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, targeting diseases like Alzheimer's, Parkinson's, and ALS.

• Developed enzyme, oligo, and antibody transport vehicle platforms to deliver therapeutics into the brain.

• Positioned as a leader in blood-brain barrier engineering, aiming for multiple modalities and broad applicability.

• Oligo transport vehicle (OTV) platform targets tau and alpha-synuclein for Alzheimer's and Parkinson's, with IND-enabling programs underway.

• Clinical manufacturing facility coming online in 2024, expected to reduce manufacturing costs by 40% per enzyme.

Key clinical programs and regulatory progress

• DNL310 (tividenofusp alfa) for Hunter syndrome is enrolling in the phase II/III COMPASS study, with plans to file for accelerated approval in early 2025.

• DNL310 shows >90% reduction in CSF heparan sulfate and normalization of NfL, with improvements in cognition and peripheral endpoints.

• DNL126 for Sanfilippo syndrome leverages similar technology, with phase I/II interim biomarker and safety data expected by year-end; study design expanded for accelerated approval pathway.

• Biomarker heparan sulfate now accepted by FDA as a surrogate reasonably likely to predict clinical benefit, supporting accelerated approval strategies.

Pipeline expansion and partnerships

• ATV:Aβ program for Alzheimer's is advancing with both TFR and CD98 approaches, aiming for robust plaque reduction with less ARIA; head-to-head comparison ongoing.

• Biogen terminated its license to ATV:Aβ, but collaboration continues on LRRK2 inhibitor (BIIB122) for Parkinson's, with a large phase II/III study ongoing.

• Sanofi partnership explores RIPK1 inhibition in MS, ALS, and ulcerative colitis; Sanofi leads clinical development and indication selection.

• DNL343 in ALS is part of the Healy platform trial, with 240 patients; early clinical efficacy will determine further investment.