On November 6, 2019 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its third-quarter and nine-month 2019 financial results (Press release, Constellation Pharmaceuticals, NOV 6, 2019, View Source [SID1234550453]).
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"Our clinical programs continued to advance during the third quarter," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "We are particularly pleased with new MANIFEST data on CPI-0610 in myelofibrosis published today in abstracts by the American Society of Hematology (ASH) (Free ASH Whitepaper). The data in the abstracts show signs of encouraging clinical activity in both JAK-inhibitor-naïve patients and ruxolitinib-refractory or -intolerant patients. Based on this activity, we have expanded the MANIFEST trial in first-line patients and in second-line transfusion-dependent patients to look more closely at these signals of activity. We plan to provide a further update on CPI-0610 in oral and poster presentations and at an investor event at the ASH (Free ASH Whitepaper) meeting on December 9. Additionally, we have begun planning for a randomized Phase 3 clinical trial for CPI-0610 in JAK-inhibitor-naïve patients that we expect to begin in 2020."
Program Updates
CPI-0610
Two abstracts with preliminary data from the MANIFEST clinical trial from 59 enrolled patients as of June 27, 2019, the data cutoff date, were published today in association with ASH (Free ASH Whitepaper). The following are highlights from the abstracts:
In Arm 3, in which we are evaluating CPI-0610 in combination with ruxolitinib in a first-line setting in JAK-inhibitor-naïve patients, all four evaluable patients experienced at least a 35% spleen volume reduction and at least a 50% reduction in total symptom score, which are the primary endpoints for these patients.
In Arms 1 and 2, in which we are evaluating CPI-0610 in combination with ruxolitinib and as a monotherapy in a second-line setting in ruxolitinib-resistant or -intolerant patients, additional preliminary data showed continuing signs of activity across a broad range of parameters, including spleen volume reduction, patient-reported symptom improvement, hemoglobin increases, conversion to transfusion independence in transfusion-dependent patients, and bone marrow fibrosis score improvement, consistent with preliminary data presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) in June.
In Arms 1 and 2, conversions to transfusion independence increased from two as of April 17, 2019, to four as of June 27, 2019. Data from 12 additional patients are being monitored for possible additional conversions.
CPI-0610 was generally well-tolerated, both as a monotherapy or in combination with ruxolitinib. One ruxolitinib-resistant or -intolerant patient discontinued due to serious adverse event(s), which were reported as unlikely related to CPI-0610. No JAK-inhibitor-naïve patients discontinued due to adverse events. Please review the abstracts here for more details.
The Company will present updates of clinical data from MANIFEST in oral and poster presentations at the ASH (Free ASH Whitepaper) annual meeting on December 9 and will also host an investor meeting. Please read here for additional information.
We expanded Arm 3 of MANIFEST for JAK-inhibitor-naïve patients from 43 to up to approximately 100 patients. We expanded Cohort 2A for TD ruxolitinib-refractory or -intolerant patients being treated with CPI-0610 + ruxolitinib, and we may expand Cohort 1A for TD ruxolitinib-refractory or -intolerant patients being treated with CPI-0610 monotherapy, from 16 to up to approximately 60 patients in each cohort.
We have started planning for a potential pivotal trial with CPI-0610 for MF in the first-line setting, and we expect the trial to begin in 2020.
CPI-1205
Constellation provided a program update on CPI-1205:
Enrollment in the Phase 2 portion of ProSTAR is nearly complete.
An endpoint accepted by regulatory authorities for pivotal clinical trials in prostate cancer is radiographic progression-free survival (rPFS). In addition, we learned from a study presented by the Kim Chi lab at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting that median responses to second-line therapy generally last only a few months.
Data from the Phase 1b portion of ProSTAR provided preliminary evidence of deep and durable effects of CPI-1205 in certain metastatic castration-resistant prostate cancer patients. We are shifting our focus in this study to durability of clinical activity with CPI-1205.
We are gathering data on time to progression (TTP) of CPI-1205 in ProSTAR, a metric that may serve as a surrogate for rPFS and may guide future development of the compound. Determining TTP will require additional time for the data set to mature, and we expect to report these data from ProSTAR in mid-2020. Plans for any potential Phase 3 program for CPI-1205 will depend on our assessment of the Phase 2 data.
CPI-0209
Enrollment of patients in a Phase 1/2 clinical trial of CPI-0209 continues according to plan. Dosing began in September 2019.
CPI-0209 is a second-generation and potentially best-in-class EZH2 inhibitor that has been designed to achieve comprehensive target coverage through extended on-target residence time. The compound has demonstrated more robust anti-tumor activity compared to first-generation EZH2 inhibitors in preclinical models of multiple cancer types. We believe that CPI-0209 may enable us to address additional patient populations beyond those that we are targeting with CPI-1205 or that have been targeted by other EZH2 inhibitors.
Third Quarter 2019 Financial Results
Cash, cash equivalents, and marketable securities as of September 30, 2019, were $89.1 million, a decline of 22.3% compared to December 31, 2018, primarily due to operating expenses. On October 3, 2019, the Company raised gross proceeds of $65 million in a private placement of its stock.
Research and development (R&D) expenses increased 27.6% year over year to $16.2 million in the third quarter of 2019 mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 30.7% year over year to $4.8 million in the third quarter of 2019, primarily due to building out the organization of the company.
The net loss increased 32.7% year over year to $21.1 million for the third quarter of 2019, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased 1.2% to $0.82 per share due to the increased net loss, offset in part by an increase in shares outstanding as a result of the initial public offering in 2018 and conversion of preferred stock to common stock.
Nine Month 2019 Financial Results
Research and development (R&D) expenses increased 48.9% year over year to $47.9 million in the first nine months of 2019, mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 66.8% year over year to $14.1 million in the first nine months of 2019, primarily due to building out the organization of the company.
The net loss increased 53.4% year over year to $61.3 million for the first nine months of 2019, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased 56.3% to $2.38 per share due to an increase in shares outstanding as a result of the initial public offering in 2018 and conversion of preferred stock to common stock.
Financial Guidance
Constellation expects that its cash, cash equivalents, and marketable securities as of September 30, 2019, plus the $65 million of proceeds from a private placement completed on October 3, 2019, will enable the Company to fund planned operating expenses and capital expenditure requirements into the first half of 2021.