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

创新 3D 打印阴道环 AnelleO-PRO，首个单次注射黄体酮治疗不孕症

• 批准号: 10760954
• 负责人: Soumya Rahima Benhabbour
• 金额: $ 157.02万
• 依托单位: ANELLEO, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10760954
• 关键词: 3-Dimensional; 3D Print; Accelerated Phase; Address; Adherence; Affect; Animal Model; Assisted Reproductive Technology; Atopobium vaginae; Autopsy; Behavioral; Characteristics; Clinical Pathology; Clinical Research; Clinical Trials; Computer-Aided Design; Couples; Data; Development; Development Plans; Devices; Dimensions; Dose; Drug Delivery Systems; Drug Kinetics; Drug Targeting; Engineering; Evaluation; FDA approved; Fertilization in Vitro; Fostering; Friends; Grant; Histopathology; Human; In Vitro; Infertility; Injections; Learning; Light; Link; Liquid substance; Mechanics; Medical; Methods; Pain; Patients; Perception; Performance; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Phase; Pregnancy; Preparation; Process; Production; Progesterone; Property; Quality Control; Research Design; Resolution; Resources; Route; Safety; Sheep; Site; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Supplementation; Surface; Surface Properties; Systems Development; Technology; Testing; Tissues; United States; Vagina; Vaginal Discharge; Vaginal Gel; Vaginal Ring; Woman; Women' s Health; Work; aged; commercialization; compliance behavior; controlled release; cost effective; design; digital; drug release kinetics; fabrication; health application; improved; in vitro testing; in vivo; infertility treatment; innovation; innovative technologies; manufacture; mechanical properties; next generation; novel; novel strategies; pharmacologic; pre-Investigational New Drug meeting; pre-clinical; preference; quality assurance; rational design; reproductive; response; side effect; skills; stability testing; success; technology development; technology platform; treatment duration

Abstract - Infertility affects ~13-15% of reproductive-aged couples in the US. The success of in vitro fertilization (IVF), the most used Assisted Reproductive Technology (ART), depends on sustained exogenous progesterone supplementation to establish and maintain pregnancy. This supplementation must be administered over 8 to10 weeks of gestation until placental progesterone production is adequate to maintain pregnancy. However, current treatment options such as vaginal gel, inserts, or IM injection, have several drawbacks and side effects that lead to low patient compliance. In response to the critical need for improved products for sustained progesterone supplementation, AnelleO is developing AnelleO-PRO, an intravaginal ring (IVR) delivering progesterone over 28 days to cover the entire ART treatment period (8-10 weeks) with only 2-3 rings. Progesterone supplementation with an IVR provides a patient friendly option for controlled, sustained release of progesterone with less frequent dosing. AnelleO’s next-generation IVR technology is based on a novel approach that applies a state-of-the-art 3D printing technology (Digital Light Synthesis, enabled by continuous liquid interface production, CLIP™) to achieve rapid, cost-effective IVR fabrication for continuous drug release for ART and other applications. AnelleO is applying historical lessons and previous studies on IVRs to address key gaps and needs to yield better products. This Phase IIB project fosters progress made in Phase I and in the ongoing Phase II in an iterative, incisive, rational design process to pave the way to an IND submission. The Specific Aims for this project are: 1) In vivo GLP sheep safety and pharmacokinetic (PK) study. Anelleo will engineer GLP 3D CLIP IVRs with final design selected based on in vitro and in vivo safety data from Phases I and II, and conduct in vitro quality control studies. This Aim also includes in vivo GLP safety and PK in sheep for GLP PRO IVR to mimic clinical study design in human, and in vivo PK for a selected IVR design. 2) IND-enabling studies (10993 ISO testing) for the selected IVR design. Building on FDA guidance from a pre-IND meeting and working with a regulatory team and CDMOs/CROs, AnelleO will engineer a GLP batch of the IVR and conduct IND-enabling testing. 3) Prepare and submit an IND application for AnelleO-PRO. Working with a regulatory team and medical/CMC/preclinical experts, AnelleO will prepare and submit an IND application for AnelleO-PRO. This work is critical for advancing AnelleO-PRO as a safe and equivalent or superior technology to current products used for progesterone supplementation in ART. The pivotal sheep GLP and ISO10993 studies will establish the safety and efficacy of our product for ART and pave the way to clinical trials and commercialization. The development of AnelleO-PRO for sustained delivery of progesterone to cover the entire ART treatment period with only 2-3 ring administrations will be groundbreaking, as there is no FDA approved 3D printed IVR for delivery of natural PRO for ART or any other indication. AnelleO’s IVR platform technology will offer customizable, sustained, and controlled drug delivery of pharmaceuticals via the vaginal route, and thus can also meet a broad range of women’s health applications.

抽象的 - 美国约 13-15% 的育龄夫妇患有不孕症 体外受精 (IVF) 的成功。 最常用的辅助生殖技术（ART），依赖于持续的外源性黄体酮 补充以建立和维持怀孕必须在 8 至 10 天内服用。 妊娠周数直到胎盘产生的黄体酮足以维持妊娠。 阴道凝胶、插入物或肌内注射等治疗方案有一些缺点和副作用，会导致 以满足对持续黄体酮改进产品的迫切需求。 AnelleO 正在开发 AnelleO-PRO，这是一种阴道内环 (IVR)，可在 28 天即可覆盖整个 ART 治疗期（8-10 周），仅补充 2-3 环黄体酮。 IVR 为患者提供了一种患者友好的选择，可控制、持续释放黄体酮，且频率较低 AnelleO 的下一代 IVR 技术基于采用最先进技术的新颖方法。 3D 打印技术（数字光合成，通过连续液体界面生产，CLIP™ 实现） 实现快速、经济高效的 IVR 制造，以实现 ART 和其他应用的连续药物释放。 正在应用 IVR 的历史教训和先前的研究来解决关键差距和需求，以取得更好的成果 该IIB阶段项目以迭代的方式促进第一阶段和正在进行的第二阶段取得的进展。 深入、合理的设计流程，为 IND 提交铺平道路 该项目的具体目标是：1) Anelleo 将设计 GLP 3D CLIP IVR 进行最终的羊体内 GLP 安全性和药代动力学 (PK) 研究。 根据I期和II期的体外和体内安全性数据选择设计，并进行体外质量控制 该目标还包括 GLP PRO IVR 的绵羊体内 GLP 安全性和 PK 模拟临床研究。 人体设计，以及所选 IVR 设计的体内 PK 2) IND 支持研究（10993 ISO 测试）。 根据 IND 前会议的 FDA 指导并与监管团队合作，选择了 IVR 设计。 CDMO/CRO，AnelleO 将设计 IVR 的 GLP 批次并进行 IND 验证测试 3) 准备和进行。 与监管团队和医疗/CMC/临床前合作提交 AnelleO-PRO 的 IND 申请。 专家们表示，AnelleO 将准备并提交 AnelleO-PRO 的 IND 申请，这项工作对于推进至关重要。 AnelleO-PRO 是一种安全且与当前用于黄体酮的产品相当或优越的技术 关键的绵羊 GLP 和 ISO10993 研究将确定 ART 补充剂的安全性和有效性。 我们的产品用于 ART 并为 AnelleO-PRO 的临床试验和商业化铺平道路。 只需 2-3 环即可持续输送黄体酮，覆盖整个 ART 治疗期 这将是开创性的，因为目前还没有 FDA 批准的 3D 打印 IVR 来为 ART 或任何其他药物提供天然 PRO AnelleO 的 IVR 平台技术将提供可定制、持续和受控的药物。 通过阴道途径输送药物，因此也可以满足广泛的女性健康需求 应用程序。