GlobeNewswire Inc | Oct 29, 2020 07:01AM EDT

October 29, 2020

-- MANIFEST data update planned for the American Society of Hematology (ASH) meeting in December

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 itsthird-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-nave 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 Companys 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-nave 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-Nave Myelofibrosis Patients: Update of MANIFEST Phase 2 StudyOral Session: 634. Myeloproliferative Syndromes: Clinical: New Therapies and JAKi-based Combinations for MyelofibrosisDate and Time: December 5, 2020, 11:30 AM ESTPresenter: 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 StudyOral Session: 634. Myeloproliferative Syndromes: Clinical: New Therapies and JAKi-based Combinations for MyelofibrosisDate and Time: December 5, 2020, 11:45 AM ESTPresenter: 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 IIDate and Time: Sunday, December 6, 2020, 10:00 AM-6:30 PM ESTPresenter: 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-Nave Myelofibrosis Patients Session: 634. Myeloproliferative Syndromes: Clinical: Poster IIIDate and Time: Monday, December 7, 2020, 10:00 AM-6:30 PM ESTPresenter: 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 CellsSession: 634. Myeloproliferative Syndromes: Clinical: Poster IIIDate and Time: Monday, December 7, 2020, 10:00 AM-6:30 PM ESTPresenter: Dr. Mohamed Salama, Professor of Pathology and Laboratory Medicine, Mayo Clinic School of Medicine

CPI-0209

-- ThePhase 1dose escalation portion of a Phase 1/2clinical trialofthe EZH2 inhibitorCPI-0209is 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 supplementedwith data on biomarkers to identify patients most likely to benefit.

ThirdQuarter 2020 Financial Results

-- Cash, cash equivalents, and marketable securities as ofSeptember30, 2020, were $489.4million. -- Research and development (R&D) expenses increased56.7% year over year to$25.4millionin thethird quarterof 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew65.0% year over year to $7.9millionin thethird quarterof 2020, primarily due to building out the organization of the company. -- The net loss attributed to common shareholders increased59.7% year over year to$33.8million for thethird quarterof 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased13.4% 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 Month2020 Financial Results

-- Research and development (R&D) expenses increased42.3% year over year to$68.1millionin thefirst nine months of 2020, mainly due to increased clinical trial expenses. -- General and administrative (G&A) expenses grew47.3% year over year to $20.8millionin thefirst nine months of 2020, primarily due to building out the organization of the company. -- The net loss attributed to common shareholders increased45.0% year over year to$89.0million for thefirst nine months of 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased15.1% to $2.02per share due to an increase in shares outstanding as a result of the private placement in October 2019 and the public offeringsin December 2019and June 2020, offset in part by the increased net loss.

Financial Guidance

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

Results of Operations (unaudited)

Nine months ended Three months ended September 30, September 30,(In thousands,except share 2020 2019 2020 2019 and per-shareamounts)Operating expenses:Research and $ 68,145 $ 47,873 $ 25,443 $ 16,241 developmentGeneral and 20,803 14,125 7,935 4,810 administrativeTotaloperating 88,948 61,998 33,378 21,051 expensesLoss from (88,948 ) (61,998 ) (33,378 ) (21,051 )operationsOther income (expense):Interest 2,549 1,914 459 507 incomeGain ondisposal of 29 ? ? ? equipmentInterest (2,564 ) (1,258 ) (857 ) (605 )expenseTotal otherincome 14 656 (398 ) (98 )(expense), netLoss before (88,934 ) (61,342 ) (33,776 ) (21,149 )income taxesIncome tax 39 ? ? ? expenseNet loss $ (88,973 ) $ (61,342 ) $ (33,776 ) $ (21,149 )Net loss pershareattributableto common $ (2.02 ) $ (2.38 ) $ (0.71 ) $ (0.82 )stockholders,basic anddilutedWeightedaverage numberof commonshares used innet loss pershare 43,976,371 25,814,593 47,534,964 25,829,105 attributableto commonstockholders,basic anddiluted Comprehensive loss:Net loss $ (88,973 ) $ (61,342 ) $ (33,776 ) $ (21,149 )Othercomprehensive gain (loss):Unrealizedgain (loss) on 140 1 (121 ) (10 )marketablesecuritiesTotal othercomprehensive $ 140 $ 1 $ (121 ) $ (10 )gain (loss)Comprehensive $ (88,833 ) $ (61,341 ) $ (33,897 ) $ (21,159 )loss

Consolidated Balance Sheets (unaudited)

September 30, December 31,(In $ thousands) 2020 2019Cash and cash equivalents $ 116,996 $ 334,332Marketable securities 372,358 49,602Total current assets 494,466 386,989Total assets 505,449 399,130Current liabilities 31,274 22,755Long-term debt, net of current portion and 24,088 29,642discountTotal liabilities 62,679 61,546Total stockholders? equity $ 442,770 $ 337,584

Conference Call

Constellationwill host a conference call at8:00AM EDT onOctober 29, 2020,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 ID7374769.

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 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 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-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 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 inhibitorCPI-0209 for the treatment ofsolid 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 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 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 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 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 thesubstantial 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 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

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

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