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

Strategic platform and pipeline overview

• Validated Transport Vehicle platform enables delivery of large molecules across the blood-brain barrier, supporting a broad portfolio for neurodegenerative and lysosomal storage diseases.

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

• Prioritization in Peak II focuses on three neurodegenerative programs (two for Alzheimer's, one for Parkinson's) and two enzyme replacement therapies, leveraging established biology and risk diversification.

• Enzyme replacement therapy remains a core business, with confidence in expanding to more complex indications as field data improves.

DNL310 Hunter syndrome program and regulatory progress

• Recent FDA discussions have enabled a direct path to accelerated approval for DNL310, marking a major inflection point for the portfolio.

• Accelerated approval is based on normalization of heparan sulfate, a well-established biomarker, with sustained reductions observed for over two years and subsequent neurofilament reduction.

• Clinical data show normalization of neurofilament in all age groups, correlating with halted neurodegeneration and improvements in objective endpoints like hearing.

• Commercial strategy targets the U.S. and major European markets directly, with distributors for other regions; newborn screening may expand the patient base.

• Manufacturing costs are significant, but a new Utah facility is expected to reduce costs and improve margins within 6–12 months.

MPS IIIA (DNL126) and future development

• MPS IIIA program leverages experience from DNL310, with the FDA's START program supporting rapid development and approval for rare diseases.

• Phase I/II trial is open-label, dose-ranging, and focuses on heparan sulfate reduction and safety; expansion is considered to support accelerated approval.

• Data from this program are expected in the second half of the year.

• Disease prevalence is similar to Hunter syndrome, with primary focus on heparan sulfate as a biomarker.