Denali Therapeutics Inc. (Nasdaq: DNLI) has announced its first quarter 2024 financial results and provided business highlights, including positive clinical updates for its key programs targeting neurodegenerative and lysosomal storage diseases.
Tividenofusp Alfa (DNL310) for MPS II (Hunter Syndrome)
New data from the ongoing Phase 1/2 study of tividenofusp alfa, an Enzyme Transport Vehicle (ETV)-enabled iduronate-2-sulfatase (IDS) replacement therapy for MPS II, were presented at the 20th Annual WORLDSymposiumTM. The data demonstrated sustained normalization of heparan sulfate in cerebrospinal fluid (CSF HS), robust and sustained reductions in biomarkers of lysosomal dysfunction and neuronal damage (NfL), and improvements and stabilization of multiple clinical outcomes measures over two years of treatment.
Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics, stated, "We presented new positive two-year clinical data on tividenofusp alfa in MPS II at WORLDSymposiumTM, and we are encouraged by recent interactions with the FDA about the potential path to patients."
Denali is in continued dialogue with the FDA's Center for Drug Evaluation and Research (CDER) and believes the division may be open to discussing an accelerated path for tividenofusp alfa. The global Phase 2/3 COMPASS study is expected to complete enrollment in 2024.
DNL343 for Amyotrophic Lateral Sclerosis (ALS)
The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH), in collaboration with the Northeast ALS Consortium (NEALS), announced the completion of enrollment in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial. DNL343 is an eIF2B activator in development for the treatment of ALS.
DNL126 for MPS IIIA (Sanfilippo Syndrome Type A)
Denali has initiated dosing in the Phase 1/2 study of DNL126, an ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy for MPS IIIA. Supportive preclinical data were presented at WORLDSymposium™. Phase 1/2 biomarker and safety data are expected by the end of 2024.
Other Program Updates
- SAR443820/DNL788 (Multiple Sclerosis): Sanofi is evaluating SAR443820/DNL788, a CNS-penetrant RIPK1 inhibitor, in a fully enrolled Phase 2 study in participants with MS. Sanofi discontinued development of SAR443820/DNL788 in ALS based on Phase 2 HIMALAYA study results.
- BIIB122/DNL151 (Parkinson’s Disease): Denali plans to initiate a global Phase 2a study of BIIB122/DNL151, a LRRK2 inhibitor, to evaluate safety and biomarkers in participants with Parkinson’s disease and confirmed pathogenic variants of LRRK2. Biogen is conducting the ongoing global Phase 2b LUMA study of BIIB122 in participants with early-stage Parkinson’s disease.
- Eclitasertib (SAR443122/DNL758) (Ulcerative Colitis): Sanofi is conducting the ongoing Phase 2 study of SAR443122/DNL758, a peripheral RIPK1 inhibitor, in participants with UC.
- TAK-594/DNL593 (Frontotemporal Dementia): Denali has voluntarily paused the DNL593 Phase 1/2 study in participants with FTD-GRN to implement protocol modifications and expects the study to resume this year.
Financial Highlights
Denali reported a net loss of $101.8 million for the quarter ended March 31, 2024, compared to a net loss of $109.8 million for the quarter ended March 31, 2023. The company's cash, cash equivalents, and marketable securities were approximately $1.43 billion as of March 31, 2024. In February, Denali completed a private investment in public equity (PIPE) financing with gross proceeds of $500 million.
