Denali(DNLI) ZACKS·2025-01-07 20:16Core Findings - Denali Therapeutics Inc (DNLI) announced disappointing top-line results from the phase II/III HEALEY ALS Platform Trial for its pipeline candidate DNL343, which failed to meet the primary endpoint of slowing disease progression compared to placebo [1][3][4] - DNL343, a novel small molecule targeting eIF2B, was well tolerated but did not show statistically significant differences in key secondary endpoints measuring muscle strength and respiratory function at week 24 [4][5] - The HEALEY ALS Platform Trial involved 186 participants receiving DNL343 and 139 receiving placebo, with ALS affecting approximately 30,000 people in the US and 500,000 worldwide [3] Stock Performance - DNLI shares declined 6.5% over the past six months, slightly underperforming the industry's 6.4% decline [2] Pipeline Updates - Denali and partner Sanofi discontinued the development of SAR443820/DNL788 for multiple sclerosis after the phase II K2 study failed to meet primary and key secondary endpoints [6][8] - The companies are co-developing SAR443122/DNL758 (eclitasertib) for ulcerative colitis, currently in phase II studies [8] - Denali's wholly owned program, DNL310 (tividenofusp alfa), is in development for MPS II (Hunter syndrome) [9] - BIIB122 (DNL151), an LRRK2 inhibitor for Parkinson's disease, is being evaluated in a global phase IIa study (BEACON) and a phase IIb study (LUMA) in collaboration with Biogen [9][10][11] Future Plans - Denali will report additional data from the HEALEY ALS Platform Trial in 2025, including neurofilament light (NfL) and other fluid biomarkers, subgroup analyses, and extended findings from the active treatment extension period [5] - The company will evaluate the data before determining next steps for DNL343 [5] Industry Comparison - Immunocore Holdings plc (IMCR), a Zacks Rank 1 (Strong Buy) stock in the biotech sector, has seen narrowing loss per share estimates for 2024 and 2025, with an average earnings surprise of 25.57% in the trailing four quarters [12][13]