ASN-90

A build-up of the abnormal tau can contribute to Alzheimer’s disease symptoms. Credit: Andrew Brookes via Getty Images. After Eli Lilly and Biogen’s setbacks in developing O-GlaNAcase (OGA) inhibitors for Alzheimer’s disease, Asceneuron has now halted its own Phase II trial of ASN51, its experimental oral OGA inhibitor. The company disclosed the decision in an update to the federal clinical trials database ClinicalTrials.gov , describing it as “strategic” without providing further details. The trial, which kicked off in October 2024, was expected to run for two years. The study (NCT06677203) was set to evaluate two doses of ASN51 against a placebo in 123 patients with early Alzheimer’s, focusing on safety, tolerability, suicide severity assessment through the Columbia-Suicide Severity Rating Scale (C-SSRS), and tau protein levels in cerebrospinal fluid. Asceneuron had previously said that ASN51 could be a disease-modifying therapy, with applications beyond Alzheimer’s in diseases such as Parkinson’s and amyotrophic lateral sclerosis (ALS). The decision to move ASN51 into this Phase II study was supported by a $100m Series C funding round announced in July 2024. The financing was led by Novo Holdings, the controlling shareholder of Novo Nordisk. Novo Holdings’ senior partner for venture investments Naveed Siddiqi described ASN51 as offering “the potential paradigm shift” in Alzheimer’s treatment at the time of the funding round. Asceneuron had already demonstrated in multiple Phase I studies that ASN51 reaches the nervous system and impacts the OGA enzyme. OGA inhibitors have been explored as a potential new class of disease-modifying treatments for Alzheimer’s and other neurodegenerative diseases due to their ability to target tau protein accumulation. Unlike amyloid-targeting therapies – such as Eisai and Biogen’s Leqembi (lecanemab) – that have dominated Alzheimer’s drug development, OGA inhibitors aim to slow disease progression by preventing the buildup of toxic tau aggregates in the brain. This termination follows setbacks for other OGA inhibitors in development. In August 2024, Eli Lilly disclosed that its OGA inhibitor, LY3372689, failed to meet the primary endpoint in a Phase II trial (NCT05063539) for early symptomatic Alzheimer’s. The study did not show a statistically significant benefit in slowing disease progression as measured by the integrated Alzheimer’s Disease Rating Scale (iADRS). Lilly also previously abandoned its antibody-based tau inhibitor zagotenemab in 2021 while Roche discontinued the development of semorinemab in January 2024. Last month, Biogen discontinued an early-stage OGA inhibitor programme, BIIB113. Beyond ASN51, Asceneuron has another OGA inhibitor, ASN90, which it licensed to Ferrer in February 2023. ASN90 is currently in a Phase II trial (NCT06355531) for progressive supranuclear palsy, a rare tau-related neurodegenerative disorder.