Donors are required to be in good health, and to possess a medical history that minimizes the risk of exposure to and transmission of an infectious disease. Donors are tested for infectious agents and screened for gastrointestinal and other health factors. After initial qualification, the donor is eligible to donate for a defined period of time. Donors are monitored for health status changes during the donation period. At the end of the donation period, the qualification assessment is repeated to help ensure the donor has maintained their health status. After successful completion of an exit screening, donations are released for use in manufacturing.
We initially process the donor material in our Cambridge manufacturing facility, and then transfer the process intermediate to a contract manufacturing organization, or CMO, to isolate and concentrate SER-109 for finishing to the oral capsule dosage form. The purified drug substance is tested for identity, potency and purity, and subsequently formulated into drug product where it is again tested for identity, potency, purity, and pharmaceutical properties in our Cambridge facility. The final drug product dosage form is four hard capsules for oral administration. Steps are specifically built into the process to remove and kill non-spore microbes. We have conducted validation studies demonstrating the ability of the process to inactivate and clear hypothetical extraneous pathogens of concern, and we believe we have sufficient data from these studies to support ongoing and proposed clinical trials.
Raw materials, intermediates, drug substance and drug product are tested using cGMP assays developed with our know-how to assess the key quality attributes of identity, potency and purity of the product. Identity testing has been developed to assure the presence of specific live spore forms in the product. Potency assays assure the intended dose of spores, and assess stability of the spores during storage. Stability of the dosage form is also confirmed. Proprietary microbiological purity assays have been developed to enable testing for microbial contaminants in the presence of the live spore product.
We believe we can address market demand with a relatively small-scale manufacturing process. If approved, we anticipate that we will be able to produce a sufficient commercial supply of SER-109 to meet estimated demand in the United States using donations from a modest number of donors.
We are developing SER-262, which is a synthetic fermented, multi-strain Ecobiotic microbiome therapeutic intended to be used following antibiotic treatment of primary CDI to prevent an initial recurrence of CDI. We have designed SER-262 to increase and improve diversity in the colonic microbiome after antibiotics treatment of primary CDI. The results of our Phase 1b/2 clinical study of SER-109 provided multiple insights in designing the spore ecology used in SER-262, which consists of a subset of bacteria found in SER-109. Pre-clinical studies of SER-262 have demonstrated efficacy in mouse models of CDI similar to those observed in pre-clinical studies of SER-109.
As part of our selection of SER-262 we screened multiple candidates for efficacy in animal models using SER-109 as a reference compound. SER-262 provided significant protection against CDI with reduced mortality, minimum weight loss and clinical score measures of efficacy. Strains in SER-262 have met initial bioprocess specifications for spore titer and yield, and each organism has been characterized by whole genome sequencing and a battery of in vitro tests and characterizations.
The result of testing in a pre-clinical mouse model of CDI are depicted in the diagrams below.