SBIR Phase I: AI-driven PROTAC drug discovery - Pioneering non-hormonal therapeutic targets for uterine fibroids and endometriosis

Opal Therapeutics Inc, San Francisco CA

Investigators

Abstract

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project lies in potentially developing new therapeutic options for women suffering from chronic gynecological conditions such as uterine fibroids and endometriosis. These conditions affect millions of women, causing chronic pelvic pain, painful menstruation, and infertility. Traditional drug discovery often overlooks female biology, leading to a lack of effective treatments and often necessitating surgical interventions. This project aims to develop a uterus-in-a-dish platform technology that rapidly identifies relevant disease mechanisms and possible new therapeutics specifically for fibroids and endometriosis. By focusing exclusively on female biology, this project seeks to discover innovative therapeutic solutions that significantly improve the quality of life for women, alleviating the physical, financial, and emotional burdens associated with these debilitating conditions. This Small Business Innovation Research (SBIR) Phase I project aims to develop an advanced screening platform that utilizes patient-derived uterine organoids to accurately capture disease pathology and identify therapeutic proteolysis-targeting chimeras (PROTAC) degraders for treating uterine fibroids and endometriosis. Despite the high prevalence and significant disability caused by these gynecological conditions, there has been a notable lack of non surgical therapeutic options from the pharmaceutical industry. In the past 15 years, only one drug has been developed for endometriosis-associated pain, and no new drugs have been developed for fibroids. To address this unmet need and create new therapeutic modalities for women’s reproductive health, the project goals include building a comprehensive gynecological biobank of patient samples, training AI algorithms to identify disease-relevant phenotypes in cell and organoid models from high-content images, employing in silico predictive molecular modeling to propose PROTAC structures to target disease phenotypes, and high-throughput screening of curated chemical libraries on organoid assays. Achieving these research objectives will yield new PROTAC structures with the potential to treat fibroids and endometriosis in patients. 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.