Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, announced that the Company has dosed the first patient in a Phase 1/2 clinical trial of CPI-0209.
CPI-0209 is a second-generation EZH2 inhibitor that has been designed to achieve comprehensive target coverage through extended on-target residence time and enhanced potency compared with first-generation EZH2 inhibitors. These features lead to faster onset of action than first-generation EZH2 inhibitors as well as robust anti-tumor activity in models of multiple cancer types.
“We recognized that a best-in-class molecule with enhanced potency and residence time may help to access the full potential of EZH2 inhibition in cancer,” said Dr. Patrick Trojer, Chief Scientific Officer. “We believe that CPI-0209 can deliver on this need, and we are eager to learn more about CPI-0209 in the clinic. We have seen impressive pre-clinical activity of CPI-0209 and are excited to take the first steps toward bringing CPI-0209 to patients.”
Constellation has utilized its epigenetics platform, including expertise in translational science, to identify novel, targeted patient contexts that may be responsive to inhibition by next-generation EZH2 inhibitors. For instance, in xenografts derived from bladder cell lines harboring ARID1A mutations, once-daily treatment with CPI-0209 achieved regression at well-tolerated doses – activity that was superior to that from the chemotherapeutic agent cisplatin, a standard of care in bladder cancer. At the American Association for Cancer Research Bladder Cancer meeting on May 19, 2019, Constellation presented a poster with supporting data from these studies.
The Phase 1 dose escalation phase of the clinical trial will study CPI-0209 monotherapy in advanced, relapsed solid tumor patients. After determining the recommended Phase 2 dose (RP2D) for the monotherapy, we will pursue expansion arms in selected tumor indications as well as combination therapy development, employing a biomarker strategy that includes assessment of ARID1A.
About Constellation Pharmaceuticals
Constellation Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel therapeutics that selectively modulate gene expression to address serious unmet medical needs in patients with cancer. The Company has a deep understanding of how epigenetic and chromatin modifications in cancer cells and in the tumor and immune microenvironment play a fundamental role in driving disease progression and drug resistance. Constellation is driving development of the EZH2 inhibitors CPI-1205 and CPI-0209 for the treatment of metastatic castration-resistant prostate cancer and other cancers as well as the BET inhibitor CPI-0610 for the treatment of myelofibrosis. The Company is also applying its broad research and development capabilities to explore other novel targets that directly and indirectly impact gene expression to fuel a sustainable pipeline of innovative small-molecule product candidates.