Seres Therapeutics Presents Data Across its Broad Microbiome Pipeline Including New 24-Week Data from SER-109 Phase 3 ECOSPOR III Study in Recurrent C. Difficile Infection at Digestive Disease Week 2021
– Data validates strength of Seres’ investigational microbiome therapeutics pipeline in potentially addressing unmet treatment needs in recurrent C. difficile infection and ulcerative colitis –
– In Phase 3 ECOSPOR III study, SER-109 significantly reduced recurrence rates of C. difficile infection at 24 weeks with an observed safety profile comparable to placebo –
– Preclinical data support the potential of SER-301 as a therapeutic modality for mild-to-moderate ulcerative colitis through microbiome restoration –
“This landmark study of SER-109, culminating in the full set of 24-week data, reinforces the potential of its first-in-class clinical profile. In the Phase 3 ECOSPOR III study, SER-109 was observed to rapidly restore the microbiome and significantly reduce the risk of recurrence over time for patients with recurrent C. difficile infection—all with a safety profile comparable to placebo,” said
On Sunday, Seres will also present SER-109 data comparing the modulation of primary and secondary bile acids (BAs) in ECOSPOR III study participants in an oral presentation. The shift in bile acids is believed to be an important mechanism by which SER-109 exerts its clinical benefits.
Additionally, Seres will present preclinical data from SER-287 and SER-301, investigational microbiome therapeutics that are being evaluated for the treatment of mild-to-moderate ulcerative colitis in poster and oral presentations at the meeting.
ECOSPOR-III Phase 3 Trial of SER-109 (Poster Fr572)
Final 24-week efficacy and safety results from the SER-109 ECOSPOR III Phase 3 study (ClinicalTrials.gov identifier: NCT03183128), a multicenter, randomized, placebo-controlled study that enrolled 182 patients with multiple rCDI, indicate that SER-109 was observed to maintain durable efficacy at 24 weeks following dosing, resulting in reducing the risk of rCDI compared with placebo. The safety profile observed to date has been comparable to placebo.
Significantly fewer patients administered SER-109 experienced rCDI compared to the placebo arm at Week 24 (21.3% vs. 47.3%, p-value <0.001), a relative risk reduction of 54%. SER-109 resulted in a 26% absolute reduction of recurrence of CDI compared to placebo at 24 weeks post-treatment. This is comparable to the 27% absolute reduction of recurrence observed in the trial at Week 8.
“As a clinician treating people living with recurrent C. difficile infection, I recognize the serious and often debilitating impact it has on their lives. The SER-109 Phase 3 data provide hope that an orally administered microbiome therapeutic, with an entirely new treatment modality, has the potential to alter the devastating cycle of recurrence that these people face,” said
In the Phase 3 study, SER-109 was observed to be well tolerated, with the overall incidence of adverse events at Week 24 comparable between the SER-109 and placebo arms. Treatment-emergent serious adverse events (SAEs) were observed in the active arm at a rate lower than in the placebo arm (n=15, 16.7%; n=19, 20.7%).
Previously reported topline data from ECOSPOR III indicated that the study achieved its primary endpoint at eight weeks post-treatment and a sustained clinical response rate of approximately 88% was observed. Seres is currently conducting an ongoing open-label study of SER-109 in patients with rCDI (ClinicalTrials.gov identifier: NCT03183141), with full enrollment anticipated in Q3 2021. Additional information can be found at serescdiffstudy.com.
CDI is one of the top three most urgent bacterial threats in the
In addition, in an oral presentation on
Ulcerative Colitis Preclinical Data
Seres will also present preclinical data for SER-301, a rationally-designed, cultivated microbiome therapeutic candidate for the treatment of ulcerative colitis (UC).
“Despite the availability of treatment options for patients with ulcerative colitis, there are still significant gaps—particularly for those living with mild-to-moderate disease who have limited options. When these few options fail, the recourse is mainly treatments that are used in moderate-to-severe disease, many of which have significant adverse events including immune suppression and risk of infections,” said
SER-301 is being evaluated in a Phase 1b study in adults with mild-to-moderate UC to evaluate safety and tolerability and to test the hypothesis that engraftment of drug product species modulates microbe-associated metabolites to reduce intestinal inflammation and improve epithelial barrier integrity.
Preclinical assessments of SER-301 used in vitro and in vivo models of colitis to evaluate the ability of SER-301 to promote immune homeostasis in the colon and to counterbalance inflammatory stimuli to prevent the development of colitis. In vivo animal model studies demonstrated that SER-301 is capable of reversing established intestinal inflammation and the development of colitis in an animal model. Further in vitro human cell-based assays confirm the bacteria in SER-301 can reduce induction of pro-inflammatory activity in intestinal epithelium cells and improve epithelial barrier integrity.
UC is a serious chronic condition affecting more than 700,000 patients in the
An oral presentation of SER-301 design and in vitro properties will be presented at DDW on
Posters and presentations will be available for 90 days on the DDW conference website.
SER-109 is an oral microbiome therapeutic candidate consisting of a consortium of highly purified Firmicutes spores, which normally live in the healthy microbiome. SER-109 is designed to prevent further recurrences of CDI in patients with a history of multiple infections by modulating the disrupted microbiome to a state that resists C. difficile colonization and growth. The SER-109 manufacturing purification process is designed to remove unwanted microbes thereby reducing the risk of pathogen transmission beyond donor screening alone. The
SER-287, an investigational oral microbiome therapeutic candidate consisting of a consortium of highly purified Firmicutes spores, is designed to normalize the gastrointestinal microbiome of individuals with UC. Preclinical colitis animal models and in vitro screens provide evidence that SER-287 administration has the potential to reduce pathology and modulate inflammatory and immunological functional pathways. SER-287 has been granted Fast Track Designation by the FDA for the induction and maintenance of clinical remission in adult subjects with active mild-to-moderate UC. SER-287 has been designated an Orphan Drug for pediatric UC by the FDA.
SER-301 is a consortium of cultivated bacteria designed using our reverse translational discovery platform that incorporates analysis of microbiome biomarkers from human clinical data and preclinical assessments using human cell-based assays and in vitro/ex vivo and in vivo disease models. SER-301 is designed to reduce induction of pro-inflammatory activity, improve epithelial barrier integrity and TNF-α driven inflammation in intestinal epithelial cells, or IECs, and modulate UC-relevant anti-inflammatory, innate and adaptive immune pathways. SER-301 is being produced using our advanced fermentation, formulation and delivery platforms. It includes strains delivered in spore form, as well as strains cultivated in non-spore (vegetative) form and delivered using enterically-protected technology designed to release in the colon.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including the potential of microbiome therapeutics to treat and prevent disease, the timing and results of our clinical studies, the potential approval of any of our products, the ultimate safety and efficacy data for our products, and other statements which are not historical fact.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; the impact of the COVID-19 pandemic; our unproven approach to therapeutic intervention; the lengthy, expensive and uncertain process of clinical drug development; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates and develop and commercialize our product candidates, if approved; and our ability to retain key personnel and to manage our growth. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the