Innovative 3D Printed Intravaginal Ring AnelleO-PRO, the first Single Administration of Progesterone for Infertility

项目摘要 不孕症是一个全球性的健康问题。仅在美国，每年约有170万妇女接受不孕症治疗。到 为了改善不孕症治疗，迫切需要促进对患者友好的孕酮方法 辅助生殖技术（ART）。阴道环，其耐受性良好， 女性，对于避孕和激素替代疗法是有效的，并且具有高的患者依从性， 然而，开发有效的IVRs以提供超过7天的孕酮， 由于当前工程工艺的限制和难以控制释放速率， 要求针对特定药物的定制IVR设计。我们的目标是通过革新 阴道环的工程和制造工艺，使用最先进的3D打印工艺 称为连续液体界面生产（CLIP™）。使用自动化CLIP流程，我们可以设计 并制造具有用传统的注塑或挤出无法实现的表面几何形状的IVR， 帮助控制药物释放CLIP使我们能够精确地微调药物的扩散和释放， 接近完全释放，并独立控制IVR机械性能。重要的是，使用CLIP，我们可以 生产IVRs，提供持续释放孕酮，以覆盖整个ART治疗期， 快速且具有成本效益的一步工艺。在第二阶段SBIR项目中，我们建议在现有的基础上， 来自I期的数据，以优化名为AnelleO-PRO的孕酮IVR，测试其在相关猕猴中的疗效 模型，并进行IND使能研究，以支持IND申请。我们将全面实施 合理的IVR设计，使用高度相关的临床前绵羊和猕猴模型来表征安全性， 优化的AnelleO-PRO的药代动力学特征和功效。这种多学科的尖端方法 将开发一个独特的和高度创新的3D打印剪辑IVR - AnelleO-PRO，提供孕酮在一个 长效、单次给药治疗不孕症。

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.