DNL343

IGM Biosciences halts development of imvotamab and IGM-2644 due to disappointing Phase I results, leading to a 73% workforce reduction. The company, with $183.8M in cash, seeks alternative cost recovery methods. Stock dropped 70%. Denali Therapeutics and XBiotech also face trial setbacks.

Denali Therapeutics received FDA Breakthrough Therapy Designation for tividenofusp alfa (DNL310) for Hunter syndrome, planning a Biologics License Application by early 2025. Despite a Phase 2/3 trial miss for ALS treatment DNL343, Denali's neurodegenerative disease platform and LRRK2 inhibitor BIIB122 for Parkinson’s show promise. Analysts remain optimistic, with upgrades and a focus on the company's innovative transport vehicle technology.

Biogen's LUMA study aims to enroll 640 early-stage Parkinson's patients, including those with LRRK2 mutations. Denali's DNL343, tested in the HEALEY ALS trial, failed to meet primary and secondary efficacy endpoints for ALS treatment. Sanofi discontinued SAR443820/DNL788 development for ALS and MS after unsuccessful phase II trials. Denali holds a Zacks Rank #3, while Halozyme Therapeutics, with a Zacks Rank #1, shows promising earnings estimates.

A phase 2/3 trial for DNL343, an eIF2B agonist targeting ALS, failed to meet its primary endpoint of slowing disease progression at week 24. Secondary endpoints also showed no significant difference. Despite this, DNL343 was safe and well-tolerated. Further data analysis is planned to guide future ALS research.

Stifel analysts maintain a Buy rating on Denali Therapeutics with a $37 target, following FDA's Breakthrough Therapy Designation for DNL310 for Hunter Syndrome. Despite negative earnings, the stock is seen as undervalued, with potential for accelerated approval by 2025. Denali's strong financials and promising treatments for Hunter and Sanfilippo Syndromes, estimated at over $1 billion market, support optimism despite recent trial setbacks.

Tenvie Therapeutics, backed by ARCH Venture Partners, F-Prime Capital, and Mubadala Capital, launches with $200M and Denali Therapeutics assets to develop small molecules for neurological, cardiometabolic, and ophthalmic diseases. Its pipeline includes four neurology candidates. Leadership includes former Denali executives.

Denali Therapeutics' Phase II/III trial of DNL343 for ALS did not meet its primary endpoint, showing no significant difference in disease severity or survival rates compared to placebo at 24 weeks. The therapy was safe and well-tolerated. Further analyses, including NfL biomarkers and subgroup data, are anticipated later this year.

Denali Therapeutics Inc. reported disappointing results from its phase II/III HEALEY ALS Platform Trial for DNL343, failing to meet primary and secondary endpoints in slowing ALS progression. Despite being well tolerated, the study did not show efficacy over placebo. Denali plans further data analysis and reports by 2025. Additionally, Sanofi discontinued a related MS study for SAR443820/DNL788, previously halted for ALS treatment.

DNL343, an investigational eIF2B agonist for ALS, did not meet its primary endpoint in the HEALEY-ALS trial, showing no significant difference from placebo in overall function, survival, muscle strength, or respiratory function at 24 weeks. Further analyses are expected by late 2025. The treatment was safe and well-tolerated.