Aligos与默克合作，希望扭转生物技术公司近期在NASH方面的疾

StephenW

With a potential $458M per target payday, Aligos teams up with Merck hoping to reverse biotech's recent NASH maladies
Max Gelman
Associate Editor

Just a few months after going public with a $150 million IPO, Aligos Therapeutics $ALGS is aiming to further capitalize on its momentum with a new NASH deal.

The biotech has teamed up with Merck to try to develop oligonucleotide therapies for the disease, a slate that could be worth up to $458 million in milestones per target. Aligos and Merck did not disclose how much would be paid upfront, but noted there would be another cash payment once the pair decides on a second target.

As part of the deal, Aligos will design and prepare the candidates for clinical studies, while Merck will take the lead on the R&D and commercialization efforts themselves. Aligos shares ticked up about 9% in early Monday trading.

It’s been a sharp rise for the San Francisco-based biotech since being founded in 2018. Aligos is focusing the vast majority of its efforts in liver diseases like hepatitis B and NASH, despite the latter field’s propensity for setbacks.

The company’s lead program, dubbed ALG-010133, is what Aligos calls a STOPS molecule, or an S-antigen transport-inhibiting oligonucleotide polymer. Having started a Phase I study in August for chronic hepatitis B, ALG-010133 aims to suppress the S-antigen in the hepatitis B virus itself.

Ultimately, Aligos says that can boost a patient’s compromised immune system and improve viral clearance in chronic hepatitis B. The company is expecting topline results for certain cohorts in the Phase I — measuring safety and antiviral activity in up to 12 weekly doses, both in healthy volunteers and virologically suppressed patients with CHB — sometime around the second half of 2021.

The past 24 months have brought nothing but difficulty for the NASH arena. Drug developers have been enticed by a potentially lucrative market, with some analysts projecting as much $20 billion in combined sales by 2025.

Gilead marked the first high-profile disappointments after its three-drug cocktail fizzled back in Dec. 2019, an effort that followed two other big defeats earlier in the year. None of the cocktail regimens induced a statistically significant increase in those trials’ primary endpoints.

Then this June, the FDA shot down Intercept’s own NASH program after several adcomm and hearing delays due to the Covid-19 pandemic and the agency wanting to see additional data. Regulators eventually rejected the drug because they were uncertain if the surrogate endpoint from their Phase III trial — reduction in liver fibrosis — would actually translate into benefit for patients.

In the subsequent months, both Genfit and Albireo shut down their NASH programs entirely. Though the former saw its stock price crushed by the flop, the latter emerged relatively unscathed given that its primary focus has been on other liver diseases like bile atresia and PFIC.

StephenW

Aligos每个目标发薪日的潜在收入为4.58亿美元，与默克合作，希望扭转生物技术公司近期在NASH方面的疾病
马克斯·盖尔曼
副主编

在以1.5亿美元的首次公开募股上市后仅几个月，Aligos Therapeutics $ ALGS的目标是通过一项新的NASH交易进一步利用其势头。

这家生物技术公司已与默克公司合作，尝试开发针对该疾病的寡核苷酸疗法，这一目标的目标价值可能高达4.58亿美元。 Aligos和Merck没有透露先付多少钱，但指出一旦双方决定第二个目标，便会有另一笔现金支付。

作为交易的一部分，Aligos将为临床研究设计和准备候选人，而默克将在研发和商业化工作中发挥领导作用。 Aligos股价在周一早盘交易中上涨约9％。

自从成立于2018年以来，这家总部位于旧金山的生物技术公司就出现了飞速增长。Aligos将其大部分工作都集中在了乙型肝炎和NASH等肝脏疾病上，尽管后者在这一领域容易遭受挫折。

该公司的主要计划被称为ALG-010133，被Aligos称为STOPS分子，即一种抑制S抗原转运的寡核苷酸聚合物。 ALG-010133已于8月开始对慢性乙型肝炎进行I期研究，旨在抑制乙型肝炎病毒本身中的S抗原。

最终，Aligos表示，它可以增强患者免疫系统受损的能力，并改善慢性乙型肝炎的病毒清除率。该公司期望第一阶段某些队列的主要结果-在健康状态下以每周12次的剂量测量安全性和抗病毒活性2021年下半年左右，志愿人员和接受病毒学抑制的CHB患者。

在过去的24个月中，给NASH带来了很多困难。药物开发商一直被潜在的利润丰厚的市场所吸引，一些分析师预计，到2025年，这些药物的总销售额将达到200亿美元。

吉利德（Gilead）在其三药鸡尾酒于2019年12月失败后标志着首次高调的失望，此举是在今年早些时候又发生两次重大失败之后。在这些试验的主要终点中，没有一种鸡尾酒疗法能引起统计学上的显着增加。

然后在今年6月，由于Covid-19大流行以及该机构希望查看更多数据，FDA在几次广告和听证会延误后，拒绝了Intercept自己的NASH计划。监管机构最终拒绝了该药物，因为他们不确定III期临床试验的替代终点（肝纤维化的减少）是否真的可以为患者带来利益。

在随后的几个月中，Genfit和Albireo都完全关闭了他们的NASH计划。尽管前者的股价受到了失败的打击，但后者的表现却毫发无损，因为它的主要重点是其他肝脏疾病，例如胆汁闭锁和PFIC。