Denali Therapeutics (DNLI) investor relations material

Recent milestones and platform overview

• Achieved FDA approval for AVLAYAH, the first medicine to cross the blood-brain barrier for neurologic and whole-body treatment in Hunter syndrome, marking a major advancement after 20 years of research.

• Developed the Transport Vehicle platform, enabling biologics to cross the blood-brain barrier using transferrin receptor technology, with enzyme replacement therapy as the initial proof of concept.

• AVLAYAH launch saw rapid uptake, with strong engagement from prescribers and patient enthusiasm, though label currently covers only pediatric and severe neurologic cases (about 70-75% of U.S. patients).

• Ongoing COMPASS phase III head-to-head study versus ELAPRASE aims to expand label to all U.S. patients and support ex-U.S. approvals, with data expected in the second half of 2027.

Pipeline and upcoming catalysts

• Next 6-12 months will be data-rich, with a second BLA filing for Sanfilippo syndrome, ongoing studies in Pompe disease, and a progranulin replacement therapy for FTD dementia.

• Sanfilippo program expects 20-patient data cut in September, aiming for WORLDSymposium presentation in February and BLA filing next year; manufacturing is being onshored for this product.

• Phase III for Sanfilippo is in startup, with potential for open-label design due to lack of standard of care, which may accelerate enrollment and data generation.

• Alzheimer's portfolio advancing with MAPT oligonucleotide (IV/sub-Q) and Abeta antibody using Transport Vehicle technology; Abeta phase I starts in healthy volunteers, focusing on safety and biodistribution.

Differentiation, efficacy, and commercial strategy

• AVLAYAH demonstrates normalization of CSF heparan sulfate and neurofilament, indicating robust CNS and peripheral biomarker improvement versus standard of care.

• Pricing for AVLAYAH is set at a premium ($270,000–$800,000/year depending on patient weight), higher than ELAPRASE, reflecting innovation and broader clinical benefit.

• Early launch metrics show strong interest, especially among patients switching from ELAPRASE, with commercial buildout ongoing and payer policies still being established.

• Sanfilippo market size is similar to Hunter syndrome, but with no current standard of care, representing a significant unmet need and commercial opportunity.