PROJECT ONE: ABSTRACT The purpose of the Industrialization Project is to manufacture an antibody-based product for use in women to achieve contraception. The Human Contraceptive Antibody (HCA) will be formulated in a vaginal film for on- demand protection, and in an intravaginal ring (IVR) for long-term protection. The addition of antibody-based contraception will be the commercial driver for a more comprehensive future version of MB66 (anti-HIV/HSV), an antibody-based multipurpose prevention technology (MPT) that is currently in a Phase 1 safety trial. Because of their potency, specificity, and safety profile, human monoclonal antibodies (mAbs) are leading candidates for the generation of highly specific, but mechanistically diverse, contraceptive MPTs. The industrialization process of HCA (a Contraception Development Research Project) is turning a laboratory process into a consistent and well-characterized process that can mass-produce a quality product. The challenges involved in successful industrialization are complex, though highly underestimated in the scientific community. Fortunately, manufacturing platforms for monoclonal antibodies have made significant technical and therapeutic advances over the last several decades. Although each platform may offer some manufacturing advantages, only Nicotiana and Trichoderma are likely to be able to address the unmet needs of large, cost-sensitive markets like antibody-based contraceptives. The near-term driving factors for the Industrialization Project are speed, quality and research costs favoring transient expression of fully assembled antibodies in the plant Nicotiana, while the long-term drivers for large, cost-sensitive markets are rapid cycle time (days to weeks), low commercial manufacturing cost (<$10/g of DS), and large commercial scale (>10 metric tons of DS) favoring antibody expression in the fungus Trichoderma.
The Specific Aims of Project One are: 1. To manufacture GMP HCA drug substance (DS) in Nicotiana, and an HCA-film (drug product, DP) for preclinical and clinical studies. 2. To conduct IND-enabling preclinical studies of HCA film. 3. To develop sustained release capsules of HCA that can be incorporated in to intravaginal rings. 4. To industrialize low cost and large-scale Trichoderma manufacturing for an antibody-based Contraceptive MPT.
