Development of Drug Detoxifying Bacteria for Chemotherapy Induced Gut Injury

开发用于化疗引起的肠道损伤的药物解毒细菌

• 批准号: 10560782
• 负责人: MING HU
• 金额: $ 5.5万
• 依托单位: SANARENTERO LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10560782
• 关键词: Administrative Supplement; Award; Bacteria; Biological Response Modifier Therapy; Biomedical Engineering; Businesses; Cancer Patient; Clinic; Clinical; Colon; Development; Diarrhea; Disseminated Malignant Neoplasm; Dose; Dose-Limiting; Enzymes; Freeze Drying; Glucose; Grant; Hospital Costs; Hospitalization; Incidence; Injury; Innovation Corps; Interview; Intestines; Learning; Life Expectancy; Modeling; Morbidity - disease rate; Patients; Pharmaceutical Preparations; Phase; Plants; Price; Process; Quality of life; Rattus; Recurrent disease; Refractory; Research; SN-38; Safety; Severities; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Solid; Techniques; Technology; Toxic effect; Treatment Cost; United States National Institutes of Health; cancer therapy; capsule; chemotherapy; commercialization; drug development; glycosylation; improved; irinotecan; member; mortality; novel therapeutics; operation; overexpression; prevent; programs; refractory cancer; research and development; side effect; success

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 R&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.

项目摘要/摘要 我们的谓词STTR第一阶段拨款(1R41CA261292-01)的总体目标是开发一种LIVE 生物治疗产品(即过量表达植物酶的生物工程菌) 用于SN-38到SN-38葡萄糖的有效糖基化的保护胶囊) 减轻伊立替康引起的癌症患者严重迟发性腹泻(SDOD)。 目前，还没有有效的治疗方法来成功地管理剂量限制的肠道毒性。 在接受标准伊立替康治疗的患者中，约有15%的患者出现伊立替康(3级或4级腹泻)。 此外，如果没有有效处理伊立替康引起的SDOD的解决方案，转移 难治性癌症患者无法维持高剂量的伊立替康治疗， 癌症治疗。我们相信，DDB将允许更好地管理SDOD，从而改善 由于腹泻的严重程度和发病率、发病率和死亡率降低而导致的生活质量 停止化疗，住院费用。谓词阶段I的具体目标 STTR的应用是：1)开发可溯源、安全、有效的滴滴涕解毒SN-38；2)开发 一种结肠优化的可追踪和高活性冻干DDB的胶囊释放，以及3)评价 2种活性DDBs在伊立替康诱导的SD大鼠模型中的安全性和有效性因为我拿了这个 技术从实验室更快地成功地推向市场，Sanarentero正在开发过程中 可行的商业模式和商业化战略，包括知识产权组合、临床和监管 战略、研发和业务运营的融资战略、价值主张、产品 定价，以及与大型制药公司的战略伙伴关系。然而，我们需要坚实的市场和客户 在活的生物热学市场格局中进行研究，以制定一条现实的前进道路。至 为了帮助我们朝着这个方向努力，Sanarentero组建了一个3人团队参加 NIH的I-Corps计划旨在为客户中的SBIR/STTR第一阶段获奖者提供装备 发现性研究。在本节目结束时，我们希望收集足够的批判性知识 与客户和利益相关者进行面谈，使我们能够重新调整/重新定义我们当前的 商业模式和商业化战略，以最大限度地提高我们的DDB的市场成功。