remission rates among the three treatment arms (10.3% for the full induction dose, n=68 and 10.6% for the step-down induction dose, n=66 versus 11.6% for placebo, n=69). There were also no meaningful differences observed across the three treatment groups for endoscopic improvement, endoscopic remission or symptomatic remission.
“While the efficacy results in this trial did not meet the pre-defined threshold, we believe this data-rich study, including microbiome analyses expected in the second half of 2021, will provide valuable insights to inform continued development of our pipeline, including SER-301, our next generation investigational candidate for UC,” said Lisa von Moltke, M.D., Chief Medical Officer at Seres. “We are grateful for everyone who made this study possible, including the study investigators, and in particular, the patients and their families.”
Treatment emergent adverse events (AEs) were observed in 67.6%, 46.2% and 50.7% of subjects in the induction dose, step-down dose (both of which included six days of oral vancomycin preconditioning) and placebo treatment arms, respectively. The majority of observed AEs were mild or moderate in intensity. The most commonly observed AEs were worsening of UC, diarrhea, nausea and abdominal distension. Four participants on active treatment reported serious treatment emergent adverse events (worsening ulcerative colitis, colonic dysplasia, congestive heart failure with decreased hemoglobin, and appendicitis), as did one on placebo (worsening ulcerative colitis).
The Company continues to advance its SER-301 program currently in a Phase 1b study that is testing the hypothesis that engraftment of drug product species modulates microbe-associated metabolites to reduce intestinal inflammation and improve epithelial barrier integrity in adults with mild-to-moderate UC. The Phase 1b is currently enrolling in Australia and New Zealand.
SER-287 and SER-301 are both consortia of bacteria found in the gastrointestinal tract of healthy individuals. However, important compositional and potential therapeutic differences exist between the investigational drugs. SER-287 is a donor-derived product candidate, whereas SER-301 utilizes Seres’ next generation technology and is based on rationally designed, cultivated consortia of bacteria. The design of SER-301 has leveraged the Company’s reverse translation platforms and capabilities that can evaluate at high resolution how microbes in the gastrointestinal tract are interacting with one another and human cells and tissues to impact disease pathways. The bacteria in SER-301 are targeted at, and specifically selected in, an effort to optimize the reduction of pro-inflammatory activity, improve epithelial barrier integrity and TNF-a driven inflammation in intestinal epithelial cells, and modulate UC-relevant anti-inflammatory, innate and adaptive immune pathways.
Results from the SER-287 ECO-RESET study, including additional efficacy and safety results as well as microbiome analyses, will be submitted for presentation at a future scientific meeting.
As of June 30, 2021, Seres had approximately $229 million in cash, cash equivalents and marketable securities. The June 30, 2021 cash balance does not include the upfront fee of $175 million that has been received by Seres following the SER-109 Co-Commercialization License Agreement announced on July 1, 2021 with Nestlé Health Science.
