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

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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.