Development of a biologic for non-hormonal contraception

There is a critical need for improved contraceptive methods both in the U Sand worldwideNearly half of all pregnancies in the U Sare unintendedand globally there are overmillion unintended pregnancies each yearUnintended pregnancies represent a $Bcost burden to the health system across the federal and state levels in the U SaloneThe majority of unintended pregnancies are concentrated in women who are non users of contraceptionunderscoring the need for contraceptive methods with greater user acceptability and complianceThrough direct interviews with over a hundred prescribersexperts and key opinion leaders in the contraceptive fieldwe have confirmed that there is a major unmet need for an effectivereversiblenonhormonal and non coitally associated contraceptive methodCurrentlythe only non hormonal option that is also non coitally associated is the copper intrauterine devicewhich often leads to heavy menstruationsignificant cramping and abdominal painInspired by naturewhereby some infertile woman can produce antibodies that bind surface antigens on sperm that block sperm penetration through her cervical mucuswe have investigated a fully human monoclonal antibodymAbthat can quickly bind an antigen present only on the surface of sperm and other cells originating from the male reproductive tractWe refer to this mAb as a human contraceptive antibodyHCAImportantlythe antigen appears to be ubiquitous on human spermas all semen samples frommen spanning diverse demographics were agglutinated by the prototype HCAwith andgtof sperm agglutinated in fresh semen within secondsWe have verified in vivo contraceptive effectiveness of a rabbit sperm binding mAb similar to HCAwhere vaginal delivery of this sperm binding mAb reduced fertilized eggs byDue to notorious variations in the functional performance of mAb produced in different cell systemsto advance our goal of non hormonal contraception based on HCA released from an intravaginal ringIVRthroughout the fertility windowthe next phase in the development cycle is to produce the same mAb using a scalable processIn Aimof this proposalwe seek to develop a high secreting cell line of HCA using DGChinese Hamster Ovary cellsa frequently used platform in industry for scalable production of biologicsWe will verify that HCA produced by stable DGcells maintains the same spermbinding affinity and sperm agglutination and trapping potency compared to HCA produced using transient production methodsIn Aimwe will incorporate HCA into Mucommuneandapos s proprietary capsule IVR designverify that we can release HCA into human cervicovaginal mucus for at leastdaysand measure the sperm agglutination and trapping potencies of the released HCAOur long term goal is to develop a shelf stable nonhormonal contraceptive IVRSuccessful completion of the Phase I aims will lead to a Phase II proposal verifying we can sustain effective contraceptive concentrations in macaquesand further develop the manufacturing platform in preparation for pre IND toxicity and efficacy studies In the U Snearly half of all pregnancies are unintendedwhich represents a cost burden of over $B to the federal and state governmentAmong the contraceptive options availablethere is a lack of effective nonhormonal methods that are also non coitally associatedBuilding off of our promising in vitro and in vivo studieswe seek to develop a production system for a unique human sperm binding monoclonal antibodyand verify that we can stably release the antibody from a vaginal ringSuccessful completion of this project will accelerate the development of a monoclonal antibody based non hormonal contraceptive method that is also non coitally associated