We here investigate the therapeutic efficacy of NTX-301...a novel HMA in venetoclax-resistant and TP53-mutant AML. Importantly, using a PDX model developed from an AML patient who relapsed from venetoclax/HMA, NTX-301 alone demonstrated great anti-leukemia activity and significantly extended survival (167 vs 114 days of control, P=0.0001), while venetoclax or venetoclax/5-Aza did not....our data suggest that NTX-301 has more potent anti-leukemia activities compared to current HMA in clinic and synergizes with venetoclax in venetoclax-resistance and TP53-mutant AML...