GlobeNewswire Inc | Aug 5, 2020 07:00AM EDT

August 05, 2020

-- 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-0610

CAMBRIDGE, 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-nave 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 Updates

CPI-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 1/2 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 Updates

During 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.

Milestones

The Company anticipates achieving the following milestones during 2020:

CPI-0610 Initiate Phase 3 clinical trial in the second half of 2020

CPI-0610 Provide additional MANIFEST program update by end of year

CPI-0209 Provide program update, including recommended Phase 2 dose, by end of year

Second Quarter 2020 Financial Results

-- Cash, cash equivalents, and marketable securities as ofJune 30, 2020, were $520.5 million, an increase of 35.6%compared toDecember 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 (R&D) expenses increased 41.8% year over year to$22.6 millionin the second quarter of 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew 42.4% year over year to $7.0 millionin 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 R&D and G&A 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 (R&D) expenses increased 35.0% year over year to$42.7 millionin the first half of 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew 38.1% year over year to $12.9 millionin 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 R&D and G&A 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 Guidance

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

Results of Operations (unaudited)

Six months ended Three months ended June 30, June 30,($ in thousands,except share and 2020 2019 2020 2019 per-share amounts)Operating expenses: Research and $ 42,702 $ 31,632 $ 22,627 $ 15,955 developmentGeneral and 12,868 9,315 6,960 4,886 administrativeTotal operating 55,570 40,947 29,587 20,841 expensesLoss from (55,570 ) (40,947 ) (29,587 ) (20,841 )operationsOther income (expense):Interest income 2,090 1,407 686 652 Gain on disposal of 29 ? 29 ? equipmentInterest expense (1,707 ) (653 ) (857 ) (578 )Total other income 412 754 (142 ) 74 (expense), netLoss before income (55,158 ) (40,193 ) (29,729 ) (20,767 )taxesIncome tax expense 39 ? 24 ? Net loss $ (55,197 ) $ (40,193 ) $ (29,753 ) $ (20,767 )Net loss per shareattributable tocommon $ (1.31 ) $ (1.56 ) $ (0.70 ) $ (0.80 )stockholders,basicand dilutedWeighted averagenumber of commonshares used in netloss per share 42,177,523 25,807,132 42,589,415 25,809,556 attributable tocommonstockholders, basicand diluted Comprehensive loss: Net loss $ (55,197 ) $ (40,193 ) $ (29,753 ) $ (20,767 )Other comprehensive gain:Unrealized gain onmarketable 261 11 345 2 securitiesTotal other $ 261 $ 11 $ 345 $ 2 comprehensive gainComprehensive 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 27,569 29,642 discountTotal 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 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 5692388.

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.

Forward-Looking Statements

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 Companys clinical development and regulatory plans, timelines, and prospects, the timing of availability of clinical trial data and the Companys ability to fund its operations thru mi-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 managements 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 Companys 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 of CPI-0610 and CPI-0209; 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; the COVID-19 pandemic and general economic and market conditions. 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 Companys 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 Companys most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Companys views as of the date hereof and should not be relied upon as representing the Companys views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Companys 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.

Contacts

Kia Khaleghpour, Ph.D.Vice President, Investor Relations and CommunicationsConstellation Pharmaceuticals+1 617-844-6859kia.khaleghpour@constellationpharma.com

Ronald AldridgeSenior Director, Investor Relations Constellation Pharmaceuticals+1 617-714-0539ron.aldridge@constellationpharma.com

Lauren ArnoldMedia RelationsMacDougall Biomedical Communications+1 781-235-3060larnold@macbiocom.com