Denali Therapeutics (DNLI) investor relations material

Commercial launch and product pipeline

• AVLAYAH received FDA approval for Hunter syndrome, marking the first commercial launch from the Transport Vehicle platform and strong early enthusiasm from the field, with most initial patients switching from prior standard of care.

• Pricing reflects clinical differentiation, with no payer pushback and a standard weight-based model; revenue inflection is expected in 2027 as payer policies settle, with 2026 as a setup year.

• International expansion is a priority, with European filing planned after COMPASS study data in 2027; accelerated or conditional approvals may allow earlier access in some markets.

• Label expansion to adults is targeted via the COMPASS study, with data expected to support both European approval and broader U.S. labeling.

Research and clinical development

• The next enzyme replacement therapy for Sanfilippo syndrome will complete its 49-week study in September, with BLA filing targeted for 2027; commercial manufacturing will be in-house.

• Pompe disease program is enrolling, with 2027 data expected; Transport Vehicle technology aims to improve muscle and CNS delivery over standard therapies.

• Progranulin program for frontotemporal dementia continues after Takeda ended its collaboration; data expected by year-end, focusing on both proximal and distal biomarkers.

• Two Alzheimer’s programs—an oligonucleotide targeting tau and an A-beta antibody—are progressing, with first biomarker data expected in 2027; both leverage the Transport Vehicle for improved brain delivery.

Regulatory and market dynamics

• Engagement with the FDA on Sanfilippo syndrome remains consistent, with CSF heparan sulfate accepted as a surrogate endpoint; early diagnosis and newborn screening are emphasized due to rapid disease progression.

• No standard of care exists for Sanfilippo, so launch dynamics will differ from Hunter syndrome, with a focus on early patient identification.

• The combination of AVLAYAH and DNL126 is projected as a billion-dollar-plus global opportunity.