 Constellation has aligned with the FDA on the design of MANIFEST-2, the pivotal Phase 3 clinical trial for CPI-0610 expected to begin in 2H20 Constellation plans to explore additional indications for CPI-0610CAMBRIDGE, Mass., Aug. 05, 2020 GLOBE NEWSWIRE -- Constellation Pharmaceuticals, Inc. Nasdaq: CNST, a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today announced its second-quarter 2020 financial results. Constellation also announced its plans for a Phase 3 clinical trial of the BET inhibitor CPI-0610 following scientific advice and regulatory meetings with the U.S. Food and Drug Administration FDA.The Company is preparing to initiate a global, randomized, double-blind, pivotal Phase 3 clinical trial for CPI-0610, to be called MANIFEST-2, in the second half of 2020. MANIFEST-2 is designed to enroll approximately 310 JAK-inhibitor-naïve patients with advanced primary myelofibrosis MF, post-essential-thrombocythemia MF, or post-polycythemia-vera MF. Patients will be randomized 1:1 to CPI-0610 plus ruxolitinib or placebo plus ruxolitinib. The primary endpoint will be spleen volume reduction at 24 weeks, and the key secondary endpoint will be Total Symptom Score measured by Myelofibrosis Symptom Assessment Form version 4.0 at 24 weeks.The Company plans to continue to explore other regulatory pathways for bringing CPI-0610 to MF patients.Having seen signals of clinical benefit for CPI-0610 in patients with MF as well as preliminary evidence of disease modification, we are pleased that we have aligned with the FDA on the design of the pivotal trial, MANIFEST-2, said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. We look forward to continuing the constructive dialogue we have had with the FDA and are committed to bringing CPI-0610 to patients in need as soon as possible.Program UpdatesCPI-0610 On June 12, 2020, Constellation presented an update of MANIFEST data as of an April 17, 2020, data cutoff in three posters at the European Hematology Association meeting, which are shown on Constellations website. Constellation plans to provide its next MANIFEST update, including both clinical and translational data, by the end of 2020. To expand the use of CPI-0610 into indications for other hematologic malignancies, the Company announced today that it intends to explore the potential for CPI-0610 in approximately 20 patients with high-risk essential thrombocythemia ET who are intolerant of, or refractory to, hydroxyurea by initiating a new arm of MANIFEST in the second half of 2020.CPI-0209 We are currently conducting the Phase 1 dose escalation portion of a Phase 12 clinical trial of the EZH2 inhibitor CPI-0209 in solid tumors, which is proceeding as planned. After determining the recommended Phase 2 dose for the monotherapy, which we expect to accomplish in 2020, we intend to pursue monotherapy expansion arms in selected solid tumor indications with a biomarker enrichment strategy. We will also determine the recommended Phase 2 dose in combination therapy and then pursue expansion arms for this combination therapy.Leadership UpdatesDuring the second quarter, Constellation strengthened its board of directors and senior management with two appointments: On April 6, Dr. Richard Levy was appointed to the board of directors. Dr. Levy has nearly 30 years of experience in the pharmaceutical and biotechnology sectors, where he held senior clinical development positions at Incyte, Celgene, DuPont Pharmaceuticals, and Sandoz Novartis. He served as Executive Vice President and Chief Drug Development and Medical Officer at Incyte, where from 2003 to 2016 he was responsible for the expansion of the clinical development portfolio in oncology and inflammation. On June 22, Dr. Jeffrey Humphrey was appointed Chief Medical Officer. Dr. Humphrey is a medical oncologist with over 20 years of experience in drug development. Prior to joining Constellation, he was Chief Development Officer at Kyowa Kirin Co., where he oversaw development of the companys global portfolio of experimental therapeutics for Western markets. Dr. Humphrey began his work in industry clinical research at Bristol-Myers Squibb and subsequently served in management positions for early and late drug development and medical affairs at Pfizer, Bayer, and Bristol-Myers Squibb.MilestonesThe Company anticipates achieving the following milestones during 2020:CPI-0610 Initiate Phase 3 clinical trial in the second half of 2020CPI-0610 Provide additional MANIFEST program update by end of yearCPI-0209 Provide program update, including recommended Phase 2 dose, by end of yearSecond Quarter 2020 Financial Results Cash, cash equivalents, and marketable securities as of June 30, 2020, were 520.5 million, an increase of 35.6 compared to December 31, 2019, primarily due to gross proceeds of 192.5 million from the public offering in June 2020, offset by operating expenses. Research and development RD expenses increased 41.8 year over year to 22.6 million in the second quarter of 2020, mainly due to increased clinical trial expenses. General and administrative GA expenses grew 42.4 year over year to 7.0 million in the second quarter of 2020, primarily due to building out the organization of the company. The net loss attributed to common shareholders increased 43.3 year over year to 29.8 million for the second quarter of 2020, mainly due to increased RD and GA expenses. The net loss per share attributable to common shareholders decreased 12.5 to 0.70 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.First Half 2020 Financial Results Research and development RD expenses increased 35.0 year over year to 42.7 million in the first half of 2020, mainly due to increased clinical trial expenses. General and administrative GA expenses grew 38.1 year over year to 12.9 million in the first half of 2020, primarily due to building out the organization of the company. The net loss attributed to common shareholders increased 37.3 year over year to 55.2 million for the first half of 2020, mainly due to increased RD and GA expenses. The net loss per share attributable to common shareholders decreased 16.0 to 1.31 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 GuidanceConstellation expects that its current cash, cash equivalents, and marketable securities will fund operations into mid-2023.Results of Operations unaudited Six months ended June 30, Three months ended June 30, in thousands, except share and per-share amounts 2020 2019 2020 2019 Operating expenses: Research and development 42,702 31,632 22,627 15,955 General and administrative 12,868 9,315 6,960 4,886 Total operating expenses 55,570 40,947 29,587 20,841 Loss from operations 55,570 40,947 29,587 20,841 Other income expense: Interest income 2,090 1,407 686 652 Gain on disposal of equipment 29 29 Interest expense 1,707 653 857 578 Total other income expense, net 412 754 142 74 Loss before income taxes 55,158 40,193 29,729 20,767 Income tax expense 39 24 Net loss 55,197 40,193 29,753 20,767 Net loss per share attributable to common stockholders, basic and diluted 1.31 1.56 0.70 0.80 Weighted average number of common shares used in net loss per share attributable to common stockholders, basic and diluted 42,177,523 25,807,132 42,589,415 25,809,556 Comprehensive loss: Net loss 55,197 40,193 29,753 20,767 Other comprehensive gain: Unrealized gain on marketable securities 261 11 345 2 Total other comprehensive gain 261 11 345 2 Comprehensive loss 54,936 40,182 29,408 20,765 Consolidated Balance Sheets unaudited June 30, December 31, in thousands 2020 2019 Cash and cash equivalents 179,112 334,332 Marketable securities 341,401 49,602 Total current assets 523,099 386,989 Total assets 534,798 399,130 Current liabilities 27,284 22,755 Long-term debt, net of current portion and discount 27,569 29,642 Total liabilities 62,817 61,546 Total stockholders equity 471,981 337,584 Conference Call Constellation will host a conference call at 8:00 AM EDT on August 5, 2020, to discuss its clinical programs and financial results. The event will be webcast live and can be accessed on the Investor Relations section of Constellations website at 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 5692388.About Constellation PharmaceuticalsConstellation 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. 