huge ambitions--to treat some of the most intractable and complex ailments, neurodegenerative diseases. Despite the potential cautions presented by such difficult terrain, investors have plowed another $130 million into a Series B to back the startup that’s led by Genentech vets. The latest infusion brings its total raised to almost $350 million.

The company has filed to start its first Phase I trial in Europe for a small molecule RIP1 inhibitor that can penetrate into the central nervous system (CNS). RIP1 is a kinase involved in regulating inflammatory signaling that can affect the brain’s glial dysfunction. The drug is slated to be tested in ALS (Amyotrophic Lateral Sclerosis) and Alzheimer's disease patients, after this initial safety trial in healthy volunteers.

"Mounting genetic evidence points to glial dysfunction as an accelerator of neurodegeneration, and we believe that advancing our RIP1 inhibitor into human clinical testing is a significant step in bringing forward a novel mechanism to combat ALS and Alzheimer's disease," said Denali CMO Dr. Carole Ho in a statement. She was previously the VP of Early Clinical Development at Genentech.

Denali is focused on four specific pathways that it sees as triggers or effectors of neurodegeneration: degenogenes (genes that cause neurodegenerative disease when mutated), defective intracellular trafficking, glial dysfunction and axon degeneration. It aims to develop treatment strategies for each of these that are driven by biomarkers.

The South San Francisco, CA-based company ultimately aims to have a portfolio of therapies to address diseases including Alzheimer's disease, Parkinson's disease, ALS and others. The financing and deals are aimed at “building out Denali's systematic and novel approaches and capabilities to defeat degeneration," described Denali CEO Ryan Watts. He was the Director of the Department of Neuroscience at Genentech.

Denali disclosed a handful of deals that give it access to a range of new technology and approaches to neurodegenerative diseases headed up by the acquisition of Incro Pharmaceuticals for its RIP1 inhibitor program that’s in-licensed from Harvard University and a global license with Roche’s Genentech ($ROG) to develop and commercialize LRRK2 inhibitors for the treatment of Parkinson's disease.

"Partnerships are central to Denali's strategy and we continue to seek collaborations to discover and develop effective medicines for patients," said Denali COO Dr. Alex Schuth in a statement. He was the Director and Head Technology and Diagnostics Partnering and, prior to that, the Head of Neuroscience Partnering at Genentech.

In addition, Denali disclosed a trio of research collaborations with: Washington University School of Medicine to develop and market antibodies targeting ApoE in Alzheimer’s disease; the U.K.’s F-Star to develop therapies that cross the blood-brain barrier; and Blaze Bioscience to research and discover drugs that cross the blood-brain barrier at the Fred Hutchinson Cancer Research Center.

The latest financing was led by U.K.-based mutual fund Baillie Gifford with participation from several, undisclosed, “new and large institutional investors,” the company said. All the founding investors participated; its Series A investors include Alaska Permanent Fund, ARCH Venture Partners, Flagship Ventures and F-Prime Capital Partners.

- here is the release

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