On April 19, 2023 Purple Biotech Ltd. ("Purple Biotech", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies that harness the power of the tumor microenvironment (TME) to overcome tumor immune evasion and drug resistance, reported new results presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando (Press release, Purple Biotech, APR 19, 2023, View Source [SID1234630312]). 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 (ICB) therapies. The study was led by researchers at The University of Texas MD Anderson Cancer Center. Main results are as follows:

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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.

"These results suggest that combining ICB with NT219 may be a promising strategy to reprogram the immune profile of the TME to enhance anti-tumor immunity, turning ‘cold’ tumors ‘hot’ and re-sensitizing resistant tumors to anti-PD1 therapy", said Hadas Reuveni, PhD, VP R&D at Purple Biotech. "The insidious process by which tumors become resistant to so many of our most promising cancer drugs robs patients of hope and of time with their families. Lengthening the duration of treatment as well as broadening the patient population that may benefit from these treatments address the highest obstacles of ICB therapies today."

Results from 5073/7 "NT219 induces tumor PD-L1 expression and potentiates anti-PD-1 efficacy" presented as a poster on April 18, 2023, at the AACR (Free AACR Whitepaper) 2023 Annual Meeting.

The full poster can be viewed on the Purple Biotech Website at View Source

About NT219

NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. In a Phase 1/2 study of NT219, the Company is currently advancing it as a monotherapy treatment of solid tumors, and in a dose escalation in combination with cetuximab for the treatment of recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) or colorectal adenocarcinoma (CRC). These studies will be followed by an expansion phase of NT219 at its recommended Phase 2 level in combination with cetuximab in patients with recurrent and metastatic SCCHN.