Project Summary The goal of PathoVax’s SBIR Phase 1 project is to further develop the potential and global applicability of RGVaxTM, a broad spectrum universal HPV vaccine. RGVaxTM is currently a single chimeric HPV virus-like particle (VLP) platform that displays 360 copies of the highly conserved, neutralizing HPV epitope (RG1). Animal vaccination studies confirmed broad-spectrum protection (via RG-1 cross neutralizing antibodies) against clinically relevant 27 HPVs. This dramatic improvement over licensed HPV vaccines led to an National Cancer Institute (NCI) PREVENT award that funds GMP, toxicology and an IND application for Phase 1 (expected Q1 2020). To enhance the odds of market success, PathoVax sought discussions with HPV key opinion leaders and has learnt that the practical impact of RGVax upon licensure can be compromised by vaccine implementation challenges such as (1) multiple immunizations and (2) instability due to refrigeration requirements. As such, PathoVax is furthering the current RGVaxTM formulation via a Thermostablizing-Atomic Layer Deposition (TALD) process. TALD first converts aluminum adjuvanted RGVaxTM into a thermostable lyophilized glassy powder. This powder is subsequently utilized as a core which undergoes at least another 100 cycles of nanometer-thick layering of aluminium adjuvant on its surface via Atomic Layer Deposition (ALD). Subsequently, a second, outer layer of lyophilized RGVax may be adsorbed to the aluminum-coated RGVax particles. This new formulation, termed “TALD-RGVax” can then be administered as a single injection whereby the outer layer of antigen and the aluminum-based coating will act as the conventional primary dose. Following 20-120 days, tunable by adjusting the number of coats, sufficient coating will dissolve, allowing release of the core antigen to serve to as a booster. TALD is able to convert aluminum adjuvant-formulated vaccine into a thermostable form without compromising immunogenicity (most lyophilization processes require freezing and this affects the stability of pre-formulated adjuvant vaccines). Additionally, although administered as a single injection, by virtue of the ALD process TALD-RGVax provides a prime and boost vaccination. Aim 1 is focused on developing a robust primary protocol to readily generate TALD-RGVax (with different parameters, e.g. different ALD coating deposits) and study it’s subsequent in vitro conformation and temperature stability, and in murine models its immunogenicity. Aim 2 focuses on benchmarking the top 3 lead TALD-RGVax formulations based on the parameters and findings in Aim 1. Efficacy of these lead TALD- candidates will be tested against Gardasil-9®, the current standard of care for HPV prevention. Vaccination studies will be performed using animal models which validated the current Gardasil vaccine franchise. Together, these studies will systematically define key TALD-RGVax parameters that will eventually lead to an optimized TALD-RGVax formulation and process strategy for SBIR phase 2.

PROJECT NARRATIVE PathoVax is developing the world’s 1st single immunization, thermostable, broad spectrum universal Human Papillomavirus (HPV) Vaccine. The scientific and commercial merits of RGVax™ will offer the opportunity to (1) prevent various forms of HPV-associated cancers and disease and (2) address vaccine implementation issues such as cold chain storage and patient compliance which burden both developed and developing country’s healthcare systems. This vaccine will potentially also drive up immunization rates for future generations to be free from HPV infections, and one may envision a healthcare system where there is no controversial stigma towards a cancer-preventative vaccine as well as the need for regular Pap screening being diminished.