OGA

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.

A small Swiss biotech has terminated a mid-stage test of a new type of oral drug for people with Alzheimer’s disease, according to the federal clinical trials database. About eight months ago, Asceneuron disclosed a $100 million Series C to advance its O-GlcNAcase (OGA) inhibitor ASN51 into a Phase 2 study. The biotech ran the trial, which was expected to take two years, for less than a month before terminating it, according to the trial’s entry in the database. Asceneuron CEO Barbara Angehrn Pavik declined to provide a reason for the trial termination. In the registry, the biotech cited a “strategic decision.” “We don’t comment on our development plan at this stage,” she said Tuesday in an email to Endpoints News . “Also, we can’t answer any other questions that you might have.” Shortly after Asceneuron’s fundraise in July, Eli Lilly — its main competitor — said a drug in the same class failed a Phase 2 test. Then, last month, Biogen scrapped an early-stage drug in the same class. All three companies were trying to develop OGA inhibitors, which they believed would slow or curb the buildup of tau in patients with Alzheimer’s. If too much tau accumulates, the protein can damage neurons and have neurodegenerative effects. Another protein, amyloid, has been the target of a trio of FDA-approved Alzheimer’s medicines in recent years. The class of OGA inhibitors in development has been viewed as one of the next frontiers in the decadeslong battle to come up with disease-modifying treatments for Alzheimer’s. The amyloid-targeted treatments developed by Lilly and Biogen’s partner Eisai have been shown to slow Alzheimer’s, but only modestly , and that has left the door open for better medicines. Asceneuron’s Series C was expected to fully fund the now-terminated trial. At the time it was announced, Asceneuron board member Naveed Siddiqi told Endpoints the funding may also progress ASN51 into other indications like Parkinson’s disease and amyotrophic lateral sclerosis. He’s a senior partner on the venture investments team at Novo Holdings, the Series C’s lead investor. The biotech has another OGA inhibitor that it licensed out to Ferrer in early 2023 for undisclosed terms. The candidate, dubbed ASN90, is being tested in a Phase 2 trial as a treatment for progressive supranuclear palsy.

Asceneuron pulled in $100 million in series C funding last summer to advance its lead drug, the oral O-GlcNAcase (OGA) inhibitor ASN5, into Phase II testing for early Alzheimer's disease. That trial, which kicked off in October, has now been shut down.The Swiss neuroscience startup called it a "strategic decision," according to an update on ClinicalTrials.gov this week.The randomised study was investigating two dosage levels of ASN51 oral capsules against placebo in 123 adults with early Alzheimer's disease. The outcomes were focused on safety, tolerability, and suicide severity assessment through the Columbia-Suicide Severity Rating Scale (C-SSRS), as well as tau levels in cerebrospinal fluid.Naveed Siddiqi, senior partner at Novo Holdings — which led the series C — previously described ASN51 as offering the "potential for a paradigm shift" in neurodegenerative disease treatment. For more on how new Alzheimer's drugs like Biogen and Eisai's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab) have been duking it out in the quest to reshape prescribing patterns, see – Physician Views Results: Kisunla comes out ahead of Leqembi in Alzheimer's race and Physician Views Results: Leqembi leaps ahead, thanks to new dosing regimen.Asceneuron has said that through OGA inhibition, ASN5 targets tau protein aggregation to slow down the progression of Alzheimer's disease. It has shown potential in preventing protein aggregation in other diseases such as Parkinson's disease and amyotrophic lateral sclerosis.The company is also developing another OGA inhibitor, called ASN90, as a potential treatment for progressive supranuclear palsy and other tau-related dementias. Ferrer acquired worldwide rights to ASN90 in 2023.