IND‐enabling development of MM‐008 IVR, an antibody-based nonhormonal contraceptive intravaginal ring

总结

Summary Nearly half of all pregnancies in the U.S. are unintended, and most occur in women who are not using contraceptives. There are diverse reasons for not using contraceptives; one common reason is that many women have a strong aversion to using exogenous hormones due to real and perceived side effects. It is likely that contraceptive use and satisfaction would substantially increase if there were a non-hormonal, user- controlled contraceptive method that does not require coitally-timed actions nor daily dosing. Such product does not currently exist. We believe we can create such a non-hormonal contraceptive based on an intravaginal ring (IVR) releasing an anti-sperm monoclonal antibody (mAb) that agglutinates and traps sperm in mucus, thereby preventing sperm from reaching the egg. Topical passive immunization based on vaginal delivery of anti-sperm Ab was validated in animal models in the 80’s-90’s, and directly overcomes the variable intensity and uncertain reversibility of contraceptive vaccines. However, this strategy was not practical until recently due to the high costs of mAb production, and modest agglutination potencies of IgG. Given the remarkable advances in bioprocessing that have greatly reduced the manufacturing costs of mAb, we believe the time is now ripe to develop an IVR for sustained passive immunization of the vagina with a potent anti-sperm mAb. We possess an exceptionally potent antibody, MM008, that target a well characterized and validated antigen target present on human sperm, is highly homogeneous and stable, and can reduce progressively motile sperm by 99.9% in the sheep vagina in 2 mins at a dose of just 33 ug per sheep. We have also developed a proprietary capsule-IVR system that can stably release MM008 for over 20 days (more than adequate to cover the fertility window in most women). In pilot studies, MM008-IVR was able to provide complete sperm agglutination in the sheep vagina for over 21 days. Building off of these promising results, we seek to establish in Aim 1 the cGMP production processes that will support the manufacturing of capsule-IVR for IND-enabling and Phase 1-2 studies, and validate the capsule-IVR can provide sustained release of MM008 in vitro and in vivo. We will then perform in Aim 2 a usability and safety assessment of a placebo capsule-IVR in women. Finally, we will complete in Aim 3 other critical path IND-enabling activities, including GLP TCR and GLP Biocompatibility studies. Successful completion of these activities will put us in position to file IND for MM008-IVR quickly after the manufacturing and release of the MM008 clinical trial materials. This project is designed to support clinical evaluation of our non-hormonal contraceptive MM008- IVR that could address a significant unmet need in the marketplace, and lay the foundation for future multifuntional IVRs that also protects against STIs.