What You Need to Know About Denali

January 9, 2017
By Mark Terry, BioSpace.com Breaking News Staff

Denali Therapeutics was launched in May 2015 by three former Genentech researchers—Ryan Watts, former director of Genentech ’s Department of Neuroscience, Alexander Schuth, former director and head of Genentech’s Neuroscience Partnering, and Marc Tessier-Lavigne, president of The Rockefeller University.

The company’s focus is on translational research for the development of drugs to treat neurodegenerative diseases such as Alzheimer’s, Parkinson’s, ALS and others.

“Our team will place an emphasis on rigorous translational medicine for targeted drug development,” Watts, the Denali’s co-founder, president and chief executive officer said in a statement at the time, “seeking evidence of drug activity in the brain and identifying biomarker-defined patient populations to increase the probability of clinical success. We are committed to collaborating with leading academic groups, companies and advocacy groups.”

Denali is researching newly discovered genes tied to degenerative brain diseases, which the company founders are calling degenogenes. Their focus is on the nascent field of how inflammation affects neural diseases.

Company Leadership
Ryan Watts—co-founder, president and chief executive officer. Watts previously was director of the Department of Neuroscience at Genentech.

Alexander Schuth—co-founder and chief operating officer. Before joining Denali, Schuth was head of Neuroscience Partnering at Genentech.

Carole Ho—chief medical officer. Prior to Denali, Ho was vice president of Genentech Early Clinical Development.

Steve Krognes—chief financial officer. Before Denali, Krognes was chief financial officer and a member of the Executive Committee at Genentech. Before that he led the global Mergers & Acquisition team at Roche in Switzerland.

Mark Dresser—head of development sciences. Prior to joining Denali, Dresser was the director and head of the Oncology Clinical Pharmacology Department and the Atezolizumab (anti-PDL1) Project Team Leader at Genentech.

Cindy Dunkle—head of human resources. Before joining Denali, Dunkle had roles of increasing responsibility across corporate staffing and development functions at Avalanche Biotechnologies and Genentech.

Joe Lewcock—head of biology discovery. Prior to Denali, Lewcock was director of the Department of Neuroscience at Genentech.

Zach Sweeney—head of therapeutic discovery. Previously, Sweeney was a director of Global Discovery Chemistry and head of Analytical Chemistry at Novartis Emeryville.

Company Financing
Denali launched with $217 million in venture capital. Additional investors include Fidelity Biosciences, ARCH Venture Partners, Flagship Ventures, and the Alaska Permanent Fund, represented by Crestline. Other investors include sovereign wealth funds, public mutual funds and private family offices.

On August 25, 2016, the company announced a $130 million Series B equity financing. All of its founding investors participated in this round, which was led by Baillie Gifford, a UK-based mutual fund and included several new and large institutional investors, who were not identified.

Pipeline
Denali also announced in August its first Clinical Trial Application (CTA) to initiate a Phase I trial. It has selected four specific pathways that are believed to be triggers or effectors of neurodegeneration. Those include degenogenes, defective intracellular trafficking, glial dysfunction, and axon degeneration.

The CTA in Europe is for a small molecule RIP1 inhibitor with central nervous system (CNS) penetrant properties. RIP1 is a kinase that regulates inflammatory signaling and affects glial dysfunction in the brain. Data from the study would then be used to design studies for ALS and Alzheimer’s disease.

“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 Ho in a statement last August.

Market Competition
The field of neurodegenerative research is a crowded one, with Biogen , Eli Lilly , Merck and Genentech (ROG) all working on Alzheimer’s and other CNS disorders.

Dollars and Deals
In August 2015, the company announced a number of deals and transactions. It acquired San Diego-based Incro Pharmaceuticals for access to its RIP1 inhibitor program, which came out of a license and collaboration deal with Harvard University. Denali also inked a license agreement with Genentech for exclusive global rights to develop and commercialize LRRK2 inhibitors for Parkinson’s disease. Denali signed a research collaboration and exclusive license agreement with Washington University School of Medicine in St. Louis to develop and commercialize antibodies targeting ApoE, a protein and genetic risk factor for Alzheimer’s disease.

In addition, Denali has a research and option deal with UK-based F-star in support of the development of a platform technology that can deliver therapeutics across the blood-brain barrier. And Denali inked a collaboration and option deal with Blaze Bioscience for a novel blood-brain-barrier drug at the Fred Hutchinson Cancer Research Center.

Other strategic partnerships include collaborations with ALS Therapy Development Institute, Aptuit, Evotec, Massachusetts General Hospital, The Michael J. Fox Foundation, PatientsLikeMe and the University of California San Diego School of Medicine.

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