Seres Therapeutics has formed a collaboration to test microbiome therapy SER-401 in combination with an anti-PD-1 checkpoint inhibitor. The Parker Institute for Cancer Immunotherapy is sponsoring the trial, which will take place at the MD Anderson Cancer Center.
In the randomized, placebo-controlled clinical trial, investigators at MD Anderson will assess the effect of giving SER-401 to patients with advanced metastatic melanoma who are being treated with an anti-PD-1 checkpoint inhibitor. SER-401 is a preclinical, orally-administered cocktail of live bacteria.
The planned trial will join a sea of studies assessing drugs designed to increase the proportion of patients who respond to checkpoint inhibitors. At this stage in development, the odds of SER-401 succeeding are long. But the potential rewards for Seres of moving beyond infectious diseases—an area where it has struggled in the clinic—and inflammatory conditions into cancer are significant.
“If this novel approach is successful at altering the microbiome and more importantly, also leads to better cancer patient responses to immunotherapy, this would mark an important milestone for the entire field,” Fred Ramsdell, Ph.D., VP of research at the Parker Institute, said in a statement.
News of the collaboration comes two weeks after MD Anderson researchers published a paper on how the gut microbiome modulates melanoma patients’ responses to anti-PD-1 drugs. The study identified significant differences between the diversity and composition of the gut microbiomes of responders and nonresponders to an anti-PD-1 immunotherapy. Researchers enrolled 112 melanoma patients in the study,
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The researchers then transplanted feces from responders and nonresponders into germ-free mice to assess whether the microbiome is a causal factor in treatment response. Anti-PD-1 therapies worked better in mice that received transplants from responders than those that received feces from nonresponders, suggesting that the microbiome influences treatment response.
“We propose that patients with a 'favorable' gut microbiome have enhanced systemic and anti-tumor immune responses mediated by increased antigen presentation, and improved effector T cell function in the periphery and the tumor microenvironment,” the authors wrote.
“In contrast, patients with an 'unfavorable' gut microbiome have impaired systemic and anti-tumor immune responses mediated by limited intratumoral lymphoid and myeloid infiltration and weakened antigen presentation capacity.”
The researchers characterized a “favorable” microbiome as having high diversity and abundance of bacteria from the Ruminococcaceae family, specifically Faecalibacterium. The gut microbiome was classed as “unfavorable” if it had low diversity and a high relative abundance of Bacteroidales.
Seres is yet to disclose details of the composition of SER-401. The deal to advance the candidate into the clinic is Seres’ second foray into oncology. The first came last year when Seres teamed up with Memorial Sloan Kettering Cancer Center to explore the use of microbiome therapeutics to improve outcomes in patients undergoing hematopoietic stem cell transplantation and to dial up the efficacy of checkpoint inhibitors.
The latest agreement gives Seres the exclusive option to license relevant intellectual property from MD Anderson.