Constellation Pharmaceuticals Initiates Clinical Development of CPI-1205, a Novel Inhibitor of EZH2, in Patients with Lymphoma

Second Constellation Pipeline Program to Enter the Clinic

CAMBRIDGE, Mass. –April 28, 2015 – Constellation Pharmaceuticals, Inc., a leading biopharmaceutical company in the field of chromatin biology, today announced that it has initiated a Phase 1 clinical trial of CPI-1205, a novel inhibitor of EZH2, in patients with previously treated and progressive lymphomas. This first-in-human trial is currently open at Horizon Oncology in Lafayette, Indiana, Sarah Cannon Research Institute in Nashville, Tennessee, the John Theurer Cancer Center in Hackensack, New Jersey and the Massachusetts General Hospital in Boston, Massachusetts.

“We are excited to advance CPI-1205 into the clinic to explore the therapeutic potential of EZH2 inhibition in patients with lymphoma and other malignancies,” said Patrick Trojer, Ph.D., the lead biologist for Constellation’s histone methyltransferase program. “Our interest is in targeting chromatin regulatory pathways in order to interfere with aberrant transcriptional programs in cancer. CPI-1205 allows us to target a pathway that cancer cells utilize to silence certain genes and thereby gain a growth advantage. Our preclinical data and that of other investigators suggest that EZH2 inhibition may have broad activity in lymphoma as well as activity in solid tumors. CPI-1205 has a number of favorable attributes that make us optimistic that its preclinical activity will translate into anti-tumor activity for patients.”

About EZH2

Enhancer of Zeste Homolog 2 (EZH2) is part of a multi-protein complex called the polycomb repressive complex 2 (PRC2). The function of the PRC2 complex is to selectively suppress gene expression. As part of the PRC2 complex, EZH2 catalyzes the transfer of methyl groups to a distinct lysine residue of a histone protein (H3) that is associated with DNA. The methylation of this lysine residue reduces expression of the associated gene. EZH2 is recurrently mutated in diffuse large B cell and follicular lymphomas and is frequently overexpressed in many other malignancies. Small molecule inhibitors of EZH2’s enzymatic activity have been shown to selectively alter gene expression in a way that leads to cancer cell death. Targeting EZH2’s enzymatic activity is therefore a promising approach for the treatment of cancer.

About Lymphoma

Lymphoma is a type of blood cancer that develops in the lymphatic system, typically in lymph nodes, the spleen and bone marrow. It occurs when a lymphocyte – a type of white blood cell that helps protect against disease and infection – undergoes a malignant change and multiplies. The lymphoma cells eventually become so numerous that they cause enlargement of lymph nodes, of the spleen, and can interfere with ability of the bone marrow to produce normal blood cells. About 54 percent of the hematologic malignancies (“blood cancers”) that occur each year are various types of lymphoma[1]. Some lymphomas, like Hodgkin lymphoma, are now frequently cured with standard treatments, and for many lymphomas effective but non-curative treatments are available. Unfortunately, many lymphomas still eventually progress in spite of standard treatment, and hence there remains a need for new therapies.

About Constellation Pharmaceuticals

Constellation Pharmaceuticals leverages insights from the rapidly expanding field of chromatin biology to discover and develop small molecule therapeutics for the treatment of cancer, inflammatory/immunologic disorders and other diseases. In addition to the recent progression of its EZH2 inhibitor, CPI-1205, into the clinic, Constellation is also evaluating a BET protein bromodomain inhibitor, CPI-0610, in three Phase 1 clinical trials in the U.S. The company’s innovative product discovery engine targets both enzymes that modify the dynamic structure of chromatin (writers and erasers) and other proteins that interact with chromatin (readers) to control gene expression. Restoration of normal gene expression through chromatin modulation by highly selective and specific inhibitors promises to be a powerful approach to the development of important new medicines against a broad range of diseases. For more information, please visit the company’s website at constpharma.wpengine.com.

[1] The Leukemia & Lymphoma Society