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.

项目概要/摘要 我们谓词 STTR 第一阶段拨款 (1R41CA261292-01) 的总体目标是开发一个实时 生物治疗产品（即，过度表达植物酶的生物工程细菌，以 保护性胶囊直接连接到结肠）用于将 SN-38 有效糖基化为 SN-38 葡萄糖 减轻癌症患者伊立替康引起的严重迟发性腹泻（SDOD）。 目前，尚无可成功控制剂量限制性肠道毒性的治疗方法 约 15% 接受标准伊立替康治疗的患者会出现伊立替康（3 级或 4 级腹泻）。 此外，如果没有有效管理伊立替康诱导的 SDOD 的解决方案，转移性 难治性癌症患者无法维持其所需的高剂量伊立替康治疗 癌症治疗。我们相信 DDB 将有助于更好地管理 SDOD，从而改善 由于腹泻的严重程度和发生率降低、发病率和死亡率降低，生活质量得到改善 停止化疗和住院费用。谓词第一阶段的具体目标 STTR 应用程序是为了 1) 开发可追溯、安全和活性的 DDB 以解毒 SN-38，2) 开发 经结肠优化的胶囊递送可追踪且高活性的冻干 DDB，以及 3) 评估 2 种活性 DDB 在伊立替康诱导的 SDOD 大鼠模型中的安全性和有效性。为了拿下这个 技术从实验室到市场的速度更快、成功，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、研发和业务运营融资战略、价值主张、产品 定价以及与大型制药公司的战略合作伙伴关系。然而，我们需要稳固的市场和客户 研究活生物治疗市场格局，以制定现实的前进道路。到 为了帮助我们朝这个方向努力，Sanarentero 组建了一个 3 人团队来参加 NIH 的 I-Corps 计划旨在为客户提供 SBIR/STTR 第一阶段获奖者的装备 发现研究。在本计划结束时，我们希望能够从以下方面收集足够的批判性知识： 进行客户和利益相关者访谈，这将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 DDB 的市场成功。