Denali Therapeutics Inc. is a American biotechnology company headquartered in South San Francisco, California, focused on developing therapies for neurodegenerative diseases. Founded in 2013 as a spinout from Genentech, Denali is a leader in LRRK2 inhibitors for Parkinson's disease and has a broad pipeline in Alzheimer's disease, ALS, and other neurological conditions.
| Attribute | Details |
|-----------|---------|
| Ticker | NASDAQ: DNLI |
| Headquarters | South San Francisco, California, USA |
| Founded | 2013 |
| CEO | Carole Ho |
| Employees | ~450 |
| Market Cap | ~$2.5 billion (2024) |
| Drug |
Mechanism |
Phase |
Indication |
| DNL151 (BIIB122) |
LRRK2 inhibitor |
Phase 2b |
Parkinson's disease |
| DNL151 |
LRRK2 inhibitor |
Phase 1 (Japan) |
Parkinson's disease |
| DNL261 |
LRRK2 inhibitor |
Phase 1 |
Parkinson's disease |
- Mechanism: LRRK2 kinase inhibitor
- Target: Leucine-rich repeat kinase 2 (LRRK2)
- Phase: Phase 2b (LUMA study)
- Partner: Biogen (co-development and co-commercialization)
- Status: Recruiting
- Clinical Trials: LUMA, NCT03976375
- Rationale: LRRK2 mutations are a major genetic risk factor for Parkinson's disease; inhibition may slow disease progression
- Mechanism: eIF2B activator
- Target: Integrated stress response
- Phase: Phase 1
- Rationale: Modulate cellular stress response in neurodegeneration
| Drug |
Mechanism |
Phase |
Indication |
| DNL919 (ARCAM-1) |
TREM2](/proteins/trem2) agonist |
Preclinical |
AD |
| DNL593 |
- |
Discovery |
AD |
| DNL788 |
- |
Discovery |
AD |
- Mechanism: TREM2 agonist antibody
- Target: TREM2 (Triggering Receptor Expressed on Myeloid Cells 2)
- Phase: Preclinical
- Rationale: TREM2 variants are genetic risk factors for Alzheimer's; agonism may enhance microglial function
| Drug |
Mechanism |
Phase |
| DNL788 |
- |
Phase 1 (planned) |
| DNL558 |
- |
Discovery |
| Drug |
Mechanism |
Phase |
| DNL310 (ENHANZE) |
Enzyme replacement (IDS) |
Phase 2/3 |
- Mechanism: Iduronate-2-sulfatase (IDS) enzyme with Brain Transport Vehicle (TVB)
- Target: Central nervous system delivery of enzyme
- Phase: Phase 2/3
- Partner: Takeda (license agreement)
- Status: Recruiting
Denali's proprietary Brain Transport Vehicle enables delivery of large therapeutic molecules across the blood-brain barrier (BBB).
- Application: Used in DNL310 (Hunter syndrome) and other CNS programs
- Mechanism: Transcytosis via receptor-mediated transport
- Design: Highly brain-penetrant, selective LRRK2 inhibitors
- Advantage: Good CNS penetration, safety profile suitable for chronic dosing
- Approach: monoclonal antibodies that activate TREM2 signaling
- Rationale: Enhance microglial function in Alzheimer's disease
- Scope: Co-development and co-commercialization of LRRK2 inhibitor program
- Structure: 50/50 profit sharing in US; Denali leads development, Biogen leads commercialization
- Deal Date: 2020
- Value: $1.1B upfront and milestones
- Scope: License to DNL310 (ENHANZE) for Hunter syndrome
- Structure: Takeda leads commercialization; Denali receives royalties
- Deal Date: 2022
- F-star Therapeutics - Reserved protein platform for TREM2 program
- Various academic collaborations for biomarker development
| Year |
Revenue |
Cash |
Key Programs |
| 2023 |
$67M |
$650M |
LRRK2, DNL310 |
| 2022 |
$50M |
$700M |
LRRK2, DNL310 |
| 2021 |
$25M |
$750M |
LRRK2 |
- Carole Ho - CEO (former Genentech)
- Eric K. Green - Chief Scientific Officer
- William (Bill) J. R. C. Lee - Co-founder and Chairman
¶ Funding and Financial History
- IPO: May 2017 (NASDAQ: DNLI)
- Raised $250 million in initial public offering at $18/share
- Market cap at IPO: approximately $1.8 billion
- Series A: 2015, $50 million (lead investors not disclosed)
- Series B: 2016, $100 million (including Google Ventures, Arrowview Partners)
- Series C: 2017, $150 million (before IPO)
- Biogen: Co-development and co-commercialization agreement for LRRK2 inhibitors (DNL151/BIIB122)
- Deal value: $460 million upfront + $1.1 billion in milestones
- Takeda: Collaboration on blood-brain barrier transport technology (AV-101)
- Genentech: Original founding partnership (founder from Genentech)