IM1240 is a conditionally activated, capped-CD3 × 5T4 × NKG2A tri-specific designed to direct tumor-selective T-cell activation while also leveraging NKG2A-mediated checkpoint inhibition to enhance anti-tumor activity.
The new data, generated in the laboratory of Dr. Amir Horowitz of the Tisch Cancer Institute and the Lipschultz Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, demonstrated potent anti-tumor activity for IM1240 across multiple treatment-resistant patient-derived tumor samples. All seven tested samples responded to IM1240 treatment, including samples from PD-1 or PD-1/chemo-resistant head and neck squamous cell carcinoma metastatic lymph nodes and enfortumab vedotin + PD-1-resistant muscle-invasive bladder cancer.
"These data demonstrate the critical contribution of IM1240's NKG2A arm, confirmed using a variant with a mutated NKG2A-binding domain, which resulted in loss of apoptotic activity across all samples," said Dr. Horowitz. "Further tissue profiling analyses of NSCLC patient-derived explants demonstrated that treatment with IM1240 induced pronounced immune cell reorganization within the tissue hallmarked by visible induction of mature tertiary lymphoid structures (TLS), which are associated with strong anti-tumor immunity and improved clinical outcomes, as well as increased abundances of CD8 T cells and NK cells, and reduction in numbers of Tregs and tumor cells."
Gil Efron, Chief Executive Officer of Purple Biotech added, "The differentiation of the CAPTN-3 platform from other T cell engagers with the contribution of its NKG2A arm that dually engages NK cells and enhances activity and expands the therapeutic index which we believe is very important for patients' treatment and for potential improved clinical outcomes, and we are excited by these results from the lab of Dr. Amir Horowitz. IM1240 has the potential to treat resistant patients across multiple tumor types as supported by preclinical data in triple-negative breast cancer, NSCLC, head & neck and bladder cancer models, suggesting a significant market opportunity."