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NTX-301 Reprograms Epigenetics to Fight Treatment-Resistant AML

Preclinical results link selective DNA methylation changes to Hippo pathway activation and reduced YAP activity, which investigators say justifies clinical testing.

Overview

  • MD Anderson researchers reported in Clinical Cancer Research that NTX-301 outperformed the standard hypomethylating agent azacitidine in cell lines and patient-derived xenograft models.
  • The study, published July 13, 2026, found NTX-301 remained active in leukemias that had acquired resistance to hypomethylating therapy and to venetoclax.
  • NTX-301 selectively reprogrammed DNA methylation to increase expression of Hippo pathway genes and lower YAP activity, a change linked to reduced cancer cell survival.
  • Combining NTX-301 with venetoclax produced stronger anti-leukemia effects than either drug alone and reduced both leukemia blasts and stem or progenitor cells in resistant samples.
  • The findings are preclinical; the work was supported in part by Pinotbio and MD Anderson funds and the authors recommend further studies and clinical trials to test safety and patient benefit.