Denali Therapeutics (DNLI) investor relations material

Company overview and technology platform

• Focused on crossing the blood-brain barrier and treating neurodegeneration using transport vehicle (TV) technology, which enables delivery of enzymes, oligonucleotides, and antibodies to the brain and other tissues.

• TV technology is modular, using Fc-engineered antibodies to bind transferrin receptor, allowing broad application across multiple diseases.

• Lead program in Hunter syndrome has achieved both brain delivery and biomarker evidence of halted neurodegeneration.

• BLA filed for lead asset in Hunter syndrome, with active FDA engagement and additional programs advancing in Alzheimer's and other indications.

Clinical progress and data highlights

• In Hunter syndrome, TV platform normalized heparan sulfate in CSF and urine, corrected lysosomal biomarkers, and improved cognition, behavior, and hearing.

• Robust reductions in biomarkers observed even in patients previously treated with gene therapy, demonstrating whole-body and brain efficacy.

• Majority of patients switched from standard of care to TV for better outcomes; over 90% reduction in CSF biomarkers achieved.

• Sanfilippo syndrome program (DNL126) shows similar biomarker normalization, with rapid disease progression and no current standard of care.

Regulatory and commercial strategy

• Lead asset under FDA priority review for accelerated approval, with a PDUFA date in January 2026.

• Commercial strategy targets centers of excellence and emphasizes patient services and support for switching from standard of care.

• Strong overlap in clinical and commercial teams for Hunter and Sanfilippo programs, leveraging established relationships with centers and FDA reviewers.

• Engaged FDA review teams, rapid BLA submission process, and alignment with recent rare disease regulatory guidance.