CNST Constellation Pharmaceuticals Inc

Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today announced its fourth-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 Constellation’s website.

CPI-0209 

• Patients continue to be advanced through multiple dosing cohorts in the Phase 1 dose escalation portion of a Phase 1/2 clinical trial of the EZH2 inhibitor CPI-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 supplemented with 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 Company’s 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 in the United States and 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

Fourth Quarter 2020 Financial Results 

• Cash, cash equivalents, and marketable securities as of December 31, 2020, were $421.4 million.  
• Research and development (R&D) expenses increased 47.2% year over year to $27.4 million in the fourth quarter of 2020, mainly due to increased clinical trial expenses. 
• General and administrative (G&A) expenses grew 56.2% year over year to $8.5 million in the fourth quarter of 2020, primarily due to building out the organization of the company. 
• The net loss attributed to common shareholders increased 54.4% year over year to $37.4 million for the fourth quarter of 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased by 14.5% 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 million for full-year 2020, mainly due to increased clinical trial expenses.
• General and administrative (G&A) expenses grew 49.8% year over year to $29.3 million for 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  Constellation expects that its current cash, cash equivalents, and marketable securities balance will fund operations into mid-2023. 

Results of Operations (unaudited) 

		Years ended December 31,								Three months ended December 31,
(In thousands, except share and per-share amounts)		2020				2019				2020				2019
Operating expenses:
Research and development		$	95,501			$	66,459			$	27,356			$	18,586
General and administrative			29,346				19,596				8,543				5,471
Total operating expenses			124,847				86,055				35,899				24,057
Loss from operations			(124,847	)			(86,055	)			(35,899	)			(24,057	)
Other income (expense):
Interest income			2,851				2,644				302				730
Gain on disposal of equipment			41				—				12				-
Loss on extinguishment of debt			(1,501	)			—				(1,501	)			-
Interest expense			(2,862	)			(2,115	)			(298	)			(857	)
Total other income (expense), net			(1,471	)			529				(1,485	)			(127	)
Loss before income taxes			(126,318	)			(85,526	)			(37,384	)			(24,184	)
Income tax expense			39				24				—				24
Net loss		$	(126,357	)		$	(85,550	)		$	(37,384	)		$	(24,208	)
Net loss per share attributable to common stockholders,basic and diluted		$	(2.81	)		$	(3.04	)		$	(0.79	)		$	(0.69	)
Weighted average number of common shares used in net loss per shareattributable to common stockholders, basic and diluted			44,890,425				28,151,763				47,612,703				35,086,817
Comprehensive loss:
Net loss		$	(126,357	)		$	(85,550	)		$	(37,384	)		$	(24,208	)
Other comprehensive gain (loss):
Unrealized gain (loss) on marketable securities			9				(6	)			(131	)			(7	)
Total other comprehensive gain (loss)		$	9			$	(6	)		$	(131	)		$	(7	)
Comprehensive loss		$	(126,348	)		$	(85,556	)		$	(37,515	)		$	(24,215	)

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 and discount			—				29,642
Total liabilities			31,130				61,546
Total stockholders’ equity		$	410,724			$	337,584

Conference Call  

Constellation will host a conference call at 8:00 AM EDT on February 24, 2021, to discuss its clinical programs and financial results. The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s 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 6971724.  

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-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 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 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 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 inhibitor CPI-0209 for the treatment of advanced 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 1995 that involve substantial risks and uncertainties, including statements regarding the Company’s clinical development and regulatory plans, timelines, and prospects, the timing of availability of clinical trial data and the Company’s ability to fund its operations thru 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 management’s 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 Company’s 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 the substantial 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 Company’s 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 Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s 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 Communications Constellation Pharmaceuticals +1 617-844-6859 kia.khaleghpour@constellationpharma.com   Lauren Arnold Media Relations MacDougall Biomedical Communications +1 781-235-3060 larnold@macbiocom.com