Preclinical development of VAX024 - a novel targeted combination STING agonist/oncolytic agent

PROJECT SUMMARY Vaxiion Therapeutics (www.vaxiion.com) is proposing to develop VAX024, a novel, second generation recombinant bacterial minicell (rBMC)-based targeted oncolytic in situ immunization (ISI) agent purpose-built to work in STING-positive solid tumors. ISI agents are an emerging class of immunotherapies that use the patient’s own tumor while still in place to generate first a local innate immune response that is followed by a systemic antitumor immune response and durable protective immunologic memory. Oncolytic viral therapies (OVs) have paved the road for ISI agents and have demonstrated clinical activity as evidenced by the market approval of IMLYGIC™. However, Imlygic and other OVs suffer from two insurmountable limitations: (1) their activity is severely limited in tumors expressing Stimulator of interferon genes (STING), and (2) they require pharmacies to have BSL-2 capabilities for clinical preparation, the scarcity of which limits patient access to OVs. In addition, OVs have a negative impact on quality of life for patients who must continue collecting, storing, and returning wound dressings, bleaching their toilets after use, and who are not allowed be around immunocompromised or pregnant family members while on therapy. As described herein, VAX024 circumvents the limitations of OVs in a single product concept by leveraging our proprietary rBMC delivery technology to generate a sterile, user- friendly oncolytic agent that is also equipped with a potent clinically validated pan-allelic STING agonist. The value proposition of VAX024 is a first-in-class oncolytic agent specifically designed to work in STING positive solid tumors while broadening patient access in comparison to OVs. Our preliminary work demonstrates a high prevalence of STING expression across solid tumor indications where it is significantly correlated with better progression free survival. The foundational premise and construction of VAX024 has already been demonstrated in preliminary in vitro experiments. The overarching purpose of this SBIR Phase 1 proposal is to generate IND- enabling in vivo proof-of-concept and proof-of-mechanism data, as well as establishing some of the CMC methodologies that will be needed to support an IND for VAX024. Our team has already brought a first generation rBMC-based targeted oncolytic agent to the clinic and will leverage our experience and talent to quickly propel VAX024 through IND submission and into patients.