Denali

Dr. Ryan Watts, third from left, with team members Steve Krognes, Carole Ho, Alexander Schuth.

Summiting the tallest mountain in North America is a significant undertaking and a life-changingaccomplishment. Denali is not only the tallest mountain onthe continent but the tallestmountain in the world measured from above ground base to peak. As such, the challenge and potential of mountaineering are reflected in both the name and purpose of Denali Therapeutics, a biotechnology company focused on finding treatments and cures for degenerative illnesses, such as Alzheimer’s and arkinson’s disease.

This association with mountains is less surprising when you meet the CEO and Co-Founder of Denali Therapeutics, Dr. Ryan Watts. A College of Science alumnus in Biology, Watts gained an early appreciation for mountains growing up in Holladay, Utah, in the shadow of Mount Olympus.

Now, Watts and his colleagues are passionate about discovering drug therapies to help over 22 million people across the world who are fighting crippling neurodegenerative illnesses. As life expectancies rise across the

world due to improved nutrition and effective treatments for some diseases, Alzheimer’s disease and other age-related neurodegenerative diseases are reaching epidemic proportions. Expressed solely in financial terms, the cost of treating people with Alzheimer’s and other dementias is estimated to exceed $260 billion by 2020 in the U.S. alone.

A product and proponent of public education,Watts graduated from Cottonwood High School and came to the University of Utah,reflecting his desire to attend a top-tier research institution. As an undergraduate,Watts was still figuring out where he wanted to focus his talents. He started out as a Chemistry student, but saw the fields of Cell Biology and Human Genetics as the future. However, it wasn’t until he got the opportunity to conduct undergraduate research in the Department of Biology that Ryan discovered the

passion that would determinehis career path. Along withhis undergraduate researchexperience, Ryan also servedas a teaching assistant forDr. Baldomero “Toto” Oliveraand was a Pediatric Technician in Surgery atPrimary Children’s Medical Center.

Watts was particularly impacted by his interactions with Dr. Olivera because he recognized how Olivera’s biochemical insights could be translated into treatments for pain. Ryan excelled in the lab and the classroom, and upon graduation was accepted into Stanford University’s Biological Sciences doctoral program.Watts recalls that there were just a few fellow students from his graduate school class who had completed their undergraduate degrees at public institutions, but that his experiences at the U had prepared him well.

At Stanford, Ryan continued to distinguish himself in research and received his Ph.D. in 2004, focusing on the molecules that regulate nervous system development. Afterwards, he accepted a position at Genentech, a company known for breaking new ground in cloning.

genes. During his eleven-year tenure there, Watts and his colleagues focused initially on developing therapies for cancer, then switched their attention to neurodegenerative diseases. He led Genentech’s entry into Alzheimer’s disease discovery and drug development, eventually building and leading their newly created Neuroscience Labs.

Watts and a select group of neuroscientists and investors eventually formed a biotech startup named Denali Therapeutics. In contrast to the broad approach of companies like Genentech, Denali would be fully specialized in solving the mystery of neurodegeneration.

Founded in 2015, and headquartered in South San Francisco, Denali Therapeutics has already raised more than $349 million and grown to more than 110 employees. Watts and his colleagues have the talent, passion and focus needed to take on these devastating illnesses, but recognize that it will be incredibly difficult as they are blazing new trails.

As the name Denali suggests, the treatment and study of neurodegenerative diseases pose significant challenges. These conditions, and therefore the therapies targeting them,

In contrast to cancer, neurodegeneration is both more difficult to target than cancerous tumors and has fewer and less well-defined biomarkers. Interventions also tend to be slower-acting, and it takes longer to see whether a treatment had positive, negative, or no effect.

Watts cites four major barriers to developing medicines to stop neurodegeneration:

• A lack of drug targets

• Passing the blood-brain barrier to get drugs into the brain

• Difficulty in identifying biomarkers to track drug activity

• Identifying the right dose for the right patient at the right time.

Watts recalls a quote from Louis Pasteur that he first heard while sitting at a microscope in the Skaggs Biology Building at the U: “chance favors only the prepared mind.” Watts applies this principle at Denali Therapeutics, where the team has been assembled with experienced drug developers combined with some of the best researchers in the field of neuroscience. Like a team of mountain climbers preparing to ascend a peak, the researchers at DenaliTherapeutics are equipped with deep knowledge,interdisciplinary specializations, and adiverse set of approaches to problem solving,ready to pursue their goal of finding a cure forneurodegenerative illnesses and advancingscientific research.

Reflecting on his time as a student atthe U, Watts has some advice for the currentgeneration of students.“Build connections with thegreat faculty at the U andexplore opportunities to getin the research lab as soon aspossible. Top notch researchuniversities like the U offer aunique chance to discoveroriginal insights as part of your education.”

Watts is driven both by a love for research and the vision that Denali Therapeutics could better humankind. And it was as an undergraduate student at the U that Watts first discovered this drive and began acquiring the skills needed to make his vision a reality.

Editor’s note: The Watts family tradition at the University of Utah will continue this coming fall. Ryan’s oldest son, Tanner, will be enrolled as a freshman, planning to study bioengineering.