Purple Biotech reports preclinical proof of concept for tribody platform tech

Purple Biotech reported preclinical proof of concept data for its conditionally-activated tri-specific antibody platform. Using 5T4-expressing lung cancer PDE model, where the immune cells and the tumor cells are derived from the same patient, 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 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, 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.