Silmitasertib, also known as CX-4945, was originally developed by Cylene Pharmaceuticals, a San Diego-based biotech that ceased operations in 2013.
Since then, Senhwa Biosciences, which is headquartered in Taiwan but also has a San Diego base gained the rights to the small molecule, first in class, casein kinase 2 (CK2) inhibitor.
CK2 is overexpressed in a number of tumors. Various studies have shown silmitasertib appears to have good anticancer activity. For example, it triggers autophagy and promote apoptosis of cancer cells in pancreatic and lung cancer and also promotes colorectal cancer cell death.
Senhwa is currently testing silmitasertib in early human trials for treatment of cholangiocarcinoma, basal cell carcinoma, medulloblastoma and neuroblastoma.
In preclinical studies, the small molecule showed good oral bioavailability and was able to effectively inhibit tumor growth in animal studies while being well tolerated.
When combined with DNA-damaging chemotherapy drugs such as gemcitabine and cisplatin, the anticancer activity of silmitasertib seems to be enhanced so it is being tested as an add-on therapy in the new trial.
The phase 1/2 study will include 114 children and young adults with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma in the US.
"We are thrilled to be able to move this important research forward on a larger scale," said Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, which is supporting the study.
“The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally.”
Additional indication for Covid-19 patients
As well as being a promising anti-cancer therapy, silmitasertib is being tested to treat people infected with SARS-CoV-2 who develop serious symptoms that require hospitalization in a phase 2 study.
CK2 is involved in regulating signaling pathways important for innate immune responses. Inhibiting this protein kinase can help reduce the excessive cytokine storm immune response often seen in people with severe Covid-19.
Studies have shown that silmitasertib and other kinase inhibitors seem to reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, both of which are high in hospitalized Covid-19 patients.
So far results phase 2 results announced by Senhwa have been good with significantly better recovery times observed for Covid-19 patients given silmitasertib versus standard care, with a good safety profile.
