A targeted approach for treating hematological cancers and beyond

Kurome Therapeutics is a preclinical stage company that is developing a series of IRAK1/4, panFLT3 inhibitors. Preclinical studies in the Starczynowski lab have demonstrated:

  • Broad range of efficacy in MDS and AML patient-derived cell lines
  • Synergy with Venclexta® (Venetoclax) to improve Venclexta® potency
  • Identification of a biomarker that correlates with prognosis in AML patients and maximal activation of immune signaling through this pathway in AML cells
  • Increased overall survival in cell line and patient-derived xenograft models, well beyond that of existing FLT3 inhibitors
  • Maintenance of complete efficacy even in settings of adaptive resistance to FLT3 inhibitors and in settings of FLT3 mutations

The IRAK1/4 signaling complex lies at a critical signaling node that drives cancer cell survival through multiple mechanisms

  • The IRAK1/4 complex lies at a critical signaling node that is downstream of several innate immune-signaling pathways that are dysregulated in cancer cells
  • Over-activation of this pathway in cancer cells acts as an oncogene-like driver that mediates cancer cell growth and/or survival
  • This signaling node is also a key molecular hub for modulation of stress response pathways following cancer therapies that mediate resistance and contribute to relapse
  • Inhibition of the IRAK1/4 signaling complex subverts cancer’s ability to mount the stress response, and ablates the dependency of the cancer cell on the over-activated immune signaling pathways
Therapy mediated versus Genetic mediated IRAK 1/4 Activation.

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