IND-enabling preclinical development of a multipurpose intravaginal ring for the prevention of Herpes, HIV and unintended pregnancy

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SUMMARY The broad, long-term goal is to empower women to protect themselves from HIV and herpes infections, and unintended pregnancy through the development of a monthly intravaginal ring (IVR) formulation. The IVR utilizes our proprietary Versa™ technology that enables simultaneous, sustained release of the antiretrovirals of Truvada® (tenofovir disoproxil fumarate-emtricitabine combination) for HIV pre-exposure prophylaxis, an antiviral, acyclovir, for prevention and treatment of herpes and; the hormonal contraceptives of the Nuvaring® (etonogestrel-ethinyl estradiol) for the prevention of unintended pregnancy. These drugs have been tested in our IVR technology in vitro and in vivo. We now propose the translation of this work to our pod-based™ IVR technology to utilize an achievable regulatory approach for approval of multipurpose prevention IVRs. This RFA-AI-16-085 provides Auritec with a unique opportunity to perform both, mid-stage and late-stage translational work through a milestone-driven IND-enabling approach that will further the development of an IVR-based MPT for the prevention of both HIV and HSV infections, and unintended pregnancies. In the R61 Phase of this grant, we propose the following mid-stage translational specific aims: 1) to develop small scale, “exploratory” GMP manufacturing capacity for the lead formulations; 2) to perform a non-GLP safety and PK study in the standard sheep model. The milestone for the successful completion of the R61 Phase is the demonstration of safety and clinically relevant pharmacokinetics in the non-GLP sheep study. The R33 Phase comprises the following late-stage translational specific aims: 3) to conduct an IND-enabling GLP-compliant safety study in a sheep model to examine local/systemic toxicity; 4) to perform manufacturing process development, including product testing assays and early validation; 5) to transfer manufacturing and analytical methods to a contract manufacturing organization; 6) to perform IND-enabling chemistry, manufacturing and controls (CMC) activities for three IND submissions; 7) to coordinate all activities to submit three IND applications to the FDA The milestones for the successful completion of the R33 Phase of this proposal is the submission of three IND applications (TDF-FTC pods, ACV pods and ETG-EE pods) to the FDA to perform first-in-human exploratory clinical trials. Following successful completion of this proposal we will carry out the clinical protocols to demonstrate safety and pharmacokinetics for the three rings. Further funding from granting agencies will be sought at that point but licensing to a corporate partner with the resources to ensure ultimate approval and commercialization will also be actively pursued. The development of these ring could provide women of child bearing age, for the first time, a women-controlled dual protection against unwanted pregnancy, genital herpes, and HIV infection.