Project 1: Industrialization of ZB-06

PROJECT 1 - ABSTRACT The purpose of the Industrialization Project, and of the entire P50 CRC program, is to develop an antibody-based, woman-controlled contraceptive. This proposal is part of a long-term project to develop and commercialize an antibody-based contraceptive (stand alone product), and a multipurpose prevention technology (MPT) that includes a contraceptive monoclonal antibody (mAb) as well as mAbs against sexually transmitted diseases. Two previous NICHD/NIAID grants supported manufacturing and clinical testing of intravaginal films that were stages in the developmental pathway to an MPT. In the first grant we developed MB66, a vaginal film that contained monoclonal antibodies (mAb) against HIV and HSV. The Phase 1 clinical trial of MB66 showed that it was safe and well tolerated, and that vaginal samples collected up to 24 hours after MB66 insertion significantly neutralized both HIV-1 and HSV-2 ex vivo. The second grant funded an ongoing proof-of-concept trial of ZB-06, a film that contains HCA, a monoclonal antibody that targets CD52g, a male reproductive tract glycoprotein. CD52g coats sperm, and when HCA binds to CD52g it results in agglutination and mucus trapping of sperm. Preliminary results from the ongoing trial of the ZB-06 indicate that it is effective at drastically decreasing the number of progressively motile sperm that reach the upper cervix when administered ~30 minutes prior to intercourse (a post-coital test, PCT). The ongoing Phase 1 clinical trial of ZB-06 was carried out under an exploratory IND that allowed us to test the the surrogate efficacy of ZB-06, but was not a standard safety Phase 1. Given the positive surrogate efficacy results from the ongoing study, we now propose to carry out the Phase 1 safety trial required for further development of ZB-06 and a dose ranging Phase 2 study. Project 1 will be responsible for the manufacture of the HCA Drug Substance (DS) and ZB-06 Drug Product (DP), the IND enabling toxicology studies of ZB-06, and regulatory and quality support for the manufacturing and clinical trial. While HCA DS and ZB-06 DP were manufactured previously for the proof of concept Phase 1, the Drug Product manufacture was done at lab scale. We will now develop a commercializable ZB-06 manufacturing process; the manufacturing, release testing and stability programs will take advantage of (and be de-risked by) our previous experience with MB66 and ZB-06, including FDA guidance. Similarly, our nonclinical toxicology program is based on our previous experience with MB66 and ZB-06. Finally, the ZabBio team will provide regulatory and quality oversight for this project as they have done for the two previous trials, and pursue commercialization of an antibody-based contraceptive.