Denali Therapeutics (DNLI) investor relations material

Strategic vision and platform innovation

• Focus on transforming treatment for serious diseases by delivering biotherapeutics to the whole body, including the brain, using the proprietary TransportVehicle (TV) platform.

• TV platform enables efficient delivery of enzymes, oligos, and antibodies across the blood-brain barrier (BBB) via transferrin receptor-mediated transcytosis.

• Platform demonstrates modularity, optimized brain uptake, safety, and high-fidelity architecture, supporting a broad therapeutic pipeline.

• Over 350 patents, 20+ high-impact publications, and more than 200 patients dosed validate the platform's leadership.

Product and pipeline highlights

• AVLAYAH (tividenofusp alfa-eknm) is the first FDA-approved enzyme replacement therapy to cross the BBB, targeting neurologic manifestations of Hunter syndrome.

• Robust pipeline includes 7 clinical programs spanning rare genetic and common neurodegenerative diseases, with a market opportunity exceeding $10B.

• ETV franchise addresses lysosomal storage disorders (LSDs) with multiple candidates in clinical and preclinical stages, aiming to treat both CNS and peripheral symptoms.

• Alzheimer’s and Parkinson’s programs leverage TV technology for improved brain delivery and efficacy, with initial clinical data expected in 2027.

Clinical and commercial execution

• AVLAYAH demonstrated significant reductions in CNS and peripheral biomarkers, improvements in adaptive behavior, cognition, and hearing in MPS II patients.

• Safety profile of AVLAYAH is consistent with established ERTs, with infusion-related reactions as the most common adverse event, decreasing over time.

• Strong launch momentum for AVLAYAH, with >50% payer coverage, $3.6M net revenue in Q2 2026, and projected $10–12M in Q3 2026.

• DNL126 (ETV:SGSH) for MPS IIIA achieved biomarker proof-of-concept, with 80% mean reduction in CSF HS and normalization in some participants; BLA filing for accelerated approval planned for 2027.