Microbiome company Seres Therapeutics announced the discontinuation of its Phase Ib trial of SER-401, an orally delivered consortia of bacteria that was intended to boost the efficacy of checkpoint inhibitors in patients with metastatic melanoma.
Microbiome company Seres Therapeutics announced the discontinuation of its Phase Ib trial of SER-401, an orally delivered consortia of bacteria that was intended to boost the efficacy of checkpoint inhibitors in patients with metastatic melanoma.
The company said it was motivated both by the challenges of patient enrollment during the COVID-19 pandemic and the progress of other candidates in its preclinical pipeline.
Safety data from 10 melanoma patients receiving checkpoint inhibitor Opdivo (nivolumab) showed SER-401 was well tolerated, compared with placebo. But poor enrollment pushed the company to end the trial, said Kristin Ficks Ainsworth, a Seres spokesperson. No patients had been enrolled in an arm designed to compare the therapy with fecal microbial transplant (FMT).
Two recent papers published in Science by researchers from Tel Aviv University and University of Pittsburgh/National Cancer Institute showed FMTs were well tolerated in patients and could improve the response to Opdivo and Keytruda (pembrolizumab), respectively, in some patients with metastatic melanoma.
Based on findings like these, the company continues to believe modulating the gut microbiome can improve clinical response to checkpoint inhibitors.
The company has not disclosed any additional programs for checkpoint-refractory therapies, but is in preclinical testing of another bacterial consortium, SER-155, with Memorial Sloan Kettering Cancer Center for antibiotic resistant bacterial infections, bacteremia and graft-versus-host disease in cancer patients received hematopoietic stem cell transplants, Ficks Ainsworth said.
“Oncology remains an area of substantial interest for Seres and we have an active R&D program evaluating various approaches and disease targets,” she said.
The company also plans to continue to work with its clinical partners, the Parker Institute for Cancer Immunotherapy (PICI) and The University of Texas MD Anderson Cancer Center.
The move by Seres echoes a December announcement from Evelo Biosciences, a competitor in the microbiome cancer space. Evelo is winding down its Phase I/II of ESP1503, an orally delivered strain of Bifidobacterium animalis lactis, despite positive safety data in an interim analysis of 15 patients with metastatic breast cancer taking Keytruda. Instead, Evelo is promoting preclinical candidate EDP1908, extracellular vesicles derived from gut bacteria that had better preclinical efficacy data.
At least five other companies have microbiome therapies in early clinical testing with checkpoint inhibitors, including 4D Pharma, Enterome, Genome & Company, Synlogic, and Vedanta Biosciences.
Seres is planning to file a Biologics License Application upon completion of a Phase III trial for its lead program SER-109, a consortium of bacterial spores for treating recurrent Clostridioides difficile infection. The company announced positive topline data last year. Seres also has two bacterial consortia in Phase II and Phase I testing, respectively, for ulcerative colitis.
