R44HD100190

PROJECT SUMMARY Infertility is a global health problem. In the US alone, ~1.7 million women are treated for infertility every year. To improve infertility treatment, there is a strong need to promote patient-friendly methods for progesterone supplementation in assisted reproductive technology (ART). Intravaginal rings, which are well tolerated by women, are efficacious for contraception and hormone replacement therapy, and have high patient compliance, are now in development for ART. However, developing effective IVRs to deliver progesterone beyond 7 days is challenging due to limitations of current engineering processes, and difficulty in controlling release rates, thus mandating drug-specific customized IVR designs. Our goal is to address these limitations by revolutionizing the engineering and manufacturing processes for intravaginal rings, using a state-of-the-art 3D printing process known as continuous liquid interface production (CLIP™). Using the automated CLIP process, we can engineer and manufacture IVRs with surface geometries not achievable with traditional injection molding or extrusion, which help control drug release. CLIP enables us to precisely fine-tune diffusion and release of drugs, to achieve near complete release, and independently control IVR mechanical properties. Importantly, using CLIP, we can manufacture IVRs that provide sustained release of progesterone to cover the entire ART treatment period in a rapid and cost-effective single-step process. In this Phase II SBIR project, we propose to build on our existing data from Phase I to optimize a progesterone IVR named AnelleO-PRO, test its efficacy in a relevant macaque model, and conduct IND-enabling studies to support an IND-application. We will implement comprehensive rational IVR design, using the highly relevant preclinical sheep and macaque models to characterize the safety, pharmacokinetic profiles, and efficacy of optimized AnelleO-PRO. This multidisciplinary, cutting-edge approach will develop a unique and highly innovative 3D printed CLIP IVR – AnelleO-PRO, delivering progesterone in a long-acting, single administration treatment of infertility.The benefit of sustained release of progesterone to women who undergo infertility treatment is highly significant. Long-acting intravaginal formulations providing steady release of progesterone over several weeks can increase compliance to ART regimens, providing a patient friendly modality that could transform the ART landscape. The overarching goal of this proposal is to develop and evaluate an innovative approach to creating and manufacturing intravaginal rings that can contribute to curbing infertility - a significant global medical need.