GS-9911

Gilead Sciences has axed half a dozen programmes from its portfolio, including candidates partnered with Novo Nordisk and Arcus Biosciences. The pipeline cull was disclosed in the company's second-quarter financial report on Thursday, when it also announced encouraging early uptake for its HIV prevention shot Yeztugo (lenacapavir) (see – Spotlight On: With Yeztugo's launch off to the races, Gilead ups HIV guidance).The pipeline prioritisation hit four cancer programmes, an experimental infectious disease asset, and Gilead's final metabolic dysfunction-associated steatohepatitis (MASH) hopeful. The drugmaker had been developing a triple-combination MASH treatment in collaboration with Novo Nordisk since at least 2020. The cocktail, comprising the Danish pharma's GLP-1 blockbuster semaglutide along with Gilead's experimental drugs cilofexor and firsocostat, was studied in the Phase II WAYFIND study.The discontinued candidates from Arcus also date back to a 2020 partnership pegged to last a decade. At the time, Gilead paid $175 million upfront and made a $200-million equity investment to co-develop and co-commercialise cancer immunotherapies from Arcus' pipeline — notably, the PD-1 inhibitor zimberelimab and several anti-TIGIT programmes, although the allure of TIGIT has since faded drastically following a number of high-profile setbacks within the class (see – Spotlight On: AstraZeneca leads TIGIT charge as another one bites the dust).In 2021, Gilead exercised options for several additional assets including etrumadenant, a dual adenosine A2a/A2b receptor antagonist, and the small-molecule CD73 inhibitor quemliclustat; both were pruned from the drugmaker's pipeline on Thursday.  The partners had been studying etrumadenant in combination with zimberelimab in the Phase II ARC-9 study for metastatic colorectal cancer, while quemliclustat was being evaluated in the Phase II ARC-8 trial in patients with metastatic pancreatic ductal adenocarcinoma, with or without the PD-1 inhibitor. Separate from the Arcus partnership, Gilead also cut two Phase I oncology programmes from its portfolio: MCL1 inhibitor GS-9716 and DGKα inhibitor GS-9911.The sixth asset to get the axe was the oral antiviral obeldesivir, specifically as a treatment for respiratory syncytial virus (RSV) in both children and adults. Gilead's decision to end development in RSV doesn't come as a surprise, as two trials were terminated in June due to "lower than expected" RSV infection incident rates. At the time, Gilead told FirstWord that a 400-person Phase II study of obeldesivir in Marburg virus disease was continuing as planned. The antiviral also failed the Phase III OAKTREE trial last year after it didn't improve time to symptom alleviation versus placebo in non-hospitalised COVID-19 patients without risk factors for severe disease.