Purple Biotech presents preclinical data on CAPTN-3 antibody platform

Purple Biotech (PPBT) announced the presentation of new preclinical data on its novel CAPTN-3 tri-specific antibody platform in a poster presentation at the 2025 Annual Congress of the European Association for Cancer Research, that was held in Lisbon, Portugal from June 16-19, 2025. The design of the CAPTN-3 lead product and other candidates in this platform includes an anti-NKG2A arm, which acts both as an NK cell antigen and as an immune checkpoint on both T cells and NK cells through its interaction with HLA-E, which is often upregulated in tumors to evade immune detection. NKG2A expression identifies a subset of human gamma delta 2 T cells exerting the highest antitumor effector functions. Anti-NKG2A function is required to unleash the NKG2A+ gamma delta 2 T cell anti-cancer activity. Our data demonstrate that the NKG2A arm in CAPTN-3 TCE synergizes with the anti-CD3 arm to induce significant cytotoxic effects against solid tumor cells. NKG2A is an immune checkpoint that plays an important role in the exhaustion of cytotoxic T cells in the tumor microenvironment. The preclinical data demonstrate the potential of CAPTN-3 to re-invigorate exhausted T cells and efficiently kill solid tumor cells, largely attributed to the significant contribution of the unique anti-NKG2A arm. These activities are further supported by the in-vivo data demonstrating that both the NKG2A and CD3 arms contribute to the sustained tumor regression observed in mice models. These results underscore the innovative design of CAPTN-3, highlighting the impact of the novel anti-NKG2A arm and its synergistic effect with the anti-CD3 arm. The CAPTN-3 platform creates a tri-specific scaffold with three binding arms. In the variable region, one arm conditionally binds to CD3, only after the cap has been cleaved by proteases in the TME. The other variable region engages natural killer cells, activating the innate immune system to join activated T cells in the killing of tumor cells. The constant region of the tri-specific antibody targets tumor associated antigens to recruit both NK and T cells to the tumor. Through activation of both the innate and adaptive immune systems, the CAPTN-3 platform can generate synergistic responses within the TME, without the risk of off-target cytokine release. Key Highlights from the Poster Presentation: The lead CAPTN-3 tribody, IM1240, induced sustained tumor regression in a triple negative breast cancer xenograft model. The ‘capped’ CD3 arm remained inactive in serum samples of advanced cancer patients and healthy donors and is selectively unmasked by TME proteases, expanding the therapeutic window and reducing potential systemic NKG2A+NK cell depletion. IM1240’s NKG2A checkpoint blockade arm synergizes with the CD3 engager to activate both innate and adaptive immune subsets, translating to potent cytotoxicity in vitro and in vivo. The poster demonstrates: Activation of the extremely high antitumor NKG2A+ gamma delta 2 T effector cells; Reinvigoration of exhausted T cells against solid tumor cells; The added value of IM1240 NKG2A arm to the in-vivo tumor suppression. Additional CAPTN-3 tribodies, such as IM1060 and IM1065, demonstrated significant tumor regression, underscoring the platform’s modularity and customizable capabilities. Superior efficacy versus combination of individual antibodies was demonstrated.