When Xconomy last checked in on Cambridge, MA, epigenetics startup Constellation Pharmaceuticals, in the fall of 2009, CEO Mark Goldsmith declined to disclose details about the company’s pipeline. These days, he’s willing to be a little more forthcoming. On June 6, during the American Society of Clinical Oncology meeting in Chicago, Constellation announced it had added $15 million to its Series B venture financing—bringing the total amount of money raised to an impressive $70 million.
And now the nascent world of epigenetics is getting a glimpse of how Constellation’s strategy and pipeline are evolving. In an interview a few days after the funding announcement, Goldsmith explained to Xconomy that Constellation is focusing on three different classes of drug targets, and he used terminology developed by Rockefeller University epigenetics researcher David Allis to describe them: “writers,” “erasers,” and “readers.”
In general terms, epigenetics is the study of molecular changes in cells that can activate or de-activate genes without affecting the underlying DNA code. Multiple enzymes—those writers, erasers, and readers that Constellation is targeting—are believed to play a role in epigenetic changes that may promote many diseases, including cancer, which is Constellation’s main focus.
Although the science of these enzymes is still not completely understood, they are all factors that modulate chromatin—the combination of DNA and the proteins that the DNA is wound around in the cell’s nucleus—as a means of turning genes on and off, Goldsmith says. “We think there are drug targets in each of these classes.”
One of Constellation’s lead programs targets a member of the writer class called EZH2, Goldsmith says. “We are quite interested in this as a cancer target because it is commonly over-expressed in many types of tumors,” Goldsmith says. “It also harbors a specific set of mutations that are thought to contribute to the development of some lymphomas.”
But Constellation is far from alone in its pursuit of EZH2. Another hot Cambridge-based epigenetics startup, Epizyme, is also pursuing the enzyme. Epizyme has raised $54 million in venture capital and scored development deals with GlaxoSmithKline (NYSE: GSK) and Eisai Pharmaceuticals. Epizyme and Eisai are now partnered on a program that aims to develop a drug for patients with EZH2-mutant non-Hodgkin’s lymphoma.
Goldsmith acknowledges some overlap between Constellation and Epizyme, but he’s quick to assert that his company is taking a broader approach to epigenetics. “We are deeply involved in studying all three classes,” he says. “You can’t think about writers without understanding erasers and readers. We are a chromatin-biology based company. We think it will be more powerful to take a holistic view of chromatin.”
All of Constellation’s previous investors participated in the recent funding, including Third Rock Ventures, The Column Group, Venrock Associations, SR One, and Altitude Life Science Ventures.
Goldsmith, who was handed the CEO reigns in 2009 by Third Rock partner Mark Levin, says Constellation will disclose more drug targets later this year. With the funding, he says, “we’ve made dramatic progress. We spent our first two years establishing our platform. Now we can focus on developing a portfolio of products.”
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