In July 2016, we initiated a SER-262 Phase 1b dose-escalating study, the first clinical trial conducted using a rationally designed, fermented 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 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 SAEs 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 suggest that vancomycin pretreatment supports robust engraftment of our microbiome therapeutic candidates.
We are also designing SER-155, a rationally designed product candidate to prevent infections and improve GI barrier function (including the consequences of GvHD) in patients following allo-HSCT liver 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 reduced microbiome diversity are far more likely to die due to infection and/or lethal GvHD (Taur et al., Blood, 2014; Jenq et al, Biology of Blood and Marrow Transplantation, 2015). The selection of the patient population will be based on preclinical data, and the assessment of our clinical development plan, regulatory path and market opportunities. We plan to conduct studies in animal models as well as conduct further in vitro characterization of individual strains, in order to define and nominate a composition for clinical development In November 2017, we announced that we were awarded a grant from CARB-X (Combating Antibiotic-Resistant Bacteria Accelerator) 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 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 future steps in the development of both SER-262 and SER-155.
Sales and Marketing
If SER-109 is approved in the United States and Canada, we believe it can be commercialized with a focused specialty sales force of 100 or fewer sales representatives that will target gastrointestinal and infectious disease physicians, which are the two primary groups of physicians who treat multiply recurrent CDI patients.
In January 2016, we entered into an agreement with Nestec Ltd., or NHS, for the development and commercialization outside of the United States and Canada of our product candidates in development for CDI and IBD, including UC and Crohn’s disease. The agreement will support the development of our portfolio of products for CDI and IBD in markets outside of the United States and Canada and provide financial support for our ongoing research and development.
The production of live bacterial products is highly specialized. Owing to their hardiness and environmental persistence, production of spore-forming organisms poses unique considerations for product, personnel, and facility protection. Manufacturing activities with spores are subject to specialized regulations. We expect that a typical commercial fermentation will yield on the order of hundreds or thousands of doses per liter depending on the product and its composition. Additionally, because a given total dose is split between several strains, the per-strain requirements for production may be even lower. As a result, we believe the high productivity relative to the dose level will enable production scales for both clinical and commercial supply to be modest.