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10-Q
SERES THERAPEUTICS, INC. filed this Form 10-Q on 11/08/2018
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On October 2, 2017, we announced positive topline results from our Phase 1b clinical trial of SER-287 in patients with UC. The SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study enrolled 58 patients at 20 sites across the United States with active mild-to-moderate UC, with Total Modified Mayo scores of 4 to 10. Study subjects exhibited pre-study disease activity despite use of current therapies in a majority of subjects, which included 5-amino-salacylic acid, low dose corticosteroids, or immunomodulatory therapy.  Evaluation of SER-287 safety and tolerability was a primary study endpoint and study results demonstrated no drug-related serious adverse events and no imbalance in adverse events in SER-287-treated patients as compared to patients treated with placebo.

Analyses of study patients’ microbiome data, a co-primary study endpoint of the trial, demonstrated that SER-287 induced dose-dependent engraftment of SER-287-derived bacterial species into the colonic microbiome of the patients treated with SER-287. Patients administered vancomycin pre-treatment followed by daily administration of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort corresponded with the study arm where the most significant clinical benefits were observed, including clinical remission and endoscopic improvement. Differences in the composition of the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable throughout the dosing period of the trial and were also observed at four weeks post administration of the final SER-287 dose. The SER-287 Phase 1b study microbiome data support the previously reported clinical results. The Company has made operational progress working to initiate a planned SER-287 Phase 2b clinical study. To expedite the time and resources required to obtain top-line results from this study, we have modified the prior planned four arm placebo-controlled study design into a smaller, three arm study in approximately 200 patients that will include two different doses of SER-287, both following pretreatment with oral vancomycin, and a placebo arm. We have designed this study as a potentially pivotal trial, and we are awaiting feedback from the FDA on this final study design.

We are currently in the final stages of initiating a Phase 1b clinical study with our collaborators at MD Anderson Cancer Center, or MDACC, and the Parker Institute for Cancer Immunotherapy, or PICI, of SER-401, a biologically sourced microbiome therapy designed to replicate the bacterial signature found in the approximately one third of patients who have a robust response to anti-PD-1 therapy.   SER-401 is designed to modify the cancer immune set point and meaningfully improve patients’ response to checkpoint inhibitor therapy.  The scientific basis for SER-401 is supported by published findings from our collaborator, Dr. Jennifer Wargo of MDACC, indicating that a specific set of bacteria in the gastrointestinal microbiome can have an important role in determining the immunological response to checkpoint inhibitor therapy. Our own preclinical research has extended these findings and continues to ascertain how specific bacterial species impact the response to checkpoint inhibitors.  These data demonstrate the strong role of specific bacterial species in anti-tumor response to anti-PD-1 therapy and on the impact of the microbiome the immune system and on specific T cell classes, including CD8 and T regulatory cells.  

In July 2016, we initiated a SER-262 Phase 1b dose-escalating study, the first clinical trial conducted using a rationally designed ecology of bacteria. SER-262 was designed to be used following CDI antibiotic treatment to prevent an initial recurrence of CDI. We have established various capabilities to enable the development of rationally designed microbiome therapeutics including metagenomic and metabolomic profiling, use of curated reference computational databases and proprietary in silico algorithms for drug design, an extensive proprietary bacterial library, advanced manufacturing processes, and capabilities to conduct pharmacokinetics and pharmacodynamics analyses in clinical studies. SER-262 contains a consortium of 12 bacterial strains derived from a manufacturing process that utilizes in vitro fermentation and does not require human donor material.

The Phase 1b clinical study was a 24-week, randomized, placebo-controlled, dose-escalation trial. The primary endpoints of the study are safety and tolerability and a comparison of the CDI recurrence rate in the SER-262 and placebo groups. Key secondary endpoints include analysis of SER-262 bacterial strain engraftment. Top line clinical and microbiome results from the study are available. No drug-related serious adverse events were observed. No significant differences were observed in the recurrence rates in patients administered SER-262 as compared to placebo, however, we observed a statistically significant reduction in CDI recurrence rates in patients pretreated with vancomycin followed by SER-262, as compared to those treated with metronidazole followed by SER-262. This observation corresponded with an increase in SER-262 microbiome engraftment in patients pretreated with vancomycin. Clinical data from both the SER-262 and SER-287 studies indicate that vancomycin pretreatment supports robust engraftment of our microbiome therapeutic candidates.

Our expenses may increase substantially in connection with our ongoing and planned activities, particularly as we:

 

continue the clinical development of SER-109, our lead product candidate, in the Phase 3 clinical study;

 

continue the clinical development of SER-287 for the treatment of UC and potential other studies of IBD;

 

initiate the clinical development of SER-401, a microbiome therapeutic candidate for use with CPIs in a Phase 1b clinical trial in patients with metastatic melanoma;

 

continue the clinical development of SER-262 to be used following antibiotic treatment of primary CDI to prevent an initial recurrence of CDI;

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