Purple Biotech reports preclinical data on NT219 at AACR meeting

Purple Biotech shared new results presented at the American Association for Cancer Research Annual Meeting 2023 in Orlando. The results demonstrate the potential of NT219, the Company’s novel small molecule dual inhibitor of IRS1/2 and STAT3 escape mechanisms, to work synergistically with either anti-PD1 or anti-CTLA4 drugs to reprogram the immune profile in the TME and convert resistant tumors to responders to Immune Checkpoint Blockage therapies. The study was led by researchers at The University of Texas MD Anderson Cancer Center. Main results are as follows: NT219 induced significant PDL1 expression in melanoma cells in-vitro and showed a synergistic effect with anti-PD1 therapy in tumor growth inhibition in-vivo. The induction of PDL1 by NT219 was much higher in the ICB-resistant melanoma strain as compared to ICB-sensitive cells, suggesting the potential to re-sensitize refractory tumors to anti-PD1 therapy. Treatment of immunocompetent mice bearing ICB-resistant tumors with NT219 in combination with either anti-PD1 or anti-CTLA4 therapies showed a significant increase in activated CD8 cytotoxic T cells and NK cells in the TME; this effect was seen in parallel with a significant decrease in the infiltration of immunosuppressive populations, including regulatory T cells, and myeloid-derived suppressor cells, and M2 macrophages. No such effects were detected with either therapy alone. Similarly, NT219 in combination with anti-PD1 showed synergistic effects inducing significant tumor growth inhibition of ICB-resistant tumors, while each therapy alone had no effect. The ICB-resistant clone showed higher levels of both IRS1 and STAT3 activation in comparison with the ICB-sensitive clone of the same origin melanoma cells. Treatment with NT219 diminished both IRS1 and STAT3 phosphorylation in both cloned cell lines and showed a durable effect on these target proteins, which are known to be involved in drug resistance.