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Dosing underway in the Phase 3 MANIFEST-2 clinical trial
Recommended Phase 2 dose determined for CPI-0209 and first patient dosed in the Phase 2 expansion cohorts
Upcoming data presentation at ASCO supports the best-in-class target engagement potential of CPI-0209
CAMBRIDGE, Mass., May 10, 2021 (GLOBE NEWSWIRE) -- Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today announced its first-quarter 2021 financial results. The Company also provided updates on its product candidates pelabresib and CPI-0209.
“Over the last year, we have advanced the development of pelabresib as a novel therapy for myelofibrosis, and we are pleased to be dosing patients in the Phase 3 MANIFEST-2 trial. Today we are also excited to announce progress on the Phase 2 development plan for our second generation EZH2 inhibitor, CPI-0209. We have determined the recommended Phase 2 dose and the expansion cohorts are open for enrollment, with the first patient dosed. We believe that CPI-0209 provides potential opportunities to treat a wide range of oncology patients,” said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. “These are important achievements in moving forward with our goal of becoming a fully integrated hematology / oncology company with a sustainable product pipeline.”
Dosing underway in the Phase 3 MANIFEST-2 clinical trial
On May 12, the Company expects the following three abstracts to be published in association with the European Hematology Association annual meeting, related to MANIFEST, the ongoing Phase 2 clinical trial of pelabresib:
TITLE: Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from MANIFEST Phase 2 study (Abstract Code: EP1077)
TITLE: Clinical benefit of pelabresib (CPI-0610) in combination with ruxolitinib in JAK inhibitor treatment naïve myelofibrosis patients: Interim efficacy subgroup analysis from Arm 3 of MANIFEST Phase 2 study (Abstract Code: EP1085)
TITLE: BET inhibitor pelabresib decreases inflammatory cytokines, improves bone marrow fibrosis and function, and demonstrates clinical response irrespective of mutation status in myelofibrosis patients (Abstract Code: EP1080)
The Company established the recommended Phase 2 dose (RP2D) of CPI-0209 monotherapy as 350 mg once daily. In the Phase 2 expansion cohorts, the Company plans to study CPI-0209 as a monotherapy in patients with cancers such as urothelial, ovarian clear cell and endometrial, where ARID1A mutations are prevalent, and lymphomas, where EZH2 mutations are prevalent. The first patient has been dosed in the expansion cohorts.
On April 10, a poster published in association with the American Association for Cancer Research (AACR) provided preclinical data suggesting that CPI-0209 has therapeutic potential in androgen receptor-positive prostate cancer.
On May 19, the Company expects the following abstract for a poster to be published in association with the American Society of Clinical Oncology (ASCO) annual meeting related to the Phase 1 portion of the Phase 1/2, clinical trial of CPI-0209:
TITLE: Phase 1/2 first-in-human (FIH) study of CPI-0209, a novel small molecule inhibitor of enhancer of zeste homolog 2 (EZH2) in patients with advanced tumors (Abstract Code: 3104)
The Company anticipates achieving the following milestones during 2021:
Pelabresib – Provide MANIFEST translational data update mid-year
Pelabresib – Provide MANIFEST clinical data update and update on new indications by end of year
CPI-0209 – Provide Phase 1 data update by mid-year
CPI-0209 – Provide update on monotherapy cohorts from Phase 2 by end of year
First Quarter 2021 Financial Results
Cash, cash equivalents, and marketable securities as of March 31, 2021, were $382.1 million, a decrease of 9.3% compared to December 31, 2020, primarily due to operating expenses.
Research and development (R&D) expenses increased 53.3% year over year to $30.8 million in the first quarter of 2021, mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 59.8% year over year to $9.4 million in the first quarter of 2021, primarily due to building out the organization of the company.
The net loss attributed to common shareholders increased 57.5% year over year to $40.1 million for the first quarter of 2021, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased 37.7% to $0.84 per share due to an increased net loss, partially offset by an increase in weighted average shares outstanding.
Constellation expects that its current cash, cash equivalents, and marketable securities will fund operations into mid-2023.
Results of Operations (unaudited)
Three months ended March 31,
(In thousands, except share and per-share amounts)
Research and development
General and administrative
Total operating expenses
Loss from operations
Other income (expense):
Total other income (expense), net
Loss before income taxes
Income tax expense
Net loss per share attributable to common stockholders,
Weighted average number of common shares used in net loss per share
Other comprehensive loss:
Unrealized loss on marketable securities
Total other comprehensive loss
Consolidated Balance Sheets (unaudited)
Cash and cash equivalents
Total current assets
Total stockholders’ equity
For further information, please refer to the financial statements filed with the SEC on Form 10-Q, including notes to the financials.
Constellation will host a conference call at 8:00 AM EDT on May 10, 2021, to discuss its clinical programs and financial results. The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at http://ir.constellationpharma.com/events-and-presentations/events. To participate in the live question-and-answer session, please dial (877) 473-2077 (domestic) or (661) 378-9662 (international) and refer to conference ID 8798968.
MANIFEST-2 is a global, blinded, randomized Phase 3 clinical trial with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-naïve patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have splenomegaly and symptoms requiring therapy. It is designed to enroll approximately 310 patients, randomized 1:1 to the pelabresib + ruxolitinib arm or the placebo + ruxolitinib arm. The primary endpoint of the study is a ≥35% reduction in spleen volume (SVR35) from baseline at 24 weeks. A key secondary endpoint of the study is 50% or greater improvement in Total Symptom Score (TSS50) from baseline at 24 weeks. Other endpoints include bone marrow fibrosis grade improvements, duration of transfusion independence, rate of red-blood-cell transfusion for the first 24 weeks, and hemoglobin response.
MANIFEST is an open-label Phase 2 clinical trial of pelabresib in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.
About CPI-0209 clinical trial
The Phase 2 portion of the Phase1/2 clinical trial of CPI- 0209 is an open label, single arm study, enrolling up to 29 patients per cohort in the following tumor types: relapsed urothelial carcinoma with known ARID1A mutation; relapsed ovarian clear cell carcinoma with known ARID1A mutation; relapsed endometrial carcinoma with known ARID1A mutation; relapsed or refractory lymphomas of either B-cell or T-cell histology. The goal of these cohorts is to establish the safety and establish 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.
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential of, and expectations for, the Company’s clinical development programs and regulatory plans, and beliefs about the timelines, progress, and prospects thereof; expectations as to the timing of availability of clinical trial data and plans for publications and presentations; and the Company’s financial guidance, including expectations as to its ability to fund its operations through mid-2023. 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; 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; replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials; advance the development of its product candidates under the timelines it anticipates, or at all, in current and future clinical trials; obtain, maintain, or protect intellectual property rights related to its product candidates; manage expenses; raise the substantial additional capital needed to achieve its business objectives; and the impact of the COVID-19 pandemic on the Company’s business and operations, including on its ongoing clinical trials and regulatory activities, and on the general economic and market conditions. Pelabresib 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
MacDougall Biomedical Communications