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SERES THERAPEUTICS, INC. filed this Form 10-Q on 05/09/2018
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In July 2016, we initiated a Phase 1b dose-escalating study for SER-262, the first clinical, rationally designed ecology of spore forming bacteria designed to be used following antibiotic treatment for primary CDI to prevent an initial recurrence of CDI. Based on our metagenomics expertise, proprietary in silico algorithms, extensive proprietary bacterial library, and advanced manufacturing capabilities, we believe we can rationally design microbiome therapeutic candidates for specific target indications, which we believe will have several advantages, including scaling up manufacturing to meet global demand in a reliable and reproducible manner and a competitive advantage in developing microbiome therapeutics. SER-262, available in oral capsule form, is derived from a manufacturing process that does not require human donor material. SER-262 contains a consortium of 12 bacterial strains in spore form constructed from strains from our microbiome strain library via in vitro fermentation.

The Phase 1b clinical study is a 24-week, randomized, placebo-controlled, dose-escalation trial. The present study was initially designed to evaluate a single dose administration of SER-262 at ascending spore doses ranging from 1x104 to 1x108 Spore Colony Forming Units, or SCFU, with each dosing cohort comprised of 10 subjects treated with SER-262 and two subjects administered placebo. Following analysis of prior SER-109 clinical studies that suggest higher doses of microbiome therapeutics may be important to rapidly address dysbiosis and provide increased efficacy, in mid-2017 we added additional multiple-dose cohorts to the Phase 1b study of 1x106, 1x107 and 1x108 SCFU per day of SER-262, for a three-day period.

The primary endpoints of the study are to evaluate the safety and tolerability of SER-262 and to compare the CDI recurrence rate between the SER-262 and placebo groups at up to eight weeks post-dosing. A secondary endpoint is the analysis of the SER-262 bacterial strain engraftment in patient microbiomes. As of now, we have received unblinded clinical data on all but the final 1x108 multiple dose cohort, which continues to enroll subjects.  No drug-related serious adverse events were observed in these first seven cohorts.  No relevant differences were observed in the relative risk of recurrence rates in patients administered SER-262 as compared to placebo. However, this small, first-in-human, Phase 1b study was not powered to detect a statistically significant difference in recurrence rates compared to placebo. A small group of placebo patients were included in this study and, in that group, no recurrences were observed in the seven cohorts analyzed clinically. In addition, there was a measurable difference in recurrence rates in patients treated with Vancomycin and SER-262, as compared to those treated with Metronidazole and SER-262 (4% versus 31%, respectively).  This difference was statistically significant with a p-value of 0.0049.  The medical literature suggests a recurrence rate of about 25% in patients treated solely with vancomycin for primary CDI.

Microbiome analysis has been conducted on the first five, lowest dose cohorts to assess drug pharmacokinetics.  We detected a majority of SER-262 strains in patients receiving SER-262; detection of strains was variable across subjects. Partial engraftment of strains was also a characteristic in our SER-109 clinical studies, and has been reported in fecal microbiota treatment of CDI.  Engraftment of SER-262 strains was associated with broader changes in the microbiome composition.  Microbiome profile differences, based on the antibiotics that were used to treat each patient’s CDI, were also demonstrated. Vancomycin led to more rapid and more robust engraftment of SER-262 strains as compared to Metronidazole.  More detailed microbiome and metabolomic analyses remain ongoing. These SER-262 proprietary data, the first ever obtained from a rationally-designed microbiome development candidate, will be used to inform the further development of SER-262 and our other 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;


advance the pre-clinical development of SER-401, a microbiome therapeutic candidate for use with checkpoint inhibitors (CPIs) in patients with solid tumors;


continue the clinical development of SER-262 to be used following antibiotic treatment of primary CDI to reduce recurrence after the initial episode of CDI;


conduct research and continue pre-clinical development of additional microbiome therapeutic candidates, including SER-155 and SER-301, our rationally designed IBD product candidate;


make strategic investments in manufacturing capabilities;


maintain and augment our intellectual property portfolio and opportunistically acquire complementary intellectual property;


potentially establish a sales and distribution infrastructure and scale-up manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;


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