Denali Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Updates

Denali Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Updates

South San Francisco, CA, February 27, 2024: Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases, today reported financial results for the fourth quarter and year ended December 31, 2023, and provided business highlights.

"2023 was a year of significant progress across our broad therapeutic portfolio and further clinical validation of our BBB-crossing Transport Vehicle (TV) platform," said Ryan Watts, Ph.D., Chief Executive Officer of Denali. "In 2024, we expect to complete enrollment of our late-stage trials in MPS II and ALS as we establish commercial readiness for our product candidates in our first peak of programs. In addition, we are well positioned to expand our TV-enabled portfolio to address large neurodegenerative diseases with TV-enabled enzymes, antibodies, and oligonucleotides."

Fourth Quarter 2023 and Recent Program Updates Late-stage and mid-stage clinical programs

• Tividenofusp alfa (DNL310): Enzyme Transport Vehicle (ETV)-enabled, iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome)
• Presented additional interim data from the open-label, single-arm Phase 1/2 study of DNL310 at the 2024 WORLDSymposium™. Data out to 104 weeks showed additional improvement and stabilization in multiple measures of clinical outcomes, including those of adaptive behavior, cognition, hearing, and growth trajectory. In addition, robust and sustained responses in biomarkers of neuronal health (e.g., CSF heparan sulfate, neurofilament light [NfL]) and peripheral activity (e.g., urine heparan sulfate and dermatan sulfate) were observed. DNL310 continued to be generally well tolerated.
• Participated in the Reagan-Udall Foundation for the Food and Drug Administration (FDA) workshop that brought together FDA representatives, patient advocates, clinical and basic science researchers, and industry to explore a case study of CSF heparan sulfate as a relevant substrate biomarker to support accelerated approval in neuronopathic mucopolysaccharidoses (MPS).
• Enrollment continues in the global Phase 2/3 COMPASS study and is expected to be completed in 2024.

DNL343: eIF2B activator in development for the treatment of ALS

• Enrollment continues in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial and is expected to be completed in 2024.

SAR443820/DNL788: CNS-penetrant RIPK1 inhibitor in development for the treatment of multiple sclerosis (MS)

• As previously announced, Sanofi informed Denali that the Phase 2 HIMALAYA study evaluating SAR443820/DNL788 in participants with ALS did not meet the primary endpoint of change in ALS Functional Rating Scale-Revised (ALSFRS-R). Sanofi intends to present the detailed efficacy and safety results of the ALS Phase 2 HIMALAYA study at a future scientific forum.
• Sanofi is evaluating SAR443820/DNL788 in another Phase 2 clinical trial in participants with MS, and the outcome of HIMALAYA study has no impact on the ongoing MS study.

BIIB122/DNL151: LRRK2 inhibitor in development for the treatment of Parkinson's disease (PD)

• Today Denali also announced the execution of a Collaboration and Development Funding Agreement in January 2024 with a third party related to a global Phase 2a study of BIIB122/DNL151, which Denali plans to solely operationalize to evaluate safety and biomarkers associated with BIIB122 in participants with Parkinson's disease and confirmed pathogenic variants