Constellation Pharmaceuticals Provides Update of Preliminary Data for CPI-0610 in Three EHA Abstracts

• Continued high rate of SVR35 in 1L patients: 72% at 12 weeks and 67% at 24 weeks
  
• SVR35 responses and transfusion dependence conversion observed in 2L monotherapy patients
• Improvement in bone marrow fibrosis seen across treatment arms
• Additional data to be presented at EHA from ~50 1L and 70-80 2L patients

CAMBRIDGE, Mass., May 14, 2020 (GLOBE NEWSWIRE) -- Constellation Pharmaceuticals, Inc. CNST today announced that three abstracts relating to the MANIFEST clinical trial of CPI-0610 in myelofibrosis were published online in association with the European Hematology Association (EHA) annual meeting. The abstracts include an analysis of data from 157 patients based on a data cutoff of January 9, 2020. An upcoming presentation of posters at EHA on June 12 will reflect an analysis of a larger patient population based on a later data cutoff. Constellation expects to present 12-week data in about 50 first-line patients and 24-week data in 25-30 first-line patients and 70-80 second-line patients at the EHA meeting. 

"The data from the abstracts include 35% reductions in spleen volume (SVR35), 50% improvement in Total Symptom Scores (TSS50), hemoglobin improvements, conversions to transfusion independence in transfusion-dependent (TD) patients, and bone marrow fibrosis improvements," said Claire Harrison, D.M., Professor of Haematology, and Clinical Director, Guy's and St Thomas' NHS Foundation Trust, and a MANIFEST investigator. "Evidence of clinical activity was seen both as monotherapy and in combination with ruxolitinib. If these preliminary data are confirmed in further testing, CPI-0610 may have the potential for disease modification and could become part of a new standard of care in myelofibrosis."

Data Highlights

Arm 3 (1L) – CPI-0610 + ruxolitinib in JAK-inhibitor-naïve patients

• 21 of 29 evaluable patients (72%) achieved SVR35 at 12 weeks
• Of 15 patients evaluable for SVR at week 24, 14 completed 24 weeks of treatment (one discontinued), with 10 patients (67%) achieving SVR35
• The median spleen volume change in those 14 patients was 54% at 24 weeks
• TSS50 responses at 12 and 24 weeks were 56% (15 of 27 evaluable patients) and 79% (11 of 14 evaluable patients), respectively
• 5 of 11 (46%) patients evaluable for bone marrow fibrosis had a >1 grade improvement at 24 weeks

Arm 1 (2L) – CPI-0610 monotherapy in JAK-inhibitor-experienced or -ineligible patients

• 2 of 10 (20%) and 4 of 11 (36%) evaluable non-transfusion-dependent (non-TD) patients achieved SVR35 (the primary endpoint for cohort 1B) and TSS50, respectively, at 24 weeks
• 3 of 10 (30%) evaluable non-TD patients had a >1 grade improvement in bone marrow fibrosis at 24 weeks
• 13 of 22 (59%) evaluable non-TD patients had > 1.5 g/dL increase in hemoglobin
• 2 of 6 (33%) evaluable TD patients converted to transfusion independence (the primary endpoint for cohort 1A)
• No evaluable TD patients achieved SVR35 or TSS50 at 24 weeks

Arm 2 (2L) – CPI-0610 + ruxolitinib in ruxolitinib-experienced patients

• 7 of 19 (37%) evaluable TD patients converted to TI (the primary endpoint for cohort 2A)
• 3 of 18 (17%) and 10 of 18 (56%) evaluable TD patients achieved SVR35 and TSS50, respectively, at 24 weeks
• 9 of 14 (64%) evaluable TD patients had a > 1 grade improvement in bone marrow fibrosis at 24 weeks
• No evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 2B) and 4 of 13 (31%) evaluable non-TD patients achieved TSS50 at 24 weeks

Safety

CPI-0610 in MANIFEST, both as monotherapy and in combination with ruxolitinib and in both JAK-inhibitor-naïve and JAK-inhibitor-experienced and -ineligible patients, was generally well tolerated.

Among the most common treatment-emergent adverse events (AEs) for CPI-0610 monotherapy in 43 safety-evaluable patients in Arm 1, those that were ≥ Grade 3 were thrombocytopenia (14.0%), anemia (7.0%), and diarrhea (4.7%). Two patients discontinued treatment because of AEs (blood creatinine increase, fatigue, and pleuritic pain). There were no Grade 5 AEs.

Among the most common treatment-emergent AEs in 61 safety-evaluable patients in Arm 2, those that were ≥ Grade 3 were thrombocytopenia (21.3%), anemia (8.2%), diarrhea (4.9%), infections (4.9%), nausea (1.6%), abdominal pain (1.6%), and vomiting (1.6%). Seven patients discontinued treatment due to AEs, including three previously reported Grade 5 AEs.

Among the most common treatment-emergent AEs in 53 safety-evaluable patients in Arm 3, those that were ≥ Grade 3 were anemia (15.1%), thrombocytopenia (5.7%), infections (3.8%), and dyspnea (3.8%). Two patients discontinued treatment due to AEs (infections); one of them was Grade 5 within 30 days of treatment discontinuation.

For further details, please see the EHA abstracts in the Investors and Media/Other Presentations section of Constellation's website, http://ir.constellationpharma.com/.

EHA Poster Presentations

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, in Combination with Ruxolitinib, in JAK Inhibitor Treatment Naive Myelofibrosis Patients: Update of MANIFEST Phase 2 Study (Submission ID: EHA-2731, Final Abstract Code: EP1084)

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 (Submission ID: EHA-3245, Final Abstract Code: EP1091)

TITLE: CPI-0610, Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as "Add-on" to Ruxolitinib (Rux), in Advanced Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST Phase 2 Study (Submission ID: EHA-2790, Final Abstract Code: EP1083)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

Investor Event

Constellation will host a virtual investor meeting and conference call to discuss these interim data on June 12. Details will be announced later.

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 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 CPI-0610 for the treatment of myelofibrosis as well as the EZH2 inhibitors CPI-1205 and CPI-0209 for the treatment of metastatic castration-resistant prostate cancer and other cancers. 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 implications of preliminary or interim clinical data, Company's plans, strategies and prospects for its business and statements regarding the development status of the Company's product candidates. 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 CPI-0610, CPI-1205 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 the substantial 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 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, including the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2020. 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.

Contact

Kia Khaleghpour, Ph.D.
Vice President, Investor Relations and Communications
Constellation Pharmaceuticals
+1 617-844-6859
kia.khaleghpour@constellationpharma.com

Ronald Aldridge
Senior Director, Investor Relations
Constellation Pharmaceuticals
+1 617-714-0539
ron.aldridge@constellationpharma.com

Lauren Arnold
Media Relations
MacDougall Biomedical Communications
+1 781-235-3060
larnold@macbiocom.com