Denali Therapeutics (DNLI) 44th Annual J.P. Morgan Healthcare Conference summary

Strategic vision and technology platform

• Focused on delivering biotherapeutics to the brain and body using the TransportVehicle platform, leveraging transferrin receptor-mediated delivery for broad tissue access and systemic delivery of enzymes, oligonucleotides, and antibodies.

• Transitioned from a science-driven to a development and commercial organization, with in-house manufacturing, 520+ employees, and a strong financial position to support growth.

• Platform validated with over 200 subjects dosed, 11,000+ doses administered, and 20+ publications in five years.

• Prioritizes indications with well-understood biology, available biomarkers, and significant unmet need for efficient clinical proof of concept.

• Continues to invest in blood-brain barrier research, with a dedicated team and capital for strategic execution.

Clinical pipeline and program updates

• On the verge of first approval for tividenofusp alfa (tivi/DNL310) in Hunter syndrome, with a PDUFA date set for April 5th after resolving a molecular weight miscalculation.

• Two near-term launches: tividenofusp alfa (DNL310) in 2026 and DNL126 in 2027, targeting lysosomal storage disorders, with additional programs in FTD-GRN, Pompe, and Alzheimer's advancing.

• Expanding clinical programs in rare diseases (Hunter, Sanfilippo, Pompe) and neurodegenerative diseases (Alzheimer's, FTD), with multiple readouts and filings expected through 2027.

• SGSH for Sanfilippo selected for the FDA's START program, aiming for accelerated approval and leveraging learnings from the Hunter program to reduce timeline and cost.

• DNL593 (PTV-Progranulin) for FTD has completed phase I-II enrollment, with biomarker data expected by year-end.

Technology differentiation and clinical data

• TransportVehicle platform enables even brain distribution and enhanced delivery to other tissues, outperforming standard antibodies in preclinical models.

• Demonstrated robust normalization of disease biomarkers and clinical improvements in cognition, behavior, and hearing in Hunter syndrome.

• Safety profile shows declining infusion reactions and immune-silent engineering, with over 11,000 doses administered across programs.

• Comparative studies show superior brain uptake and molecular stability versus other BBB technologies, with reduced ARIA risk in Alzheimer's models.

• Platform modularity allows delivery of enzymes, antibodies, and oligonucleotides, with first oligonucleotide program entering the clinic.