Company continues to advance NLRP3 neuroinflammation program, with decision on future of obesity program expected in Q1 2025.
Longevity biotech BioAge Labs has announced the discontinuation of its STRIDES Phase 2 clinical trial, which evaluated its investigational drug azelaprag for the treatment of obesity. The decision follows observations of liver transaminitis in a subset of participants treated with the drug, though the cases were not accompanied by clinically significant symptoms. Following the news, BioAge, which announced its IPO earlier this year, saw its stock price fall around 75%.
Transaminitis refers to elevated levels of a group of enzymes essential for liver function, including detoxification and substance breakdown, and can signal underlying liver issues. To date, 204 subjects had been enrolled in the trial, which studied azelaprag alone and in combination with tirzepatide (marketed by Lilly as Zepbound). Transaminase elevations were observed in 11 participants in the azelaprag treatment groups. No such elevations were observed in participants receiving tirzepatide alone.
Azelaprag is an orally available small molecule agonist mimicking the activity of apelin, a regulatory peptide associated with exercise-induced benefits. It was thought that the drug’s mechanism would complement GLP-1s, targeting processes that help burn fat while preserving muscle function, and it had previously demonstrated potential in promoting metabolism and preventing muscle atrophy during periods of bed rest in a Phase 1b trial.
The emerging safety concerns prompted BioAge to halt dosing and enrollment in STRIDES. The company has notified investigators and regulatory authorities, including the FDA, and plans to conduct follow-up assessments for all enrolled participants off drug. A detailed analysis of the trial data is underway, with updated plans for azelaprag expected to be shared in the first quarter of 2025.
Dr Kristen Fortney, co-founder and CEO of BioAge Labs
In a statement, BioAge CEO Kristen Fortney stressed the company’s commitment to patient safety.
“We made the difficult decision to discontinue the STRIDES Phase 2 study of azelaprag because it became clear that the emerging safety profile of the current doses tested is not consistent with our goal of a best-in-class oral obesity therapy,” she said. “While this outcome is a significant disappointment, we remain encouraged by azelaprag’s promising preclinical and Ph1b efficacy profile.”
Beyond azelaprag, BioAge continues to advance its broader pipeline, which leverages insights from its discovery platform based on human longevity data to identify key pathways in metabolic aging and develop therapeutic candidates targeting age-related diseases. Among these is a novel brain-penetrant NLRP3 inhibitor designed to address neuroinflammation, a common driver of metabolic and neurodegenerative diseases. This program, which features a small molecule inhibitor with a high potency and unique binding site, is on track for an Investigational New Drug (IND) submission in the second half of 2025.
“We remain committed to our focus on developing therapies for metabolic aging,” added Fortney. “In parallel to assessing the next steps for the azelaprag program, we will continue to advance our NLRP3 inhibitor program as well as additional research programs with novel mechanisms emerging from our platform.”