Denali Therapeutics (DNLI) 12th Annual Cantor Fitzgerald Global Healthcare Conference summary

Company evolution and strategic focus

• Four pillars: first product launch (AVYLAH), validated platform, broad pipeline, and strong capital position with $1.1B cash to fund operations into 2029.

• Portfolio includes enzyme replacement therapies, Alzheimer's programs, and five additional clinical-stage programs with key data readouts expected in 2027.

• AVYLAH launch validates the platform and marks transition from discovery to delivering medicines to patients.

• Enzyme franchise seen as a $7B–$9B peak sales opportunity across multiple indications, with profitability targeted through the franchise rather than a single product.

• Alzheimer's programs offer significant optionality, with biomarker readouts anticipated in 2027.

AVYLAH launch and market dynamics

• AVYLAH approved for pediatric Hunter syndrome patients with neurologic manifestations, covering about 375 of 500 U.S. patients.

• Annual U.S. incidence is about 30 new Hunter patients; nearly all eligible patients are currently on Elaprase, except those in palliative care.

• Launch revenue guidance: $3.6M in Q2, targeting $10M–$12M in Q3, driven by new patient starts and dose escalation.

• Early payer coverage includes Medicaid in 14 states, with an expected 50/50 split between private and Medicaid payers as launch matures.

• Real-world data and ongoing clinical trials will inform long-term benefits, including potential improvements in cardiac outcomes and overall survival.

Pipeline progress and clinical development

• COMPASS phase III trial for AVYLAH is fully enrolled, aiming to expand the label to adults, with primary endpoints in cognition and behavior; data expected mid-2028.

• Sanfilippo (MPS IIIA) program progressing toward BLA filing in 2027, with manufacturing being the rate-limiting step; first product to be launched from in-house facility.

• Sanfilippo trial design differs from AVYLAH, reflecting ethical and regulatory considerations; no placebo control, delayed start for one arm.

• Hunter program is expected to de-risk other enzyme replacement programs in the pipeline.

• Pompe and other enzyme programs leverage transport vehicle technology, with robust preclinical data supporting muscle uptake.