Constellation Pharmaceuticals Announces Initiation of Phase 1b/2 Study of CPI-1205

Demonstrates the company’s ability to utilize its platform to identify mechanisms of epigenetics-mediated drug resistance to cancer immunotherapies

Trial to evaluate the potential for the company’s most advanced small-molecule EZH2 inhibitor to be used in combination with Yervoy® and other immunotherapies 

CAMBRIDGE, Massachusetts, January 16, 2018 – Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research and development in cancer epigenetics, today announced it has initiated a Phase 1b/2 clinical trial to evaluate CPI-1205, a small-molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2), combined with checkpoint inhibitor ipilimumab (marketed as YERVOY® by Bristol-Myers Squibb) and potentially other cancer immunotherapies. The study, named ORIOn-E, is based on translational insights which identified combination approaches using epigenetics-mediated mechanisms aimed at Overcoming Resistance to Immune Oncology therapies by inhibiting EZH2.

“This is the second combination study we’ve initiated evaluating the potential for CPI-1205 to overcome resistance mechanisms to existing cancer therapies,” said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. “Our preclinical results with CPI-1205 demonstrate that epigenetic targets can be utilized by cancers to suppress the immune system and render immunotherapy treatment options less effective. We aim to build on this insight with CPI-1205 in clinical trials and with other epigenetic therapies that we discover and develop in this important area of research.”

CPI-1205 is a potent, highly selective, first-generation small-molecule inhibitor of an enzyme called EZH2. In pre-clinical studies, CPI-1205 has shown potential to re-wire T regulatory and T effector cells within tumors to enhance tumor rejection alone and synergistically in combination with immune checkpoint inhibition.

“Since they were first made available in the U.S., checkpoint inhibitor therapies like ipilimumab have provided considerable benefit for patients with many different cancers. However, many patients do not respond to therapy or relapse after initial response,” said Adrian Senderowicz, M.D., senior vice president and chief medical officer of Constellation Pharmaceuticals. “CPI-1205 plays a critical role in inhibiting the suppressive function of regulatory T cells and consequently may address resistance mechanisms that limit the benefit of immune checkpoint inhibitors in patients.”

The Phase 1b portion is a dose escalation study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and the assessment of potential predictive biomarkers in patients across solid tumors when treated with CPI-1205 in combination with ipilimumab. The Phase 2 portion will be conducted in melanoma patients, among other cancers.

About CPI-1205
CPI-1205 is a therapeutic candidate from Constellation Pharmaceuticals’ EZH2 portfolio and is an inhibitor of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several pro-cancer pathways that contribute to drug resistance.

About Constellation Pharmaceuticals
Constellation Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel small-molecule therapies based on its pioneering research in cancer epigenetics. With a decade of experience in the field, the company has an unparalleled understanding of how epigenetic regulators modulate gene expression in cancer cells and in the tumor and immune microenvironment. Constellation is translating these insights to advance the company’s two lead clinical programs, CPI-1205 and CPI-0610, and in novel targets for which cancer epigenetics may help overcome resistance mechanisms to currently available treatment options.

For more information, please visit www.constellationpharma.com.

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