On August 5, 2020 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported 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) (Press release, Constellation Pharmaceuticals, AUG 5, 2020, View Source [SID1234562867]).

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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 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 (EHA) (Free EHA Whitepaper) meeting, which are shown on Constellation’s 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 company’s 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 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 (R&D) 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 (G&A) 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 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 million in 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 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 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

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

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 Constellation’s website at View Source 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.