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A Neuroscience Fireside Chat with Ryan Watts at 2016 BIO Investor Forum

October 19, 2016
The 2106 BIO Investor Forum held a Fireside Chat with Ryan Watts, PhD on Tuesday, October 18 moderated by:

  • Andrew Fein, Managing Director and Senior Healthcare Analyst, Research Division at H.C. Wainwright & Co., LLC.

  • Rachel Lane, PhD, Equity Research, Biotechnology at H.C. Wainwright & Co., LLC


Ryan Watts, PhD, is the current Chief Executive Officer at Denali Therapeutics Inc. in addition to being a co-founder and a member of the Board of Directors. Previously, he served as Director of the Department of Neuroscience at Genentech, where he was employed for 11 years. During his tenure there, he led the company’s entry into neuroscience, building a department and advancing multiple programs for neurological disease from discovery to clinical testing. Ryan’s own laboratory focused on drug discovery for Alzheimer’s disease and on understanding mechanisms of neurodegeneration guided by human genetics. Ryan is also a leader in the development of improved methods for delivering therapeutic antibodies across the blood-brain barrier.

With such an impressive background we couldn’t wait to sit down and hear more…

It was one of the first things mentioned - the neurodegenerative space is notoriously known for being one of the highest failing areas. So what do you do when you find yourself in that 99% fail group? Ryan believes it’s imperative to learn from those failures. While data isn’t always available in this space, when it is, questions like “why this target” or “was there engagement” need to be asked. It’s an obvious challenge when the basic principles of drug development don’t apply to the brain. While there are still major advances that need to be made, in the last five years, Ryan shares that discoveries and understanding of the neurodegenerative space have really accelerated. In addition to genetic discoveries, drugs reaching targets and engaging have been initially observed. As we wait for dedicated innovators to find a cure, the best that can be currently done is catching the disease as early as possible and seeking out treatment before onset.

The questions that then begs to be asked is how does Ryan envision success happening?

At Denali, there are two driving principles: pathway potential defined by human genetics and drugs reaching the brain. With the blood-brain barrier being so unique, it requires building equally unique expertise. While at Genentech, Ryan saw high success in partnerships and now equally values partnerships at Denali. Knowing that partnerships can accelerate efforts, Ryan discussed how they selected various areas of expertise and now have 15 partnerships – some for drugs, some in engineering and discovery to eventually cross that blood-brain barrier, and a number with clinical end points. This model allows them a shot in the toughest therapeutic area. It’s partnerships like these with both industry and government that grants access to longitudinal data providing an understanding of progression in neurodegenerative disease. These collaborations are producing the exciting data which provide insights to potential therapies.

When questioned about drug development, Ryan confirms that it’s an ideal time for these efforts given that most genetic discoveries in the last five to 10 years have happened in this space. Committed to finding a cure, Ryan says he’d happily cheer on the success of his colleagues. He compares this time to the initial successes in oncology – it created a wave of discovery and invention. With a 99% fail rate in the field, it’s difficult to fund an area with probably the most need. Their success will have a major, positive impact, in turn paving the road to success for everyone else in this field.

Ryan concluded his Fireside Chat with key takeaways about how to best position your company for success: have an underlying desire to solve and make advances in the disease, have long term commitment, break down huge problems into areas you can tackle, but most importantly engaging in those key partnerships.