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news.Tekmira Pharmaceuticals has secured licenses from Alnylam Pharmaceuticals under its InterfeRx program to develop a new RNAi therapeutic targeting two validated oncology targets - WEE1 and CSN5.
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Gene expression data from human tumor samples indicate that both CSN5 and WEE1 genes promote tumor cell growth and cancer pathogenesis.
WEE1 is a tyrosine kinase that regulates cell cycle progression and the response to DNA damage by its control of a cell cycle checkpoint that precedes entry into cell division.
Inhibiting WEE1 increases cancer cell sensitivity to DNA damaging agents and other therapies.
CSN5 is the catalytic center of the COP9 signalosome, a multi-protein complex involved in regulating protein degradation via the ubiquitin proteasome pathway. CSN5 regulates protein turnover and other protein interactions that affect many stages of tumorigenesis.
Silencing of CSN5 causes molecular changes that inhibit tumor cell growth and increases apoptosis (programmed cell death).
Lipid nanoparticle (LNP) delivery of siRNA targeting WEE1 effectively suppresses tumor growth and increases the survival of treated animals in preclinical models of human hepatocellular carcinoma (HCC or liver cancer) in a dose-dependent manner.
LNP delivery of siRNA against CSN5 resulted in 80% inhibition of tumor cell growth in vitro and significant reduction in tumor growth in preclinical models of human liver cancer.
A combination RNAi approach that depletes both WEE1 and CSN5 may be ideal for inactivating multiple pathways that promote cancer, and to avoid cellular resistance.
Combinations of WEE1 and CSN5 siRNA resulted in a significant increase in apoptosis in human liver cancer cells in vitro, relative to the action of each siRNA alone.
Tekmira is conducting additional preclinical work on a WEE1/CSN5 product candidate including the evaluation of a number of tumor specific LNP formulations prior to initiating formal toxicology studies required for filing an Investigational New Drug application.
Tekmira has access to eight InterfeRx licenses at pre-negotiated financial terms and has identified the first five targets, including ApoB, PLK1, Ebola, WEE1 and CSN5.