Preventing chemotherapy-related toxicities and infections with a novel phosphorylated triblock copolymer

PROJECT SUMMARY Covira Surgical, Inc. is developing a first-in-class agent for preventing chemotherapy-related gastrointestinal (GI) toxicities and lethal infections. Chemotherapy renders patients more susceptible to infection - many if most of which originate from the gastrointestinal track flora. Chemotherapy causes a major disruption in the gastrointestinal tract structure (i.e., mucosal ulceration, loss of tight junction permeability, submucosal edema, inflammatory cell infiltrations, etc.) and microbiome (i.e., dysbiosis). As a result, chemotherapy induced GI tract toxicity can lead to treatment disruptions, potential cancer progression, additional hospitalizations, and increased mortality. Compared to the general population, cancer patients have a mortality rate of fatal infections almost three times higher. Given these facts, infection is considered one of the most serious chemotherapy-related toxicities and many, if not most patients receive antibiotics during the course of their chemotherapy which can lead to further acquisition of antibiotics resistant strains of bacteria. Therefore, there is an urgent need for novel therapies to help reduce chemotherapy-related GI toxicities and infections that do not involve the addition of broader and more powerful antibiotics. Covira Surgical, Inc. intends to address this urgent need by developing a first-in-class agent capable of preserving the beneficial effects of the gut microbiome while suppressing its harmful effects. The gut microbiome plays a key role in modulating chemotherapy-related toxicity and efficacy, drug metabolism, and tumor microenvironment. Our agent – CS-0003 – is a novel, orally administered, non-antibiotic phosphate-rich mucoadhesive polyethylene glycol. CS-0003 can promote the retention and growth of the native microbiome while suppressing the proliferation and dissemination of lethal pathogens from the gut. CS-0003 provides microbes with a readily available source of phosphate while physically shielding bacteria away from the endothelial surface, thus behaving as a surrogate mucin that cannot be absorbed. This approach allows the gut microbiome to positively influence the immune system and GI tract. Our animal studies to date have demonstrated that CS-0003 is distributed along the entire GI tract and is safe and well-tolerated. Successful completion of this Phase I project will demonstrate that CS-0003 is safe and efficacious in ameliorating chemotherapy-induced toxicity and infection in mice treated with two common chemotherapeutic agents.