With more and more unknown field of cancer has been unveiled, the mechanism to inhibit DNA damage response (DDR) of cancer cell is the trend of anticancer drug development nowadays. DDR is hot and new drugs designed with DDR mechanism such as PARP inhibitors are stars and bringing huge business opportunities behind. According to the preclinical study have shown that Senhwa CX-5461 can effectively inhibit the growth of tumor cells that have already developed resistance to DDR drugs, which of market value estimated of US$ 20 billion globally. CX-5461 aims to become the rescue medication of DDR drugs, in other words, the next generation DDR therapeutic for the cancer treatment.
At present, when it comes to targeted drugs, PARP inhibitors are the leading players. The main mechanism is to inhibit the activity of PARP protein and block the DNA repair of cancer cells. Currently three PARPi drugs have been approved by US FDA and many other PARP inhibitors are in the clinical stage. DDR drugs are regarded as cancer savior and the stock prices of the companies that develop the drugs have dramatically gone up. For example, Tesaro once soared five times of its share price from US$ 35 to US$ 190 per share in a year with a market cap of US$ 7.8 billion.
However, according to clinical data, Lynparza®, the first PARP inhibitor approved in 2014 and patients have gradually developed drug resistance. CX-5461, by applying mechanism different from PARP inhibitors, can reduce the generation of drug resistance and delay the relapse. CX-5461 is designed to stabilize DNA G-quadruplexes (G-4) of cancer cell and lead to replication fork stalling. While acting in concert with HR pathway deficiency, such as BRCA1/2 mutations, which stalls replication forks undergo DNA breaks and causes cancer cell death.
CX-5461 in combination with HRD tumors may be exploited through a synthetic lethality approach targeting DNA repair defects in HRD tumors. Senhwa is the first biotech company applying G-4 mechanism in the clinical stage.
Due to the rapid growth of cancer population, the competition in anticancer drug development industry is fierce. Even big pharmaceutical or biotech companies may face the failure of drug development after investing vast amount of time and money. CX-5461 is the first-in-class new drug with the potential to become rescue medication for PARP inhibitor-resistant patients, which is the next generation DDR drugs for cancer treatment.