More than two years after Genentech passed over its option to acquire Constellation Pharmaceuticals, the immuno-oncology company raised $100 million that will bankroll a cancer epigenetics candidate through clinical trials, as well as advance several pipeline prospects.
Its work is based on epigenetics, the changes in gene function that don’t involve changes in the actual DNA. For example, DNA methylation—the binding of methyl groups on top of DNA—and histone modification both affect gene expression. By regulating the proteins and enzymes involved in such modifications, Constellation is looking to “tune up” or “tune down” genes that may be responsible for certain disease states, said CEO Jigar Raythatha in an interview.
The funding will support clinical work for CPI-1205, a small molecule that increases the expression of genes that are abnormally suppressed in some cancers. It works by blocking the enzyme EZH2 and is currently in a phase 1 dosing trial as a combination with the androgen inhibitors Xtandi and Zytiga in metastatic castration-resistant prostate cancer. It is also in studies in patients with solid tumors and blood cancers.
The capital came from a wide range of investors, including new investors Cormorant, Deerfield, OrbiMed and Sirona, as well as existing backers, such as Venrock, Third Rock Ventures and The Column Group, according to a statement.
“This financing gives us additional flexibility and runway to pursue the clinical development of CPI-1205 and CPI-0610, our lead product candidates, as well as advance other novel molecules from our cancer epigenetics platform into development,” Raythatha said in the statement.
CPI-0610 is in clinical studies as a treatment for myelofibrosis as both a monotherapy and in combination with a JAK inhibitor. The company also has a second-generation EZH2 program in the works as well as a number of programs in “various stages of discovery.” Raythatha did not specify which indications those are targeting.
Back in January 2012, Constellation and Genentech inked a three-year deal that saw the latter commit $95 million to the former’s R&D overhead and with an option to buy the company. But the partnership ended with no buyout in 2015, and Constellation quietly laid off 23 staffers as part of its plan to go it alone. It went on to score $55 million at the end of the year.
In March 2017, Raythatha, who had previously led corporate development at Constellation, returned to take the reins as CEO. He had departed in 2013 to serve as chief business officer at Jounce Therapeutics, which pulled off an upsized $140 million IPO in January 2017.
Asked what brought him back to Constellation, Raythatha said it was the science: “I had grown up with it from inception. […] I really loved the science and the opportunity to return was really attractive. When I looked at the pipeline, I think it’s very rare to find a company with as broad, robust and deep a pipeline as Constellation had.”