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NT219

Overview and Mechanism of Action

NT219 is a first-in-class, novel small molecule targeting both IRS1/2 and STAT3, important oncogenic drivers and major drug resistance pathways in many hard-to-treat cancers. In preclinical studies, NT219 demonstrated strong efficacy in preventing acquired resistance and reversing tumor resistance when administered as a monotherapy and in combination with various existing oncology therapies.

IRS1/2

  • Scaffold proteins, mediating mitogenic, metastatic, angiogenic and anti-apoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumors
  • Regulates major survival pathways such as the PI3K/AKT, MEK/ERK and WNT/β-catenin
  • Activated as a feedback response to anti-cancer therapies
  • IRS plays an important role in promoting a tumor-protective microenvironment, by mediating upregulation of TAMs and CAFs

STAT3

  • Well-established transcription factor associated with the tumorigenic phenotype
  • STAT3 is broadly hyperactivated in many cancers, promoting proliferation, survival, angiogenesis and metastasis
  • STAT3 pathway is required for TGFβ-induced EMT and cancer cell migration and invasion
  • STAT3 is a critical player in tumor immune evasion, suppressing immune stimulators and enhancing immunosuppressive factors

Clinical Studies

We are concluding a phase 1 dose escalation study of NT219 as a single agent in patients with solid tumors and a dose escalation phase of NT219 in combination with cetuximab, for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck cancer and colorectal adenocarcinoma.  In February 2024, we determined the RP2D for NT219 to be 100 mg/kg.

We are currently planning the phase 2 study of NT219 at its RP2D level in combination with cetuximab for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck in the first half of 2024.

 

NT219 - References (Download)
ClinicalTrials.gov NCT04474470 - A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
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