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.

这项小型企业创新研究（SBIR）II期项目的更广泛/商业影响着重于人类肠道微生物组，这是居住在胃肠道中的微生物的复杂而动态的微生物社区。 肠道微生物组会影响各种人类疾病，例如2型糖尿病和炎症性肠病。总的来说，这些疾病每年在美国遭受了超过1.2亿人的患者治疗的损失超过5800亿美元。这些疾病中许多治疗的当前标准护理具有可变的功效和严重的副作用。使用微生物组疗法（即包括活细菌）作为一种难以治疗疾病的新一代药物来调节肠道微生物组的兴趣越来越大。但是，该行业目前缺乏可靠的方法和成本效率开发有效的微生物组治疗剂的方法。具体而言，微生物组治疗发展的最大障碍是缺乏将早期研究转化为药物发现和开发的预测性临床前模型。拟议的项目旨在通过开发首个综合，计算，药物设计和发现平台来解决使用微生物组治疗剂的障碍。当前，微生物组治疗剂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确定目标治疗候选物的潜在微生物菌株。结果，这种方法需要广泛的体外和体内实验，这大大增加了开发计划的长度和成本。这些挑战导致了一种效率低下且不可预测的微生物组治疗开发过程，从而限制了可以在全球范围内挽救数百万人生的有效微生物疗法的数量。该项目通过可靠和成本效益地确定各种适应症的治疗候选者来应对这些挑战。该平台可以取代药物发现阶段中当前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2型糖尿病的新治疗候选者，并在临床前研究中验证这些候选人的功效。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。