Purple Biotech (PPBT) announced new data regarding its tri-specific antibody platform, CAPTN-3, which were presented at the 36th European Organization for Research and Treatment of Cancer, National Cancer Institute, American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics on October 25, 2024 in Barcelona, Spain. CAPTN-3 is a novel platform technology of conditionally activated tri-specific antibodies engaging both T cells and NK cells to target cancers expressing Tumor Associated Antigen to induce a strong and selective immune response against the tumor. The addition of the NK engager aims to enhances the tumor-killing activity, providing a key differentiation for more sustained and potent anti-tumor effects. The anti-NKG2A arm also acts as a checkpoint inhibitor enabling simultaneous NK and T-cell activation. This scaffold is designed to be activated only at the tumor microenvironment to improve the safety profile and extend the therapeutic index. The capped-alphaCD3 is cleaved by multiple TME-specific proteases, increasing the likelihood of activation by various tumor types. To further extend the capped tribody half-life, human serum albumin is included. CAPTN-3 leverages a plug and play scaffold system providing a flexible design to easily swap and integrate various antibodies to target a wide range of diseases. The platform’s lead compound IM1240 targets 5T4, a TAA expressed in a variety of solid tumors and which is correlated with advanced disease, increased invasiveness, and poor clinical outcome. Purple Biotech’s poster titled “CAPTN-3: A novel platform of conditionally activated T cell and NK cell engagers”, presented the following: The lead compound, IM1240 demonstrated high affinity binding towards CD3 & NKG2A proteins and CD3 & NKG2A expressing cells, while no binding was detected using the mutated versions of the tribody, indicating specificity. The synergistic effects of the alphaCD3 and alphaNKG2A arms in suppressing 5T4+ non-small cell lung cancer patient-derived explant at 10nM were demonstrated, emphasizing CAPTN-3’s potential advantage in a clinically-relevant biological assay. A dose-dependent effect of IM1240 was shown. Sustained tumor regression in triple negative breast cancer humanized mice was demonstrated for the capped tribody, which was superior to the uncapped tribody. No effect was shown with the non-cleavable capped tribody whose CD3 binding function is irreversibly blocked. Cytotoxic effect and binding to CD3 was fully recovered following capping cleavage. PBMC-mediated cytotoxicity against 5T4+ cancer cells was demonstrated at picomolar EC50 while no effect was observed in 5T4- cancer cells. IM1240 and non-capped tribody inhibited NKG2A-HLA-E interaction in a dose-dependent manner, while NKG2A mutated tribody had no effect. NK cell mediated cytotoxicity against HLA-E expressing cancer cells was demonstrated, while NKG2A mutated tribody had no effect. A cytokine release assay from hPBMC showed a 5T4+ cancer cell dependency and was inhibited by the cap, showing superior safety profile. Plug and Play abilities of the platform were demonstrated through different tribodies targeting 5T4, EGFR and NKG2D which demonstrated low nM and selective binding to cells overexpressing the target, and efficient PBMC and NK mediated cytotoxicity.
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