Development of an ultrapotent anti-sperm antibody construct for non-hormonal contraception

Mucommune, Llc, Morrisville NC

Investigators

Abstract

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 antibody (ASA) that agglutinates and traps sperm in mucus, thereby preventing sperm from reaching the egg. We were part of a consortium that advanced the very first ASA into exploratory clinical studies, where we showed a high dose of ASA (HC4 IgG) given immediately before intercourse was highly effective at eliminating progressively motile sperm in the cervix. To further improve potency and create a product that offers sustained contraception, we previously developed a multimeric contraceptive antibody, FFIFF, which targets the same well characterized and validated sperm epitope as HC4 IgG, and could 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 could stably release FFIFF and provide virtually complete sperm agglutination in sheep for over 20 days (more than adequate to cover the fertility window in most women). More recently, we have engineered a next-generation ASA, LamH10, which possess even greater avidity and potency against sperm at physiological temperature (37oC), exceeding the activity of the parent HC4 IgG by orders of magnitude. To validate and advance LamH10 as the contraceptive antibody for our capsule-IVR platform, we will formulate LamH10 into IVR and characterize both the release kinetics and activity/stability of released LamH10 in R61 Aim 1. We will then advance the LamH10-IVR into sheep study where we will assess the safety and sperm- agglutinating potency across our targeted fertility window in R61 Aim 2. If we meet the R61 milestones by validating the safety and effectiveness of LamH10-IVR as well as a cGMP cell line compatible with GMP manufacturing of LamH10, we will focus the R33 phase on pre-IND filing (R33 Aim 1) and manufacturing of GMP-grade materials (R33 Aim 2). Successful completion of these activities, combined with our other ongong efforts, will put us in position to quickly advance LamH10-IVR into clinical study after the completion of this project. This project represents a major milestone in our efforts to advance LamH10-IVR into the clinic to address a significant unmet need in the contraceptive marketplace.