Denali Therapeutics (DNLI) Jefferies London Healthcare Conference 2024 summary

Strategic focus and technology overview

• Emphasis on crossing the blood-brain barrier and targeting neurodegeneration, with validated data showing successful delivery in humans.

• Portfolio split between large molecule (enzyme and antibody transport vehicles) and small molecule programs, with near-term value drivers in rare lysosomal storage diseases and Alzheimer's.

• Proprietary technology uses engineered Fc portions of IgG for improved brain delivery, enabling modular transport of various therapeutic cargos.

• Biomarkers are now central to regulatory strategy, serving as surrogate endpoints for accelerated approval.

• Ongoing expansion into oligonucleotide transport, aiming for systemic delivery to the brain.

Clinical pipeline and regulatory progress

• Hunter syndrome program shows normalization of key biomarkers and neurofilament, with BLA filing planned for early next year.

• Sanfilippo (SGSH) program expanded to 20 patients, aiming for accelerated approval with FDA START designation and phase III design underway.

• Progranulin program demonstrates strong biomarker response in healthy volunteers; proof-of-concept trial ongoing.

• Two additional enzyme programs in IND-enabling studies, with one IND filing expected mid next year.

• Regulatory landscape is shifting, with FDA increasingly accepting biomarkers as surrogate endpoints, especially for MPS disorders.

Small molecule and antibody programs

• Discovery efforts now focused on blood-brain barrier technologies, with legacy small molecule programs still active.

• eIF2B agonist program completed enrollment in HEALEY platform study; awaiting top-line data.

• LRRK2 inhibitor program in large phase II-B (LUMA) and phase II-A (BEACON) studies, targeting Parkinson's disease.

• Lead Alzheimer's antibody engineered for immune silence at transferrin receptor, showing superior plaque reduction and reduced ARIA risk in preclinical models.

• Plan to enter clinic with Alzheimer's antibody program within 6-12 months.