Fast Dissolving MM008 Tablet for Instant On-Demand Non-Hormonal Contraception

Project 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 strong aversion to using exogenous hormones, due to real and/or perceived side effects. Furthermore, women’s contraceptive preferences are diverse: while some strongly prefer the convenience and sustained contraceptive activity of an intravaginal ring (IVR), others strongly prefer discrete methods that can be used on-demand during infrequent intercourse. Thus, a suitable delivery format is equally important as the underlying contraceptive mechanism. Current on-demand contraceptive options, such as gels/films/condoms, each faces substantial limitations, including limited effectiveness, substantial toxicity, and/or inconvenient dosing timing and format. A non-hormonal contraceptive that is fast-acting with prolonged (i.e. many hours of) activity, safe, effective, not messy and discreet would meet the needs of many women seeking on-demand contraception, but are not met by any of the currently available contraceptive products. We are creating such a non-hormonal contraceptive (product code: MM008) by formulating Mucommune’s proprietary highly multivalent anti-sperm monoclonal antibodies (mAb) into fast dissolving antibody tablets (FDATs). We previously developed a mAb termed FFIFF that binds a well-characterized and validated antigen target present only on human sperm and cells from the male reproductive tract, but are otherwise absent in all tissues in women. Due to its highly multivalent nature, FFIFF potently agglutinate and trap sperm in CVM (>16-fold greater than parent HC4 mAb in standard IgG format), thus effectively preventing individual progressively motile sperm from reaching the egg. More recently, we engineered an improved molecule termed LamH10, which possess even greater avidity and potency against sperm at physiological temperature (37˚C), exceeding the activity of the parent HC4 IgG by over 100-fold. We have also successfully formulated LamH10-FDATs, comprised of a proprietary blend of safe and routinely used excipients, with rapid disintegration (<2 min) and high contraceptive efficacy in human cervicovaginal mucus (CVM) that, in pilot sheep studies, reduced progressively motile sperm by >99.9% in the sheep vagina within <5 mins of tablet insertion. LamH10 is the lead MM008 molecule. Building off of these promising results, we seek to quickly advance MM008-FDAT through IND-enabling preclinical studies. We will develop cGMP production processes that necessary support the manufacturing of FDATs for IND-enabling and Phase 1-2 studies (Aim 1A), and file and receive feedback from the FDA on a Type B pre-IND submission (Aim 1B). We will produce tox materials and complete GLP vaginal tox studies and rabbit vaginal irritation studies following FDA guidance (Aim 2). Successful completion of these aims will put us in a position to file IND for MM008-FDAT pending manufacturing of clinical trial materials, and solidify the foundation for future contraceptive products being developed at Mucommune.