GlobeNewswire Inc | Feb 24, 2021 07:00AM EST

February 24, 2021

CAMBRIDGE, Mass., Feb. 24, 2021 (GLOBE NEWSWIRE) -- Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today announced itsfourth-quarter 2020 financial results and provided a business update.

2020 was an important year for Constellation Pharmaceuticals, marked by several presentations of strong data from our MANIFEST clinical trial for pelabresib (formerly CPI-0610), including our oral presentations at the ASH Annual Meeting, said Jigar Raythatha, President and Chief Executive Officer of Constellation Pharmaceuticals. We are executing on our recently launched Phase 3 trial, MANIFEST-2 and believe pelabresib has the potential to transform the standard of care in myelofibrosis. We also continue to advance our pipeline of product candidates with CPI-0209 and the newly announced CPI-482.

Pelabresib (CPI-0610)

-- Constellation presented an update of MANIFEST data in two oral presentations and three posters at the American Society of Hematology 2020 Annual Meeting, which are available on Constellations website.

CPI-0209

-- Patients continue to be advanced through multiple dosing cohorts in thePhase 1dose escalation portion of a Phase 1/2clinical trialofthe EZH2 inhibitorCPI-0209. -- Data from the Phase 1 portion will guide our recommended Phase 2 dose (RP2D) selection for expansion arms in select tumor types. -- Clinical data will be supplementedwith data on biomarkers to identify patients most likely to benefit.

CPI-482

-- The Company named CPI-482 as a new development candidate, targeting LSD1. CPI-482 reinforces our commitment to addressing unmet needs in hematologic diseases, particularly myeloproliferative neoplasms (MPNs). Furthermore, our development strategy with CPI-482 will leverage our unique translational research and understanding of epigenetic mechanisms in myeloid cells.

2020 Leadership Updates

-- Constellation strengthened its senior management team with the appointment of Brendan Delaney as Chief Commercial Officer, effective January 2021. Previously, Mr. Delaney served as Chief Commercial Officer of Immunomedics and Vice President, U.S. Commercial Hematology Oncology at Celgene. Mr. Delaney will build and lead the Companys commercial organization and pre-launch preparations in support of pelabresib. -- Earlier in the year, Constellation appointed Jeffrey Humphrey, M.D. as Chief Medical Officer. Previously, Dr. Humphrey served as Chief Development Officer at Kyowa Kirin Co., where he oversaw the development of over twenty drug candidates including regulatory submissions leading to three drug approvals inthe United Statesand Europe.

2021 Milestones

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

FourthQuarter 2020 Financial Results

-- Cash, cash equivalents, and marketable securities as ofDecember31, 2020, were $421.4million. -- Research and development (R&D) expenses increased47.2% year over year to$27.4millionin thefourth quarterof 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew56.2% year over year to $8.5millionin thefourth quarterof 2020, primarily due to building out the organization of the company. -- The net loss attributed to common shareholders increased54.4% year over year to$37.4million for thefourth quarterof 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased by14.5% to $0.79 per share, due to an increase in net loss and partly off-set by an increase in weighted shares outstanding.

Full Year 2020 Financial Results

-- Research and development (R&D) expenses increased 43.7% year over year to$95.5 millionfor full-year 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew 49.8% year over year to$29.3millionfor full-year 2020, primarily due to building out the organization of the company. -- The net loss attributed to common shareholders increased 47.7% year over year to$126.4 million for full-year 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased 7.6% to$2.81 per share, largely due to an increase in weighted average shares outstanding as a result of the additional shares issued in June 2020.

Financial Guidance

Constellationexpects that its current cash, cash equivalents, and marketable securities balance will fund operationsintomid-2023.

Results of Operations (unaudited)

Years ended December 31, Three months ended December 31,(In thousands,except share 2020 2019 2020 2019 and per-shareamounts)Operating expenses:Research and $ 95,501 $ 66,459 $ 27,356 $ 18,586 developmentGeneral and 29,346 19,596 8,543 5,471 administrativeTotaloperating 124,847 86,055 35,899 24,057 expensesLoss from (124,847 ) (86,055 ) (35,899 ) (24,057 )operationsOther income (expense):Interest 2,851 2,644 302 730 incomeGain ondisposal of 41 ? 12 - equipmentLoss onextinguishment (1,501 ) ? (1,501 ) - of debtInterest (2,862 ) (2,115 ) (298 ) (857 )expenseTotal otherincome (1,471 ) 529 (1,485 ) (127 )(expense), netLoss before (126,318 ) (85,526 ) (37,384 ) (24,184 )income taxesIncome tax 39 24 ? 24 expenseNet loss $ (126,357 ) $ (85,550 ) $ (37,384 ) $ (24,208 )Net loss pershareattributableto common $ (2.81 ) $ (3.04 ) $ (0.79 ) $ (0.69 )stockholders,basic anddilutedWeightedaverage numberof commonshares used innet loss pershare 44,890,425 28,151,763 47,612,703 35,086,817 attributableto commonstockholders,basic anddiluted Comprehensive loss:Net loss $ (126,357 ) $ (85,550 ) $ (37,384 ) $ (24,208 )Othercomprehensive gain (loss):Unrealizedgain (loss) on 9 (6 ) (131 ) (7 )marketablesecuritiesTotal othercomprehensive $ 9 $ (6 ) $ (131 ) $ (7 )gain (loss)Comprehensive $ (126,348 ) $ (85,556 ) $ (37,515 ) $ (24,215 )loss

Consolidated Balance Sheets (unaudited)

December 31, (In $ thousands) 2020 2019 Cash and cash equivalents $ 163,693 $ 334,332 Marketable securities 257,755 49,602 Total current assets 428,609 386,989 Total assets 441,854 399,130 Current liabilities 30,548 22,755 Long-term debt, net of current portion ? 29,642 and discountTotal liabilities 31,130 61,546 Total stockholders? equity $ 410,724 $ 337,584

Conference Call

Constellationwill host a conference call at8:00AM EDT onFebruary 24, 2021,to discuss its clinical programsand 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 ID6971724.

About MANIFEST-2

MANIFEST-2 is a global, blinded, randomized Phase 3 clinical study with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-nave 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.

About MANIFEST

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 bodys normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-nave 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 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 inhibitorCPI-0209 for the treatment ofadvanced 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 The Private Securities Litigation Reform Act of 1995that involve substantial risks and uncertainties, including statements regardingthe Companysclinical development and regulatoryplans, timelines,and prospects,the timing of availability of clinical trial data and the Companys ability to funditsoperationsthru 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 managements current expectations of future events and are subject toa number ofrisks 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 pelabresib, CPI-0209 and CPI-482; 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 thesubstantial additional capital needed to achieve its business objectives; and the COVID-19 pandemic and 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 Companys actual results to differ from those contained in the forward-looking statements, see theRisk Factorssection, as well as discussions of potential risks, uncertainties, and other important factors, in the Companys most recentfilings with theSecurities 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 datesubsequent tothe 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 Relationsand CommunicationsConstellation Pharmaceuticals+1 617-844-6859kia.khaleghpour@constellationpharma.com

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