On March 14, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported preclinical proof of concept data for its conditionally-activated tri-specific antibody platform (Press release, Purple Biotech, MAR 14, 2024, View Source [SID1234641171]).
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"Our tribody platform is differentiated with its dual engagers including its NK cell engager having a dual mechanism of action, in addition to the conditionally activated T cell engager. We are excited about the potential of this platform to produce a pipeline of promising drug candidates that can be effective across numerous solid cancer tumors," stated Gil Efron, Chief Executive Officer of Purple Biotech.
Prof. Amir Horowitz, Assistant Professor of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, commented, "Purple Biotech’s tribody platform, apart from being a NK cell engager, via the anti-NKG2A arm, also functions as an important immune checkpoint inhibitor of both NK cells and specific subsets of T cells, unleashing both innate and adaptive immune systems against the tumor. This conditionally-activated platform requires a complex model for optimal and translational analysis, hence patient-derived explant (PDE) models were selected to demonstrate the added value of the anti-NKG2A modality."
Using 5T4-expressing lung cancer PDE model, where the immune cells and the tumor cells are derived from the same patient (autologous model), the studies showed a synergistic effect of the T cell engager and NK cell engager arms. While each bispecific agent, 5T4xCD3 or 5T4xNKG2A, showed only low response, the tribody platform’s leading candidate IM1240 (5T4xCD3xNKG2A) having both engagers in one product, demonstrated a synergistic strong anti-tumor response. This effect is activated through the presence of 5T4 positive tumor cells. The advantage of the 5T4 arm was also validated using in-vitro PBMC-mediated cytotoxicity of cancer cell line studies which demonstrated 5T4-specific effect. While cytotoxicity at pM range was observed in 5T4-positive lung and breast cancer cells, no effect was observed against 5T4-negative cancer cells.
Purple Biotech’s cleavable capping technology confines the compound’s therapeutic activity to the local tumor micro environment (TME), which increases the anticipated therapeutic window in patients. This cap is attached to the anti-CD3 moiety and blocks its interaction with circulating CD3 positive T cells, thereby impeding potential off-tumor adverse reactions and also improving PK properties. The cap is designed to be cleaved off by multiple TME-specific proteases, which increase the likelihood for cleavage by many tumor types. Upon removal of this cap, the anti-CD3 moiety of the molecule is freed to bind and activate T lymphocytes against the tumor via CD3.