Denali Therapeutics Inc.


Denali Therapeutics is dedicated to defeating neurodegenerative diseases by breaking through historical barriers in scientific research and clinical development in order to deliver safe and effective medicines to patients and families. Our scientific approach is based on three core principles: rigorous assessment of genetic targets, engineering brain delivery, and using biomarkers to guide development. Our team thrives in a work environment that is scientifically driven, impact-focused, supportive, and collaborative. Our ability to have a positive impact on people’s lives is directly related to the trust we have in each other and our ability to unify our diverse backgrounds and experience behind our purpose to defeat degeneration.

Treatment of neurological disorders has remained a crucial yet unmet need due to the difficulty of administering medicines in a way that is capable of reaching the brain. Our brains have approximately 400 miles of blood vessels that limit what can enter, known as the blood-brain barrier (BBB), which is designed to protect us from toxins entering our most complicated and perhaps important organ. In fact, the concentration of most therapeutic medicines in the brain is around only 0.1% of the concentration found in the blood.

Denali is leveraging genetics and pathology to develop a method of administering medicines that can effectively cross the blood-brain barrier by “hitching a ride” on transporters that allow necessary substances like glucose or iron to enter the brain.

The company utilizes a strict R&D process for all its programs. Denali initiates each program by identifying gene targets that are linked to a particular disease. Then, they engineer their molecules to cross the blood-brain barrier so that the therapy can effectively combat the neurological disorder. Finally, they use biomarkers to monitor the drug’s effects on patients and to effectively match patients with the right dosage during clinical development.

At the time of writing, Denali has made some progress on its pipeline with three therapies in the late-clinical development stage.

The Pipeline

Denali Therapeutics is potentially on the cusp of providing improved treatments for Parkinson’s, Hunter Syndrome, Alzheimer’s, ALS, and MS. Here are the drug candidates making that a possibility:

DNL151 (Parkinson’s)

Partnering with Biogen, the tandem targets the most common genetic risk factor for Parkinson’s, LRRK2. Increased levels of LRRK2 lead to the dysfunction of lysosomes, which contribute to the buildup of protein clumps in the brain that cause memory issues, behavioral changes, mood swings, and neurological degeneration. DNL151 is an inhibitor of LRRK2, and aims to ensure proper lysosome function.

DNL310 (Hunter Syndrome)

Hunter syndrome is an inherited genetic disorder caused by a missing or malfunctioning Iduronate 2-sulfatase (IDS) enzyme, causing abnormalities in the brain, skeleton, heart, and respiratory system. Denali’s drug candidate DNL310 is a recombinant IDS enzyme that is engineered to cross the blood-brain barrier and replace the patient’s existing IDS enzyme.

DNL788 (ALS, Alzheimer’s, MS)

In partnership with Sanofi, DNL788 is set to take on ALS, Alzheimer’s and MS by inhibiting RIPK1, which has shown beneficial effects in treating these diseases through preclinical trials. Increased levels of RIPK1 in the brain cause neuroinflammation and neurodegeneration, which lead to these diseases.

Operational Breakdown

Like many other early-stage biopharmaceutical companies, revenue generated by Denali does not come from actual product revenue as none of their product candidates have received regulatory approval and are commercialized for sale. All of Denali’s current revenue comes from collaboration agreements with Takeda, Biogen, and Sanofi. Denali funds its operations with stock offerings and payments made once reaching specified milestones through these collaboration agreements.


Denali Therapeutics has made great strides in tackling an unmet need and has backing from multiple major players in the pharmaceutical industry. Company CEO and co-founder Ryan Watts has personal motivations to drive the success of these drug candidates towards approval and commercialization as his mother suffers from Alzheimer’s. He also has a high risk of developing the disease, as he carries one of its most common genetic risk factors.

Denali’s technology to cross the blood-brain barrier could revolutionize the treatment of many diseases, including depression, psychosis, and even cancers that have metastasized to the brain.


Founded 2015
Type Public
Location San Francisco, California, USA


DNLI $29.29 -8.81% $(2.83)

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