CAMBRIDGE, Mass., Oct. 29, 2020 (GLOBE NEWSWIRE) -- Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today announced its third-quarter 2020 financial results. The Company also provided updates on its product candidates CPI-0610 and CPI-0209.

“Many myelofibrosis patients continue to have significant unmet needs despite available therapy,” said Jeff Humphrey, M.D., Chief Medical Officer of Constellation Pharmaceuticals. “Constellation and leading clinical investigators are eager to enroll patients in MANIFEST-2, our pivotal Phase 3 study, to potentially define a new standard of care for MF patients.”

“We look forward to providing an update of MANIFEST data for CPI-0610 at the upcoming ASH conference,” said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. “We believe that CPI-0610 has the potential to modify the course of myelofibrosis by providing benefits across all four hallmarks of the disease: spleen volume reduction, symptom improvement, hemoglobin increases, and bone marrow fibrosis improvement.”

CPI-0610

• Constellation plans to provide its next MANIFEST data update at the American Society of Hematology (ASH) in December 2020, including 24-week data for SVR35 (?35% spleen volume reduction) and TSS50 (50% improvement in Total Symptom Score) from 50-60 first-line and 90-100 second-line myelofibrosis patients.
• Two oral presentations will focus on clinical data from JAK-inhibitor-naïve MF patients (Arm 3) and JAK-inhibitor-experienced MF patients being treated with CPI-0610 as an add-on to ruxolitinib (Arm 2).
• Three poster presentations will focus on translational data, clinical data from second-line patients being treated with CPI-0610 monotherapy (Arm 1), and the Phase 3 MANIFEST-2 trial in progress.
• The Company will also hold an investor event on December 7, 2020, to discuss these data. Event details will be provided later.
• Abstracts to be published on November 5, 2020, will be based on the April 17, 2020, data cutoff also used for the Company’s presentation at the European Hematology Association meeting in June 2020. Updated data will be presented at the ASH meeting.
• Patient enrollment in Arm 3 of MANIFEST, the Phase 2 clinical trial for CPI-0610, has been completed at approximately 80 JAK-inhibitor-naïve MF patients.
• MANIFEST-2, the pivotal Phase 3 trial for CPI-0610, remains on track to begin patient enrollment in the fourth quarter of 2020.

ASH Oral Presentations

Title: CPI-0610, a Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, in Combination with Ruxolitinib, in JAK-Inhibitor-Naïve Myelofibrosis Patients: Update of MANIFEST Phase 2 Study
Oral Session: 634. Myeloproliferative Syndromes: Clinical: New Therapies and JAKi-based Combinations for Myelofibrosis
Date and Time: December 5, 2020, 11:30 AM EST
Presenter: Dr. John Mascarenhas, Associate Professor of the Icahn School of Medicine at Mount Sinai

Title: CPI-0610, Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, As “Add-on” to Ruxolitinib, in Advanced Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST Phase 2 Study
Oral Session: 634. Myeloproliferative Syndromes: Clinical: New Therapies and JAKi-based Combinations for Myelofibrosis
Date and Time: December 5, 2020, 11:45 AM EST
Presenter: Dr. Srdan Verstovsek, Medical Oncologist, MD Anderson Cancer Center

ASH Poster Presentations

Title: CPI-0610, a Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, As Monotherapy in Advanced Myelofibrosis Patients Refractory / Intolerant to JAK Inhibitor: Update from Phase 2 MANIFEST Study
Session: 634. Myeloproliferative Syndromes: Clinical: Poster II
Date and Time: Sunday, December 6, 2020, 10:00 AM-6:30 PM EST
Presenter: Dr. Moshe Talpaz, Professor of Leukemia Research and Professor of Internal Medicine, University of Michigan Medical School

Title: MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of CPI-610 and Ruxolitinib Vs. Placebo and Ruxolitinib in JAK-Inhibitor-Naïve Myelofibrosis Patients
Session: 634. Myeloproliferative Syndromes: Clinical: Poster III
Date and Time: Monday, December 7, 2020, 10:00 AM-6:30 PM EST
Presenter: Dr. John Mascarenhas, Associate Professor of the Icahn School of Medicine at Mount Sinai

Title: The BET Inhibitor, CPI-0610, Promotes Myeloid Differentiation in Myelofibrosis Patient Bone Marrow and Peripheral CD34+ Hematopoietic Stem Cells
Session: 634. Myeloproliferative Syndromes: Clinical: Poster III
Date and Time: Monday, December 7, 2020, 10:00 AM-6:30 PM EST
Presenter: Dr. Mohamed Salama, Professor of Pathology and Laboratory Medicine, Mayo Clinic School of Medicine

CPI-0209

• The Phase 1 dose escalation portion of a Phase 1/2 clinical trial of the EZH2 inhibitor CPI-0209 is progressing well. Patient dosing has advanced through multiple dosing cohorts as planned.
• Data from the Phase 1 portion will guide our recommended Phase 2 dose selection for monotherapy and combination expansion arms in select tumor types.
• Clinical data will be supplemented with data on biomarkers to identify patients most likely to benefit.

Third Quarter 2020 Financial Results

• Cash, cash equivalents, and marketable securities as of?September 30, 2020, were $489.4 million.?
• Research and development (R&D) expenses increased 56.7% year over year to?$25.4 million?in the third quarter of 2020, mainly due to increased clinical trial expenses.
• General and administrative (G&A) expenses grew 65.0% year over year to $7.9 million?in the third quarter of 2020, primarily due to building out the organization of the company.
• The net loss attributed to common shareholders increased 59.7% year over year to?$33.8 million for the third quarter of 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased 13.4% to $0.71 per share due to an increase in shares outstanding as a result of the private placement in October 2019 and the public offerings in December 2019 and June 2020, offset in part by the increased net loss.

Nine Month 2020 Financial Results

• Research and development (R&D) expenses increased 42.3% year over year to?$68.1 million?in the first nine months of 2020, mainly due to increased clinical trial expenses.
• General and administrative (G&A) expenses grew 47.3% year over year to $20.8 million?in the first nine months of 2020, primarily due to building out the organization of the company.
• The net loss attributed to common shareholders increased 45.0% year over year to?$89.0 million for the first nine months of 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased 15.1% to $2.02 per share due to an increase in shares outstanding as a result of the private placement in October 2019 and the public offerings in December 2019 and June 2020, offset in part by the increased net loss.

Financial Guidance

Constellation?expects that its current cash, cash equivalents, and marketable securities will fund operations into mid-2023.

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 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 MANIFEST-2

MANIFEST-2 is a global, blinded, randomized, Phase 3 clinical study with CPI-0610 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 CPI-0610 + 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.

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 CPI-0610 for the treatment of myelofibrosis as well as the EZH2 inhibitor CPI-0209 for the treatment of solid tumors. 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.