Non-small cell lung cancer Pancreatic cancer, etc.
Background of Development
IRAK-M (interleukin 1 receptor associated kinase 3) is a known negative regulator of the MyD88-dependent TLR/IL1R pathway and is specifically expressed in myeloid cells to suppress excessive activation of innate immunity. Cancer growth suppression has been reported in an in vivo syngeneic model using IRAK-M knockout mice1), and IRAK-M is considered to be a very attractive target for cancer immunity through its mechanism of action that releases immunosuppression in myeloid cells involved in immunosuppression. In non-small cell lung cancer and pancreatic cancer, IRAK-M expression levels have been reported to correlate with patient prognosis1) 2).
On the other hand, because IRAK-M is a pseudokinase that lacks enzymatic activity, it has been classified as an “Undruggable Target” and inhibiting its function with conventional low molecular weight compounds has been difficult. Against this background, we believe that the targeted protein degradation is the optimal modality for drug discovery targeting IRAK-M.
1) Oncogene. 2011 May 26; 30(21): 2475–2484.
2) Dig Dis Sci. 2014 Nov;59(11):2714-20.
Developed Compound FIM-001
By applying our targeted protein degrader discovery platform RaPPIDS™, we succeeded in finding a drug candidate FIM-001 in a short period of time. FIM-001 exhibits activity to induce cancer immunity and has shown anti-tumor effects in animal models known to be non-responsive to checkpoint inhibitors, which have been the mainstream of cancer immunotherapy in recent years. Safety studies are currently underway for clinical trials.