Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIV

SummaryThere is a critical need for improved methods for both contraception and HIV preventionNearly half of all pregnancies in the U Sare unintendedand globally there are andgtmillion unintended pregnancies andmillion new HIV infections each yearNot surprisinglyunintended pregnancies occur most often in women who are non users of contraceptionmany women are averse to using exogenous hormones due to real and perceived side effectsand frequently discontinue hormonal contraceptionThis underscores the need for a non hormonal contraceptive method that does not require coitally timed actionsnor daily interventionWe believe adding contraception to an HIV prevention method would also strongly improve user adherencesince few couples self identify as at risk of HIVwhile nearly all self identify as at risk of pregnancyInspired by naturewhere some infertile women express antibodies that bind surface antigens on sperm and block sperm penetration through their cervical mucuswe have investigated a fully human monoclonal antibodymAbthat can quickly bind a unique antigen present only on the surface of human spermwe refer to this mAb as human contraceptive antibodyHCAImportantlyHCA agglutinated andgtof sperm within seconds in allfresh semen samples tested from men spanning diverse demographicsA similiar mAb that binds rabbit sperm reduced egg fertilization byin the highly fertile rabbit modelMajor strides have been made with discovering and testing broadly neutralizing mAbbnAbagainst HIVincluding protection against vaginal HIV transmissionIndeedmembers of our team led the first clinical trial of VRCdelivered vaginallyTo realize the vision of a mAb based MPT productthe next step in our development is toiformulate mAb into a delivery system that maintains effective levels of mAb in the female reproductive tractandiifurther validate efficacy in large animal modelsThusduring Phase I of this Fast Track applicationwe will formulate sustained release polymeric capsules encapsulating a cocktail of mAbsHCA and VRCNfor HIV preventionand can be embedded into intravaginal ringsIVRThe goal is to demonstrate that loaded mAbs will remain sufficiently stable and activeneutralize trap HIV and agglutinate trap spermwhen exposed and released into human cervicovaginal secretions over aday periodPending successful completion of Phase I milestonewe will perform repeated low dose vaginal SHIV challenges to confirm if mAb released from the engineered polymeric capsules can effectively reduce vaginal transmissionIf successfulour proposed work will strongly support clinical development of our combination contraceptive and HIV prevention MPT IVR that could address a major unmet need in the marketplace Narrative Statement Preventing unintended pregnancies and HIV transmission are both major public health prioritiesHerewe will develop our capsule intravaginal ringIVRtechnology for sustained release ofisperm binding antibody for non hormonal contraception andiiHIV binding antibodies to prevent vaginal HIV transmissionand evaluate their potency in monkeysmacaquesSuccessful completion of this project will enable us to begin clinical development of a combination IVR that offers both non hormonal contraception and HIV prevention