Denali Therapeutics (DNLI) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Strategic vision and platform development

• Focused on defeating neurodegeneration and engineering medicines to cross the blood-brain barrier, with a decade of progress leading to anticipated first product approval using proprietary technology.

• Established leadership in blood-brain barrier engineering, enabling delivery of multiple therapeutic modalities to the brain.

• Expanded enzyme transport vehicle platform to target additional diseases and modalities, including oligo and antibody transport vehicles.

• Oligo transport vehicle (OTV) platform advances antisense oligo delivery to the brain, with MAPT and SNCA as lead targets for Alzheimer's and Parkinson's.

• Capital allocation prioritizes near-term commercial opportunities and internal manufacturing to reduce costs and accelerate development.

DNL310 (tividenofusp alfa) for Hunter syndrome

• Phase II/III COMPASS study is enrolling, comparing tividenofusp alfa to idursulfase in neuronopathic Hunter syndrome.

• Accelerated approval filing planned for early 2025, following FDA alignment on heparan sulfate as a surrogate biomarker.

• Data show >90% reduction in CSF heparan sulfate and normalization of NfL, with improvements in cognition and peripheral endpoints.

• Therapy aims to treat both body and brain, addressing limitations of current standard of care.

DNL126 for Sanfilippo syndrome (MPS IIIA)

• Engineered enzyme uses transport vehicle technology to cross the blood-brain barrier, targeting neurological symptoms.

• Phase I/II study design being expanded to support accelerated approval, with interim biomarker and safety data expected by year-end.

• Heparan sulfate accepted as a surrogate biomarker, guiding regulatory strategy.

• START designation enables ongoing dialogue with FDA to accelerate development.