Project Grant R41CA271851

LOW COST, BROAD SPECTRUM CANCER VACCINE TARGETING HUMAN PAPILLOMAVIRUS - PROJECT SUMMARY. HUMAN PAPILLOMAVIRUS (HPV) IS A MAJOR PUBLIC HEALTH CONCERN DUE TO 1) ITS IMPLICATION IN CANCERS OF THE ANUS, CERVIX, OROPHARYNX, PENIS, VULVA, AND VAGINA; 2) GLOBAL ECONOMIC BURDEN, AND 3) VASTLY DISPROPORTIONATE IMPACT ON LOW-TO-MIDDLE-INCOME COUNTRIES (LMIC). HPV-RELATED CANCERS ARE RESPONSIBLE FOR 4.5% OF ALL NEW CANCER CASES WORLDWIDE, 90% OF HPV-RELATED CERVICAL CANCER DEATHS OCCUR IN LMIC, AND ONLY 1% OF LMIC HAVE VACCINATION PROGRAMS WITH LIMITED BREADTH OF PROTECTION. THE MOST BROADLY PROTECTIVE VACCINE ON THE MARKET, MERCK'S GARDASIL-9, ONLY PROTECTS AGAINST NINE HPV STRAINS AND DOES NOT PROTECT AGAINST STRAINS THAT ARE PREVALENT IN LMIC. CURRENT VACCINES ARE ALSO COSTLY AND CHALLENGING TO DISTRIBUTE TO LMIC DUE TO THEIR THERMAL STABILITY AND 3-DOSE REGIMEN. THE LIMITATIONS OF CURRENT VACCINES AND BURDEN OF HPV ON LMIC UNDERSCORES THE NEED FOR NEW CHEAPER HPV VACCINES THAT CAN BE EFFECTIVELY DEPLOYED IN LMIC. VAXSYNA, INC ADDRESSES THIS NEED WITH A HPV VACCINE THAT IS LOW-COST, BROADLY PROTECTIVE, AND EFFICACIOUS WITH A TARGETED TWO- DOSE SCHEDULE. OUR VACCINE CANDIDATE DISPLAYS THE HIGHLY CONSERVED HPV L2 ANTIGEN ON OUR PATENTED PLATFORM THAT USES VIRUS LIKE PARTICLES (VLP) AND RECOMBINANT IMMUNE COMPLEXES (RIC). THE HPV L2 ANTIGEN HAS BEEN SHOWN TO PROTECT AGAINST UP TO 22 TYPES OF HPV IN MICE AND RABBITS AND HAS BEEN EVALUATED IN HUMAN PHASE I TRIALS. OUR VACCINE IS PRODUCED USING AN OPTIMIZED PLANT EXPRESSION SYSTEM THAT LOWERS THE MANUFACTURING COST (ESTIMATED AT LESS THAN $0.5/DOSE VS. $160/DOSE FOR GARDASIL-9), THEREBY PRODUCING HIGH LEVELS OF PROTEINS IN 4-5 DAYS WITHOUT HUMAN OR ANIMAL PATHOGEN CONTAMINATION. PRECLINICAL, MOUSE VACCINATION STUDIES WITH OUR CANDIDATE HAVE CONFIRMED ITS EFFICACY IN GENERATING HIGH ANTIBODY TITERS AND VIRAL NEUTRALIZATION IN AS LITTLE AS TWO DOSES. FURTHER TESTS OF OUR VACCINE PLATFORM HAVE SHOWN THAT PROTECTIVE IMMUNITY IS POSSIBLE WITHOUT THE NEED OF A CHEMICAL ADJUVANT. THE GOAL OF OUR STTR PHASE I PROJECT IS TO CONDUCT PROOF-OF-CONCEPT STUDIES TO CHARACTERIZE THE FORMULATION OF VAXSYNA'S HPV CANCER VACCINE AS A BROAD-SPECTRUM HPV VACCINE THAT TARGETS ALL CLINICALLY RELEVANT HPVS. TEMPERATURE STABILITY IS AN IMPORTANT CHARACTERISTIC FOR VACCINES THAT ARE TARGETED FOR LMIC. AS SUCH, OUR PARENT AWARD AIM 1 WILL ASSESS THE THERMAL STABILITY OF BOTH OUR VLP AND RIC VACCINE COMPONENTS. FOR THE PARENT WARD AIM 2 WILL COMPARE THE ANTIBODY AND NEUTRALIZING ANTIBODY TITERS PRODUCED AFTER MOUSE VACCINATION WITH VARYING RATIOS OF VLP TO RIC AS COMPARED TO GARDASIL-9. PROPOSED ADMINISTRATIVE SUPPLEMENT AIM 3 WILL EVALUATE THE SUCCESS OF VAXSYNA'S HPV VACCINE TO CONFER PROTECTIVE IMMUNITY AGAINST COTTONTAIL RABBIT PAPILLOMAVIRUS IN THE HPV-STANDARD ANIMAL MODEL NEW ZEALAND WHITE RABBITS BY MEASURING ANTIBODY, NEUTRALIZING ANTIBODY, CELLULAR RESPONSES, AND PAPILLOMA GEOMETRIC VOLUME. THE SUCCESSFUL COMPLETION OF THIS PHASE I PROJECT IS CRITICAL TO INITIATE OUR PROPOSED PHASE II STUDIES INVOLVING PRE-IND GMP MANUFACTURING AND ANIMAL TOXICOLOGY STUDIES. UPON SUCCESSFUL APPROVAL OF VAXSYNA'S HPV VACCINE, OUR ADVANTAGES OF LOW COSTS AND BROAD-SPECTRUM PROTECTION WILL POSITION VAXSYNA TO PREVENT HPV-CAUSED CANCERS FOR INDIVIDUALS IN LMIC.