OGA

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。 据瑞士联邦临床试验数据库显示，瑞士一家小型生物技术公司Asceneuron 终止了一种用于治疗阿尔茨海默病的新型口服药物ASN51的中期试验。 Asceneuron首席执行官Barbara Angehrn Pavik拒绝提供终止试验的原因。根据登记表来看，公司表示是“战略决定”。 2024年7月，Asceneuron公布了一项1亿美元的C轮融资，以推进其O-GlcNAcase （OGA）抑制剂ASN51进入2期研究。根据该试验在数据库中的记录，该试验预计需要两年时间，但不到一个月就终止了试验。 C轮融资的资金预计将全额资助这项现已终止的试验。Asceneuron董事会成员Naveed Siddiqi表示这笔资金还可以将ASN51用于帕金森病和肌萎缩性侧索硬化症等其他适应症。 其实这不是第一款终止的阿尔兹海默症药物。 在这次筹资后不久，其主要竞争对手礼来表示，同一类别的一种药物未能通过第二阶段实验。就在今年2月，Biogen也放弃了同类型的一种早期药物。 这三家公司都在尝试开发OGA抑制剂，他们认为这种抑制剂可以减缓或抑制阿尔茨海默病患者体内tau蛋白的积聚。如果tau蛋白积累过多，这种蛋白质会损害神经元并产生神经退行性影响。 参考资料： www.endpts.com

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.