PREVENT PROGRAM OVERVIEW & PROGRESS
The PREVENT Program is an integrated preclinical-clinical research and development effort supported by a multi-year grant from the National Institute of Allergy and Infectious Diseases (NIAID) to develop novel safe and effective rectal microbicides based on plant-produced natural viral entry inhibitors. Microbicides can help minimize the risk of sexually transmitted infections (STI), in particular the co-transmission of HIV-1, HSV-2 and HCV during unprotected vaginal or anal intercourse. The PREVENT clinical study will assess the utility of new technologies that we are developing to satisfy unmet needs observed in prior clinical and non-human primate (NHP) studies with microbicides.
The Program is led and managed by the University of Louisville in collaboration with some of the world's leading institutions and organizations, including the University of Pittsburgh Medical Center and Magee-Women's Research Institute, the US Centers for Disease Control and Prevention (CDC), University of Maryland, University of Manitoba and Karolinska Institutet, with participation and support from public and private organizations and contractors, including Intrucept Biomedicine, Kentucky BioProcessing, CBR International, SRI International and others. A stellar Scientific Advisory Board comprised of scientists and clinicians from NIAID, National Cancer Institute, MAPP Biopharmaceuticals and NWJ Group help guide the Program towards successful completion of its key milestones.
The Program's lead candidate consists of the naturally occurring protein griffithsin, which was originally isolated from the red alga Griffithsia (top, left) found in the South Pacific Ocean. Griffithsin (structure at top, right) is one of the most powerful, broad-spectrum antivirals ever tested and its activity is under study for potential therapeutic applications against several viral pathogens. For applications in this Program, griffithsin is manufactured in Nicotiana plants to ensure a steady supply of the protein without environmental or ecological consequences. For use as a microbicide active ingredient in the PREVENT clinical study, the native griffithsin protein has been modified slightly to improve its stability. The improved variant is named Q-Griffithsin, or Q-GRFT for short. Plant-produced Q-GRFT can be formulated into a number of delivery vehicles, including gels, films, suppositories and even simple enemas or rinses.
The immediate goal of the PREVENT Program is to assess Q-GRFT's safety, tolerability and acceptability in a first-in-human clinical study with men and women volunteers. The Program was initiated in mid-2014 and to date has accomplished a number of important milestones. These include establishing a proprietary and cGMP-compliant plant-based manufacturing process for Q-GRFT, formulation of the drug in various dosage forms, verification of pharmacokinetic (PK) and pharmacodynamic (PD) criteria to control HIV via topical administration, and quantitation of HIV antiviral potency in a range of assays ex vivo and in vitro. The safety of our Q-GRFT microbicide product was assessed in GLP-compliant multi-species toxicity studies designed to support the upcoming clinical trial. The Program is on track to initiate the Phase I PREVENT Study in 2019. The results of this first study will inform the next stages of Q-GRFT's clinical and regulatory development.