Project 3: Film Formulation, PK/PD and Safety Studies of ZB-06

PROJECT 3 - ABSTRACT The primary objectives of Project 3 are to optimize the vaginal film delivery system for the Human Contraception Antibody (HCA) and to perform assays to assess PK/PD and safety endpoints in vaginal samples from women in the clinical trials. Vaginal film optimization will be conducted by Dr. Rohan at the University of Pittsburgh. The first step will be to optimize the immediate-release film that will be used in the clinical trials; Dr. Rohan will oversee transfer of film production to KBio, the company that will manufacture the GMP HCA film. The next step will be the development of an extended-release film that will deliver contraceptive antibody for > 3 days. Antibody studies for the film optimization work and for the clinical PK/PD trial will be conducted in Dr. Anderson’s laboratory. Both HCA antibody concentration and activity will be assessed. In addition, Dr. Anderson’s laboratory will evaluate safety endpoints in women enrolled in the clinical trials. The Specific Aims of Project 3 are: 1) Develop improved vaginal film formulations for immediate and extended HCA release. 2) Evaluate exploratory PK/PD endpoints using innovative assays that measure HCA concentrations and activity in vaginal samples before and after film use. 3) Assess exploratory safety endpoints (vaginal inflammation, changes in the vaginal microbiome and gene expression pathways, de novo development of antisperm immunity) in women before and after HCA film use. We expect that data from these experiments will guide decisions concerning critical parameters of product format, safety and dose that will be invaluable for the progression of ZB-06 through clinical trials and commercialization.