Polyionic Papillomavirus like Particles VLP for the Treatment of HPV oropharyngeal squamous cell carcinomas OPCs

The broader impact commercial potential of PathoVax s STTR phase I proposal is to improve outcomes of cancer immuno therapy utilizing a vaccine formulation combining an immunogenic chimeric virus like particle cVLP vaccine with FDA approved immune check point inhibitors PathoVax proposes to develop this technology for treatment of human papillomavirus HPV associated cancers However cancer vaccines have in general shown poor efficacy in clinical trials We contend that their failure reflects inherent deficiencies in cancer vaccine technologies Plasmid DNA vaccines are weakly immunogenic in humans Live viral vectors possess inherent concerns including cross reactive immunity and safety risks for immune compromised individuals Peptides alone are poorly immunogenic and available adjuvants to enhance cellular immune responses have limited efficacy To overcome the challenges faced by immunization and improve the treatment efficacy of immunotherapy PathoVax has developed a novel technology for inducing T cell responses PathoVax s patented VLP with checkpoint inhibitors formulation leverages the current paradigm whereby cancer vaccines are likely to be most effective when combined with checkpoint inhibition There is safety precedent for use of papillomavirus VLPs Gardasil and Cervarix Our VLP technology can prime the intratumoral recruitment of immune cells to sensitize once non inflamed non permissive tumors to both cytotoxic killing and checkpoint inhibitors In preliminary studies we have shown that our cVLPs displaying the HPV E aa Kb restricted epitope induced robust CD T cell responses and demonstrated therapeutic efficacy in the TC C BL mouse tumor model Translation into the clinic will require antigens spanning the full length of HPV E and E proteins Technical objectives of this Phase I proposal are focused on reformulating our vaccine to encompass these E E antigens and characterize our cVLP to ensure a product with consistent features and biological activity upon translation into the clinic Aim We will then utilize this final formulation to assess the efficacy of our characterized formulation in a clinically relevant mouse model of HPV OPC aim Successful implementation of this proposal will be the foundation for additional characterization and GLP efficacy studies in a Phase II STTR to create a robust pre clinical data package for pre IND FDA discussions Positive results in the area of HPV OPSCC valued at US$ M globally will also encourage extension of the technology as a platform to other cancers and infectious agents Importantly it provides a pathway to attract institutional investors or pharmaceutical partners for support beyond the STTR SBIR process This proposal aims to develop PathoVax s polyionic papillomavirus chimeric virus like particle cVLP combined with immune checkpoint inhibitors for Human Papillomavirus HPV associated oropharyngeal OPC cancers Our academic partner s proof of concept studies have shown positive vaccine therapeutic effects against viral associated tumors and we have received feedback from a potentially interested pharmaceutical collaborator on what further studies we would need to perform to initiate potentially a collaboration beyond this STTR This includes characterization studies of our cVLP vaccine utilizing multiple peptides and testing this in combination with checkpoint inhibitors in a relevant clinical model emulating HPV OPCs