VAX014 for Instillation is a proprietary recombinant non-antibody targeted BMC product formulated for use in the treatment of Non-muscle Invasive Bladder Cancer (NMIBC). The pre-clinical development of VAX014 for Instillation is well under way with submission of the IND to FDA on the near horizon. Clinical trials are slated to begin in NMIBC patients in 2017.
VAX014 BMCs are engineered to express and display the alpha3beta1(α3β1) and alpha5beta1 (α5β1) integrin-targeting protein,Invasin, as well as a novel cholesterol-dependent membrane pore-forming toxin payload, Perfringolysin O (PFO). Numerous pre-clinical pharmacology studies with VAX014 (published under the discovery name "VAX-IP") demonstrate the rapid, irreversible integrin-dependent cell killing activity of this novel BMC formulation. Vaxiion has established the broad spectrum potency and activity of VAX014 against multiple integrin-expressing human urothelial carcinoma cell lines in vitro as well as the ability of VAX014 to confer a significant survival advantage with complete tumor regressions when administered as a single agent in multiple pre-clinical models of bladder cancer in vivo.
VAX014 is differentiated from other integrin-targeted oncology agents because it recognizes and kills only those cells whose α3β1 and α5β1 integrins are found "un-ligated" to their cognate extracellular matrix (ECM) binding partners. In contrast, most first generation integrin-targeted therapeutics are unable to distinguish between ligated and un-ligated integrins. In the context of normal tissues, α3β1 and α5β1 integrins are bound (ligated) to their respective ECM partners, laminin and fibronectin. Disruption of integrin-ECM binding and the presence of un-ligated integrins in normal tissues, typically a result of injury, results in rapid apoptosis-like programmed cell death through a process termed "anoikis". In cancer, aberrant survival signals received as a result of various oncogenic mutations converge to override anoikis, allowing tumor cells to survive detachment from ECM, a critical feature of epithelial-mesenchymal transition, cell migration, tumor metastasis and cancer progression. Therefore, because normal cells cannot survive anoikis due to un-ligated α3β1 and α5β1 integrins but cancer cells can, these un-ligated α3β1 and α5β1 integrins represent attractive tumor-selective pharmacological targets with the potential to have minimal off-target toxicity.
VAX014 for Instillation
VAX014 for Instillation is undergoing preclinical development for use in NMIBC, while VAX014, the underlying API, is being investigated for potential use in other solid tumor types where VAX014 integrin target subtypes are recognized as clinically validated tumor selective targets