On March 14, 2019 March 14, 2019 (GLOBE NEWSWIRE) — Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its fourth-quarter and full-year 2018 financial results (Press release, Constellation Pharmaceuticals, MAR 14, 2019, View Source [SID1234534359]).
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"2019 is a year of data for Constellation, and our clinical programs are making significant progress and approaching important readouts," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals.
"We are excited by preliminary data from our first four patients from the MANIFEST clinical trial, each showing one or more of the following: conversion from transfusion dependence to transfusion independence, hemoglobin increases, improvements in bone marrow fibrosis scores, spleen reductions, and symptom improvements. These results taken together suggest that CPI-0610 may have disease-modifying effects in myelofibrosis patients. We plan to present an interim update of data from MANIFEST from approximately 18-20 evaluable patients at a medical meeting in the second quarter of 2019.
"We also plan to present Phase 1b data from the ProSTAR clinical trial of CPI-1205 in metastatic castration-resistant prostate cancer in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting on April 1. Enrollment is on track in the Phase 2 portion of the ProSTAR trial, and we expect to provide an interim update of data of the Phase 2 portion at a medical meeting in the second half of 2019," Mr. Raythatha continued.
"The Constellation team continues to work diligently toward becoming a late-stage oncology development company and bringing important new medicines to underserved cancer patients," Mr. Raythatha concluded.
Recent News
MANIFEST
Enrollment is on track in the MANIFEST clinical trial in myelofibrosis patients. The Company has now opened approximately 20 clinical trial sites in the U.S., Canada, and Europe. As of February 28, 2019, 28 patients had been enrolled in the second-line arms of MANIFEST. The Company plans to provide an update on approximately 18-20 evaluable patients with at least three months of data at a second quarter medical meeting.
Each of the first four patients in MANIFEST remains on study. As of the last data cutoff on December 10, 2018, the first two patients treated with a combination of CPI-0610 and ruxolitinib had been treated for over 16 months. The first two patients treated with CPI-0610 monotherapy had been treated for over 12 months. As previously reported, each of these four patients has shown a reduction in spleen volume and improved hemoglobin levels. One of the combination therapy patients was transfusion dependent before therapy and converted to being transfusion independent after CPI-0610 was added to the patient’s regimen. As of December 10, 2018, this patient had been free of transfusions for over 52 weeks. Additionally, bone marrow biopsies before and after treatment were analyzed for the first two evaluable patients on monotherapy, and both demonstrated a one-grade improvement in bone marrow fibrosis score as well as associated improvements in hemoglobin. Taken together, these results suggest that CPI-0610 may be improving bone marrow function in these ruxolitinib-resistant MF patients.
We believe CPI-0610 has the potential for a differentiated toxicity profile compared with other BET inhibitors. In a Phase 1 clinical trial, the Company showed that the dose-limiting toxicity for BET inhibitors of thrombocytopenia was reversible and non-cumulative for CPI-0610. In addition, preliminary data suggest that CPI-0610 may have a wider therapeutic window relative to some other BET inhibitors, based on their published data. The recommended Phase 2 dose of CPI-0610 in the MANIFEST study is 125 mg once daily, with titration allowed up to 225 mg once daily, which is the maximum tolerated dose.
ProSTAR
Constellation plans to provide an update of Phase 1b data for ProSTAR in a poster at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Atlanta on April 1.
The Phase 2 portion of the ProSTAR clinical trial continues to enroll patients in line with the Company’s plans. Constellation plans to present an interim update of data of the Phase 2 portion of ProSTAR at a medical meeting in the second half of 2019.
Constellation recently began dosing in heavily pretreated patients in a new arm of ProSTAR. Previously, a compassionate-use patient, who had experienced disease progression despite treatment with 12 agents (including abiraterone, enzalutamide, and chemotherapy) prior to CPI-1205, experienced an 80% reduction in PSA levels and evidence of tumor size reduction in the neck lymph nodes when treated with CPI-1205 in combination with enzalutamide. The new treatment arm will enroll up to 30 patients in a single arm of CPI-1205 in combination with enzalutamide in heavily pretreated patients.
Corporate
On February 20, Constellation announced that Dr. Scott Braunstein was appointed to the Board of Directors. Dr. Braunstein is also a member of the Audit Committee. Dr Braunstein has an impressive track record of helping emerging and established biopharmaceutical companies as an investor and a pharmaceutical executive.
On March 1, Jessica Christo was appointed Chief Product Development Officer. Ms. Christo brings to Constellation 25 years of product development experience in the biopharmaceutical industry in clinical operations, data management, program management, biostatistics, and related fields.
Fourth Quarter 2018 Financial Results
Cash and cash equivalents as of December 31, 2018 decreased 10.8% to $114.6 million compared to September 30, 2018, primarily due to operating expenses.
Research and development (R&D) expenses increased 65.4% year over year to $16.6 million in the fourth quarter of 2018 mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 118.3% year over year to $4.0 million in the fourth quarter of 2018, primarily due to costs related to building out the organization as the Company evolved from a preclinical-stage company to a multi-candidate clinical-stage company, as well as costs associated with operating as a public company.
The net loss attributable to common stockholders increased 17.5% year over year to $19.9 million mainly due to increases in G&A and R&D expenses, partly offset by the inclusion of unpaid cumulative dividends in 2017 that were waived in 2018. The net loss per share attributable to common stockholders decreased 95.6% to $0.77 per share for the fourth quarter of 2018 due to an increase in shares outstanding as a result of the initial public offering and conversion of the preferred stock to common stock.
Full-Year 2018 Financial Results
Research and development (R&D) expenses increased 49.5% year over year to $48.8 million in 2018 mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 92.8% year over year to $12.5 million in 2018, primarily due to costs related to building out the organization as the Company evolved from a preclinical-stage company to a multi-candidate clinical-stage company, as well as costs associated with operating as a public company.
The net loss attributable to common stockholders increased 11.5% year over year to $59.9 million mainly due to increases in G&A and R&D expenses, partly offset by the inclusion of unpaid cumulative dividends in 2017 that were waived in 2018. The net loss per share attributable to common stockholders decreased 91.1% to $5.00 per share for 2018 due to an increase in shares outstanding as a result of the initial public offering and conversion of the preferred stock to common stock.
Financial Guidance
We expect that our cash and cash equivalents as of December 31, 2018, will fund operating expenses and capital expenditure requirements into the second quarter of 2020.
Anticipated Milestones
The Company anticipates achieving the following milestones during 2019:
First Half 2019
Provide a data update from the Phase 1b portion of the ProSTAR trial for CPI-1205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting on April 1
Provide an interim update of data from the MANIFEST Phase 2 trial of CPI-0610 at a second-quarter 2019 medical meeting
Initiate a Phase 1 trial for CPI-0209
Second Half 2019
Provide an interim update of data from the Phase 2 portion of the ProSTAR trial for CPI-1205
Provide an additional data update from the MANIFEST trial for CPI-0610
Financial Results (Unaudited)
Constellation Pharmaceuticals, Inc.
Consolidated Statements of Operations and Comprehensive Loss
Years ended
December 31, Three months ended
December 31,
(In thousands, except share and per-share amounts) 2018 2017 2018 2017
Revenue $ — $ — $ — $ —
Operating expenses:
Research and development 48,769 32,617 16,626 10,053
General and administrative 12,475 6,471 4,006 1,835
Total operating expenses 61,244 39,088 20,632 11,888
Loss from operations (61,244 ) (39,088 ) (20,632 ) (11,888 )
Other income (expense):
Interest income 1,547 169 688 58
Interest expense (228 ) (901 ) — (102 )
Change in fair value of preferred stock tranche liability — 4,443 — —
Total other income (expense), net 1,319 3,711 688 (44 )
Net loss and comprehensive loss (59,925 ) (35,377 ) (19,944 ) (11,932 )
Cumulative dividends on convertible preferred stock — (18,390 ) — (5,048 )
Net loss attributable to common stockholders (59,925 ) (53,767 ) (19,944 ) (16,980 )
Net loss per share attributable to common stockholders, basic and diluted $ (5.00 ) $ (56.10 ) $ (0.77 ) $ (17.64 )
Weighted average common shares outstanding, basic and diluted 11,984,293 958,447 25,789,305 962,330
Constellation Pharmaceuticals, Inc.
Consolidated Balance Sheets
(In $ thousands) December 31,
2018 December 31,
2017
Cash and cash equivalents 114,592 16,404
Other current assets 2,711 1,318
Total assets 118,938 19,103
Current liabilities 14,660 11,131
Total liabilities 14,780 11,708
Convertible preferred stock — 173,228
Total stockholders’ equity (deficit) 104,158 (165,833 )
Note: Abbreviated financial statements; please refer to Form 10-K for more details, including explanatory notes.