Novel, Non-hormonal Therapeutic for Endometriosis

PROJECT SUMMARY: The ultimate goal of the project is to develop the first disease-modifying (‘curative’) and non-hormonal therapeutic for endometriosis. Endometriosis is considered one of the greatest overlooked epidemics in women’s health, affecting approximately 10% of women worldwide. It is a major cause of infertility and disability among individuals across all ethnicities. Shockingly, to date, there is no cure for this prevalent disease. The average time to diagnosis endometriosis is an abysmal 4-12 years. Currently, clinical management of endometriosis through hormonal treatment, pain therapies, or surgical interventions—which fail to reverse the disease or address the root cause—is often insufficient. Hormone pills and GnRH antagonists (which induce “medical menopause”) cause undesirable side effects, resulting in low patient compliance. Women who undergo endometriosis excision have a high likelihood of recurrence within 5 years of surgery, and many individuals who do not experience relief often resort to hysterectomies. This project is recognized as a high priority goal by NICHD, an NIH-wide aspirational goal, and an initiative aligned with the White House Initiative on Women’s Health. Our team has developed ENDO-205 as a novel therapeutic option for endometriosis by targeting a downstream component of a pathway known to contribute to endometriosis pathogenesis, migration, and invasion. Critically, ENDO-205 is only absorbed in endometriosis tissue and selectively inhibits a major, non- hormonal root cause of pathogenicity, leading to lesion regression and disappearance without altering estrous cyclicity. We have successfully accomplished milestones from our previous Phase I/II/IIB SBIR Grants which generated data that supports potent therapeutic efficacy with no toxicities. Further, our team has developed a formulation suitable for human use. In this CRP application, we will continue to advance the development and commercialization of ENDO-205 to support all activities necessary to commence Phase 1 clinical trials. We will manufacture GMP clinical drug substance and product, and place them on stability according to FDA ICH guidelines. We will also complete GLP genotoxicity and clinical pharmacology assessments necessary for IND submission. Lastly, we will ensure that key biochemical evaluations for Phase 1 human trials are properly validated. Due to the high unmet need for endometriosis therapeutics, successful completion of these aims will enable us to submit our application to the FDA for IND allowance and commence clinical trials. Ultimately, the successful completion of this project will offer women suffering from endometriosis a tolerable, non-hormonal solution to eliminate the disease.