Denali Therapeutics (DNLI) investor relations material

Regulatory and clinical development updates

• Awaiting an FDA decision for tividenofusp alfa in Hunter syndrome, with a PDUFA date set for April 5th; labeling discussions and post-marketing commitments are ongoing.

• The BLA submission for tividenofusp alfa followed positive biomarker data, showing normalization of heparan sulfate and NfL in treated patients, supporting the use of biomarkers as surrogate endpoints.

• A minor review delay was caused by a third-party molecular weight miscalculation, quickly resolved, with overall constructive FDA engagement.

• The COMPASS confirmatory trial supports the clinical package, with long-term data from up to 4-5 years of patient treatment.

• The regulatory environment for rare diseases is evolving, with a high bar set for biomarker-driven approvals.

Commercial strategy and market positioning

• Commercial infrastructure, including field, payer, and medical science liaison teams, was established in anticipation of approval.

• The launch strategy focuses on switching patients from the current standard of care, Elaprase, to tividenofusp alfa, leveraging superior biomarker outcomes.

• Distribution and patient services are in place to support reimbursement and access, with strong engagement from both physicians and patient communities.

• Newborn screening adoption is increasing, with 13 states now screening for Hunter syndrome, expected to drive earlier diagnosis and treatment.

• The Royalty Pharma deal and recent equity financing extend financial runway through 2028, supporting commercialization and pipeline expansion.

Pipeline and platform expansion

• Sanfilippo syndrome (DNL126) program shows robust biomarker and liver volume improvements; key efficacy cohorts are fully enrolled, with a pivotal data cut expected in September for BLA filing.

• Commercial launch for DNL126 will leverage existing infrastructure, maximizing brand margins and operational efficiency.

• Pompe disease program (ETV:GAA) will soon begin dosing, aiming for improved muscle and brain delivery; data expected in 2027.

• Alzheimer's programs targeting MAPT (tau) and Abeta are advancing, with clinical studies starting this year and data anticipated in 2027.

• LRRK2 inhibitor for Parkinson's, in partnership with Biogen, will have a midyear data readout; BEACON study enrollment is progressing rapidly.