VAX014 for Instillation is a proprietary recombinant non-antibody targeted rBMC product formulated for use in the treatment of Non-muscle Invasive Bladder Cancer (NMIBC). The Investigational New Drug application (IND) for VAX014 for Instillation has been submitted to the United States Food and Drug Administration and a Phase 1 clinical trial in patients with NMIBC is under way. For more information about the Phase 1 clinical trial in NMIBC, please click here.
VAX014 is a novel rBMC-based tumor selective oncolytic immunotherapy. VAX014 rBMCs are engineered to express and display the alpha3beta1(α3β1) and alpha5beta1 (α5β1) integrin-targeting protein,Invasin, as well as a novel oncolytic cholesterol-dependent membrane pore-forming toxin payload, Perfringolysin O (PFO). Numerous preclinical pharmacology studies with VAX014 (published under the discovery name "VAX-IP") demonstrate the rapid, irreversible integrin-dependent oncolytic activity of this novel rBMC formulation. Vaxiion has demonstrated the broad spectrum potency and oncolytic activity of VAX014 against multiple integrin-expressing human urothelial carcinoma and other cancer cell lines in vitro. In preclinical mouse models of bladder and other cancer types, VAX014 confers a significant survival advantage with complete tumor regressions while establishing long-term anti-tumor immunologic memory when administered as a single agent.
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 clinical trials in patients with 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