Development of Drug Detoxifying Bacteria for Chemotherapy Induced Gut Injury

PROJECT SUMMARY/ ABSTRACT The overall objective of our predicate STTR Phase I grant (1R41CA261292-01) is to develop a live biotherapeutic product (i.e., a bioengineered bacteria overexpressing a plant enzyme delivered in a protective capsule directly to the colon) for the effective glycosylation of SN-38 to SN-38 glucose for alleviating irinotecan-induced severe delayed-onset diarrhea (SDOD) in the cancer patients. Currently, there is no therapy available to successfully manage the dose-limiting intestinal toxicity (Grade 3 or 4 diarrhea) of irinotecan in about 15% of the patients on standard irinotecan therapy. Moreover, without a solution for effective management of irinotecan-induced SDOD, metastatic refractory cancer patients are unable to maintain the high dose of irinotecan therapy required for their cancer treatment. We believe DDB will allow for better management of SDOD leading to improved quality of life due to reduced severity and incidences of diarrhea, morbidity and mortality due to cessation of chemotherapy, and hospitalization cost. Specific Aims of the predicate phase I STTR application are to 1) develop traceable, safe, and active DDB to detoxify SN-38, 2) develop a colon-optimized capsule delivery of traceable and highly active lyophilized DDBs, and 3) evaluate the safety and efficacy of 2 active DDBs in the irinotecan-induced SDOD rat model. For taking this technology from lab to market faster and successfully, Sanarentero is in the process of developing a viable business model and commercialization strategy including IP portfolio, clinical and regulatory strategies, financing strategies for Randamp;D and business operations, value proposition, product pricing, and strategic partnership with big Pharma. However, we need solid market and customer research in the live biotherpeautics market landscape for developing a realistic path forward. To aid in our efforts in this direction, Sanarentero has put together a 3-member team to participate in the I-Corps at NIH program aims at equipping the SBIR/STTR phase I awardees in the customer discovery research. At the end of this program, we hope to gather sufficient critical learning from conducting customer and stakeholders interviews that will allow us to realign/redefine our current business model and commercialization strategies for maximizing the market success of our DDB.PROJECT NARRATIVE The proposed administrative supplement to STTR phase I award (1R41CA261292-01) for participating in I-Corps at NIH program aims towards learning the customer discovery techniques to assist Sanarentero in the development of a business model and commercialization plan for the novel drug detoxifying bacteria (DDB) efficacious against irinotecan- induced intestinal toxicity. Successful clinical adaptation of DDB will allow for reduction in treatment cost due to severe diarrhea-related hospitalization and improvement in the quality of life of the cancer patients on irinotecan chemotherapy. Additionally, the availability of this product in clinics is expected to increase the overall life expectancy of metastatic cancer patients with refractory/recurrent diseases by allowing the continuation of chemotherapy by preventing the dose-limiting side effects.