Constellation Pharmaceuticals Presents Phase 1 Data for CPI-0209 at ASCO Annual Meeting

  • Pharmacodynamic data show comprehensive target engagement after treatment with CPI-0209 monotherapy
  • Oral, once-daily 350mg dose selected for Phase 2
  • Enrollment of tumor-specific expansion cohorts is ongoing

CAMBRIDGE, Mass., June 04, 2021 (GLOBE NEWSWIRE) -- Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today summarized in a poster presentation preliminary data from the ongoing Phase 1/2 trial of CPI-0209, a novel, second-generation, small molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2). These data were published online in conjunction with the American Society of Clinical Oncology (ASCO) Annual Meeting, and show comprehensive target engagement and durable exposure of CPI-0209. Anti-tumor activity of CPI-0209 in pre-clinical models was demonstrated across several advanced hematologic and solid tumor types.

“We designed CPI-0209 to improve on first-generation EZH2 inhibitors in a number of ways, including increased potency, long residence time on target, and a lack of auto-induction of metabolism. These enhancements translate in the clinic, which we believe will be key to unlocking the full therapeutic potential of EZH2 inhibition,” said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. “I am also pleased that dosing is under way in our Phase 2 expansion cohorts at the selected dose.” 

Preliminary Data Highlights

  • A total of 40 patients were treated across 14 tumor types.
  • A 350mg oral, once-daily dose of CPI-0209 has been selected for evaluation in Phase 2.
  • As of the data cut of March 9, 2021, of the 4 BAP1 loss mesothelioma patients, 1 patient had a durable partial response (PR) after four cycles of treatment and 2 had stable disease (SD). Subsequently, to the data cut, the fourth patient also had SD.
  • High levels of target engagement observed preclinically are now corroborated clinically.


A total of 40 patients were evaluated for safety. CPI-0209 was generally well tolerated, with a manageable adverse event profile. Across all dose cohorts, 43% of patients had at least one Grade 3 or greater treatment emergent adverse event (TEAE), 28% of patients had at least one serious adverse event (SAE). The most common TEAEs (≥ 15%) included thrombocytopenia (reversible and dose dependent), diarrhea, asthenic conditions, nausea, anemia, dysgeusia, abdominal pain and alopecia. 23% of patients reported a TEAE that led to dose reduction or interruption. Four patients discontinued treatment because of TEAEs. One patient in the highest dose cohort (375mg) experienced Grade 4 thrombocytopenia, and one patient experienced a Grade 5 adverse event due to progressive disease.

For further details, please view the ASCO poster.

ASCO Poster Presentation

TITLE: Phase 1/2 First-in-Human Study of CPI-0209, a Novel Small Molecule Inhibitor of Enhancer of Zeste Homolog 2 (EZH2) in Patients with Advanced Tumors (Abstract Code 3104)

About CPI-0209

CPI-0209 is a second-generation EZH2 inhibitor 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 and a more comprehensive on-target action than first-generation EZH2 inhibitors, as well as robust anti-tumor activity in models of multiple hematologic and solid cancer types. 

About CPI-0209 clinical trial

The Phase 1 portion of the CPI-0209 Phase1/2 clinical trial is an open label, dose escalation study in patients with advanced tumors. A total of 41 patients were enrolled, of which 40 patients received CPI-0209. The primary objective of the Phase 1 portion is to evaluate safety and determine the recommended Phase 2 dose of CPI-0209.

The Phase 2 portion is an open label, single arm study, currently enrolling 20 to 29 patients per cohort in the following tumor types: relapsed urothelial carcinoma, relapsed ovarian clear cell carcinoma, and relapsed endometrial carcinoma all with known ARID1A mutation; relapsed or refractory lymphomas; malignant pleural or peritoneal mesothelioma with known BAP1 loss; as well as metastatic castration-resistant prostate cancer. The goal of these cohorts is to establish the safety and the antitumor activity of CPI-0209 as a monotherapy for patients with these tumor types.

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 BET inhibitor pelabresib for the treatment of myelofibrosis as well as the EZH2 inhibitor CPI-0209 for the treatment of advanced malignancies. 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.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the Company’s plans, strategies and prospects for its business and statements regarding the development status of the Company’s product candidates, the timing of availability of clinical trial data and the Company’s ability to fund its operations until the second half of 2022. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with: the Company’s ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; the Company’s ability to continue to advance its product candidates in clinical trials; whether preliminary or interim data from a clinical trial will be predictive of the final results of the trial; replication in later clinical trials positive results found in preclinical studies and early-stage clinical trials of CPI-0610, CPI-1205 and CPI-0209; the Company’s ability to advance the development of its product candidates under the timelines it anticipates, or at all, in current and future clinical trials; the Company’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; manage expenses; the Company’s ability to raise the substantial additional capital needed to achieve its business objectives; the COVID-19 pandemic and general economic and market conditions; and whether the previously announced acquisition of the Company by MorphoSys AG will be consummated on a timely basis. CPI-0610, CPI-1205 and CPI-0209 are investigational therapies and have not been approved by the FDA (or any other regulatory authority). For a discussion of other risks and uncertainties, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties, and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.


Kia Khaleghpour, Ph.D.
Vice President, Investor Relations and Communications
Constellation Pharmaceuticals
+1 617-844-6859

Helen O’Gorman
FTI Consulting
+1 718-408-0800