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10-K
SERES THERAPEUTICS, INC. filed this Form 10-K on 03/06/2019
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We are also developing SER-401, for use with checkpoint inhibitors, or CPIs, in patients with solid tumors to enhance efficacy and improve survival. SER-401 is a microbiome therapeutic candidate sourced from healthy individuals who have been identified to have a microbiome signature that is similar to that observed in cancer patient responders to CPIs. CPIs block the mechanisms by which cancers evade detection and destruction by the immune system.  Observational studies of humans by a group led by our collaborator, Dr. Jennifer Wargo of MD Anderson Cancer Center, or MD Anderson, suggest that microbiome composition impacts response to CPIs. This has been supported by mouse model studies conducted by us and at MD Anderson that show that colonization with human responder microbes affected tumor response to CPI treatment, versus mice colonized with CPI non-responder microbes. These effects are thought to be a result of a specific microbiome signature enriched in certain members of the Firmicutes phylum of bacteria. We are working in collaboration with MD Anderson and the Parker Institute for Cancer Immunotherapy, or the Parker Institute, to evaluate the potential of SER-401, based upon this signature, and to modulate the immunological tone of subjects to improve response in patients with metastatic melanoma to CPI treatment. MD Anderson granted Seres an exclusive option, with pre-defined financial terms, to license intellectual property rights from them related to the use of bacteria in combination with CPIs. In collaboration with the Parker Institute and MD Anderson, we initiated a Phase 1b study of SER-401 in patients with metastatic melanoma.  Patients will be treated with either CPI alone, or in combination with SER-401, and observed for tumor regression and biomarkers of response to CPI. We expect to obtain Phase 1b study results in 2020.

On February 7, 2019, we announced corporate changes to focus our resources. We will now concentrate on completing the recently-initiated SER-287 Phase 2b study in mild-to-moderate UC, obtaining results from the ongoing SER-109 Phase 3 study for recurrent CDI and advancing the SER-401 Phase 1b study, in collaboration with the Parker Institute and MD Anderson, to evaluate augmenting CPI response in patients with metastatic melanoma. We will also continue to pursue focused preclinical activity on SER-301, a rationally-designed microbiome therapeutic candidate for UC, leveraging learnings obtained from our prior clinical study results.  In connection with the prioritization of these therapeutic candidates, we made changes to our management team and committed to a workforce reduction plan to reduce headcount by approximately 30 employees.  

Other Programs

 

In July 2016, we initiated a SER-262 Phase 1b dose-escalating study, the first clinical trial conducted using a rationally designed, fermented consortium of bacteria. SER-262 was rationally designed to be used following 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 using 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 were safety and tolerability and a comparison of the CDI recurrence rate in the SER-262 and placebo groups. Key secondary endpoints included 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. We believe the analyses of clinical data from both the SER-262 and SER-287 Phase 1b studies suggests that vancomycin pretreatment may augment engraftment of our microbiome therapeutic candidates.

 

We are also designing SER-155, a rationally designed, fermented microbiome therapeutic candidate designed to correct dysbiosis in patients following allogeneic hematopoietic stem cell transplants, or allo-HSCT, or solid organ transplants. This preclinical program is based on published clinical evidence from our collaborators at Memorial Sloan Kettering Cancer Center showing that allo-HSCT patients with dysbiosis are far more likely to die due to infection and/or lethal graft versus host disease, or GvHD. In November 2017, we were awarded a highly-competitive grant from Combating Antibiotic-Resistant Bacteria Accelerator, or CARB-X, to support continued preclinical research and early development work for SER-155. The CARB-X grant provides us with up to $2.5 million of research funding with potential for an additional $3.1 million for manufacture and investigational new drug application, or IND, upon completion of milestones.

 

We continue to evaluate microbiome pharmacokinetic and pharmacodynamic data from the SER-262 Phase 1b study, in addition to insights gained from research efforts with our other rationally designed Ecobiotic microbiome therapeutic candidates, in order to determine next steps in the development of both SER-262 and SER-155.

 

We have completed early stages of researching Ecobiotic microbiome therapeutics for the treatment of metabolic diseases, such as non-insulin dependent diabetes, non-alcoholic steatohepatitis, or NASH, and metabolic syndrome.  Research in these indications

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