SBIR Phase II: An omics-based computational drug design and discovery platform for next generation microbiome therapeutics

SBIR II 期：基于组学的计算药物设计和发现平台，用于下一代微生物组疗法

• 批准号: 2228069
• 负责人: Mohammad Soheilypour
• 金额: $ 100万
• 依托单位: NEXILICO, INC.
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2228069&HistoricalAwards=false
• 关键词: SBIR; Phase; II; omics; based

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project focuses on the human gut microbiome, the complex and dynamic community of microorganisms residing in the gastrointestinal tract. The gut microbiome influences a variety of human diseases, such as Type 2 Diabetes and inflammatory bowel disease. Collectively, these diseases afflict more than 120 million people and cost more than $580 billion in patient treatments in the US annually. The current standard care of treatments for many of these diseases have variable efficacy and serious side effects. There is increasing interest in modulating the gut microbiome using microbiome therapeutics, i.e., therapeutics comprising living bacteria, as a new generation of drugs for difficult-to-treat diseases. However, the industry currently lacks a reliable approach to systematically and cost-effectively developing effective microbiome therapeutics. Specifically, the largest barrier to microbiome therapeutic development is the lack of predictive preclinical models to translate early-stage research into drug discovery and development.The proposed project seeks to address the barrier to the use of microbiome therapeutics by developing a first-of-its-kind computational platform, as the first comprehensive, computational, drug design and discovery platform. Currently, the development of microbiome therapeutics is based on a series of experimental and statistical steps that identify the potential microbial strains for target therapeutic candidates in an empirical and iterative process. As a result, this approach requires extensive iterative in vitro and in vivo experiments, which substantially increase the length and cost of the development programs. These challenges have resulted in an inefficient and unpredictable microbiome therapeutic development process, limiting the number of efficacious microbiome therapeutics that could save millions of lives worldwide. This project addresses these challenges by reliably and cost-effectively identifying therapeutic candidates for a wide range of indications. This platform could replace the current iterative and unpredictable development process in the drug discovery stage. The utility of the platform will be demonstrated by developing new therapeutic candidates for Type 2 Diabetes and validating the efficacy of these candidates in preclinical studies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业创新研究（SBIR）第二阶段项目的更广泛/商业影响集中在人类肠道微生物组，即居住在胃肠道中的复杂和动态的微生物群落。 肠道微生物组影响多种人类疾病，如2型糖尿病和炎症性肠病。总的来说，这些疾病困扰着超过1.2亿人，每年在美国的患者治疗费用超过5800亿美元。目前对许多这些疾病的标准治疗具有不同的疗效和严重的副作用。人们越来越关注使用微生物组治疗剂来调节肠道微生物组，即，包含活细菌的治疗剂，作为新一代难治性疾病的药物。然而，该行业目前缺乏一种可靠的方法来系统地、经济有效地开发有效的微生物组疗法。微生物组疗法开发的最大障碍是缺乏预测性临床前模型，无法将早期研究转化为药物发现和开发。拟议的项目旨在通过开发首个同类计算平台来解决微生物组疗法使用的障碍，作为第一个全面的计算药物设计和发现平台。目前，微生物组疗法的开发基于一系列实验和统计步骤，这些步骤在经验和迭代过程中鉴定用于靶向治疗候选物的潜在微生物菌株。因此，这种方法需要大量的迭代体外和体内实验，这大大增加了开发计划的长度和成本。这些挑战导致微生物组治疗开发过程效率低下且不可预测，限制了可以挽救全球数百万人生命的有效微生物组治疗方法的数量。该项目通过可靠和具有成本效益地确定广泛适应症的治疗候选人来应对这些挑战。该平台可以取代目前药物发现阶段的迭代和不可预测的开发过程。该平台的实用性将通过开发新的2型糖尿病治疗候选药物和验证这些候选药物在临床前研究中的疗效来证明。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。