Alector Discontinues Dementia Drug Development, Announces Restructuring

Alector, a clinical-stage biopharmaceutical company, has announced the discontinuation of its investigational antibody latozinemab following disappointing results from the Phase III INFRONT-3 trial. The drug, which was being developed for a genetic form of frontotemporal dementia (FTD), failed to demonstrate clinical benefit in patients with FTD caused by progranulin gene mutations.

Trial Results and Drug Discontinuation

The INFRONT-3 trial revealed that while latozinemab had a significant effect on progranulin, a biomarker linked to FTD, it did not significantly slow disease progression compared to placebo. The drug also missed key secondary endpoints, showing no treatment effect on volumetric magnetic resonance imaging outcomes and other fluid biomarker concentrations.

This setback represents Alector's second failed neurodegenerative asset in a year, following the unsuccessful development of an AbbVie-partnered asset for Alzheimer's disease in late 2024. The company has decided to halt the planned open-label extension portion of the INFRONT-3 trial and cancel a continuation study of latozinemab.

Corporate Restructuring and Leadership Changes

In response to the trial failure, Alector has announced a significant restructuring of its operations:

• Approximately 49% of the workforce will be laid off, potentially affecting around 116 employees based on the company's reported 238 full-time staff at the end of 2024.
• Sara Kenkare-Mitra, Alector's president and R&D head, will step down from her position effective December 22, 2025.
• The company will conduct a strategic review of its business to maximize resources.

Financial Position and Future Focus

Despite the setback, Alector reports a relatively stable financial position:

• As of September 30, 2025, the company had $291.1 million in cash, cash equivalents, and short-term investments.
• This financial cushion is expected to sustain operations through 2027.

Alector's partnership with GSK, established in 2021 with a $700 million upfront payment, remains ongoing. The collaboration includes the development of AL101, another progranulin modulator currently being assessed in the Phase II PROGRESS-AD trial for early Alzheimer's disease. An independent interim analysis of this trial is scheduled for the first half of 2026.

Moving forward, Alector will focus on its wholly owned assets, including:

• AL137, an anti-amyloid beta antibody for Alzheimer's disease (preclinical stage)
• AL050, an enzyme replacement therapy for Parkinson's disease (preclinical stage)

The company plans to present a detailed analysis of the INFRONT-3 trial data at an upcoming medical meeting, providing further insights into the implications of this development for the field of neurodegenerative disease research.