HC-7366
HC-7366
HC-7366
Clinical Development of HC-7366
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HC-7366 is under investigation in a Phase 1b trial as monotherapy and in combination with a HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma (ccRCC). HC-7366 is also under investigation in a Phase 1b study as monotherapy and in combination with venetoclax and azacitidine for the treatment of acute myeloid leukemia (AML).
GCN2 and the Integrated Stress Response
- GCN2 (General Controlled Nonderepressible 2), one of the kinases in the integrated stress response (ISR) family, responds to amino acid deprivation and is a key metabolic stress sensor in cells
- While cancer cells are known to utilize the ISR for survival, prolonged or hyper activation of the ISR has been shown to induce an anti-tumor response
- Hyperactivation of the ISR via GCN2 is shown to result in anti-tumor activity
- Activated GCN2 phosphorylates eIF2⍺, inhibits global translation but enhances ATF4 translation resulting in either a pro-tumor survival or anti-tumor response in a context-dependent manner
- GCN2 also plays a role in the tumor immune microenvironment
- Activation of GCN2 by HC-7366 results in a broad, lethal anti-tumor stress response; pre-clinical activity has been demonstrated in several tumor histologies
- HC-7366 is now being studied in the clinic in R/R ccRCC and AML and FDA Fast Track Designation has been granted in AML