Denali Therapeutics (DNLI) investor relations material

Strategic vision and platform evolution

• Expanded focus from neurodegeneration to whole-body biotherapeutics, leveraging the transferrin receptor-enabled TV platform for enhanced delivery to brain, muscle, and other tissues, enabling new therapeutic areas.

• TV platform includes Enzyme TV (ETV), Antibody TV (ATV), and Oligonucleotide TV (OTV), is modular, engineered for optimal brain uptake, safety, and manufacturability, with over 11,000 doses administered and more than 350 patents/applications.

• D3 strategy (discover, develop, deliver) guides the next phase, with three-year goals: build two brands (TIVI and DNL126), achieve five clinical proof-of-concept milestones, and advance four to six new clinical-stage programs.

• TV platform is the most clinically validated BBB technology, with five clinical-stage programs, more than 10 preclinical programs, and demonstrated ability to correct neurodegeneration.

• Integrated manufacturing and commercial capabilities established to accelerate development, reduce costs, and support global launches.

Pipeline, clinical progress, and near-term launches

• Two near-term launches: tividenofusp alfa (TIVI/DNL310) for Hunter syndrome (MPS II) in 2026 and DNL126 for MPS IIIA in 2027, establishing the ETV franchise.

• TIVI is under FDA review with a PDUFA date in April 2026, late-cycle label negotiations ongoing, and a $275M deal with Royalty Pharma contingent on regulatory milestones.

• DNL126 achieved biomarker proof-of-concept in MPS IIIA, with Phase 1/2 enrollment completed, Phase 3 protocol in development, and BLA submission expected in 2027.

• Additional programs in Alzheimer's (ATV Aβ/DNL921, OTV MAPT/DNL628), FTD-GRN (DNL593), Pompe (DNL952/ETV:GAA), and Parkinson's are advancing, with multiple clinical and preclinical milestones expected by 2026–2027.

• Pompe program (ETV GAA) is on clinical hold due to preclinical hypersensitivity findings; protocol amendments have been submitted to address FDA concerns.

Commercialization and market opportunity

• ETV franchise targets lysosomal storage disorders with a combined market opportunity exceeding $1B for the first two launches and $5B+ total.

• TIVI launch strategy targets both brain and peripheral manifestations of Hunter syndrome, aiming for broad indication and rapid adoption, with a focus on patient and physician engagement, payer education, and streamlined reimbursement.

• U.S. market for TIVI estimated at 400–500 patients, with 50% covered by Medicaid and 50% by commercial payers; global expansion expected to access 60% of addressable market pre-EU launch.

• Pricing strategy aims for a premium to standard of care, reflecting clinical and societal value while ensuring broad access and affordability.

• Commercial team and field force are in place, leveraging established relationships with centers of excellence and geneticists, with synergies expected between TIVI and DNL126 launches.