Denali Therapeutics (DNLI) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Strategic platform and portfolio overview

• Validated Transport Vehicle platform enables delivery of large molecules across the blood-brain barrier, opening new treatment opportunities for neurodegenerative and lysosomal storage diseases.

• Portfolio divided into two peaks: Peak I (clinical stage, three large molecule and three small molecule programs) and Peak II (preclinical, five programs targeting larger indications like Alzheimer's and Parkinson's).

• Peak II includes two Alzheimer's programs (tau ASO and Abeta antibody), an alpha-synuclein ASO, and two enzyme replacement therapies.

• Enzyme replacement therapy franchise seen as a solid core business, providing confidence to tackle larger neurodegenerative indications.

• Prioritization is based on resource allocation and risk, with a focus on following genetic links in disease selection.

Clinical program updates and regulatory pathways

• DNL310 (Hunter syndrome) has a direct path to accelerated approval after recent FDA discussions, with heparan sulfate reduction as the key endpoint.

• Normalization of heparan sulfate is sustained for over two years, followed by reduction in neurofilament, indicating halted neurodegeneration.

• MPS IIIA (DNL126) program is in the FDA's START pilot, aiming for a faster path to approval by leveraging experience from DNL310.

• Phase I/II COMPASS trial for DNL310 uses co-primary endpoints: heparan sulfate reduction at 24 weeks and Vineland Adaptive Behavior score at two years.

• Data for MPS IIIA expected in the second half of the year, with focus on heparan sulfate reduction and safety.

Commercialization, manufacturing, and market strategy

• Plans to commercialize in the U.S. and major European countries, with distributors for the rest of the world; building a European team and Zurich office.

• Hunter syndrome patient population is well-identified, with about 2,000 patients on drug worldwide; newborn screening may expand this.

• Manufacturing costs are significant; a new clinical manufacturing facility in Utah is expected to come online in 6–12 months to reduce costs.

• All Hunter syndrome patients, regardless of neuronopathic status, are targeted for treatment due to CNS involvement in all cases.

• Pricing for DNL310 will be based on clinical benefit and economic considerations, but no specifics yet.