Constellation Pharmaceuticals Update on MANIFEST Clinical Trial of CPI-0610 in Myelofibrosis

CAMBRIDGE, Mass., Jan. 03, 2019 (GLOBE NEWSWIRE) – Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today provided an update on progress in the MANIFEST Phase 2 clinical trial of CPI-0610 in myelofibrosis (MF). The Company also reviewed its 2018 accomplishments and announced its data disclosure plans for 2019.

constellation pharmaceuticals MANIFEST clinical trial of CPI-0610 in myelofibrosisAs of December 10, 2018, each of the first four ruxolitinib-resistant second-line MF patients in MANIFEST remained on study. The two patients treated with a combination of CPI-0610 and ruxolitinib (i.e., CPI-0610 added onto existing treatment with ruxolitinib) have been treated for over 16 months. The two patients treated with CPI-0610 monotherapy have been treated for over 12 months. Each of the 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 our data cutoff, this patient’s response has persisted free of transfusions for over 52 weeks. Additionally, bone marrow biopsies before and after treatment were analyzed for the two patients on monotherapy, and both demonstrated a one-grade improvement in bone marrow fibrosis score as well as associated improvements in hemoglobin and platelets. Taken together, these results suggest that CPI-0610 may be modifying the underlying course of the disease in these ruxolitinib-resistant MF patients.

The Company has now opened 16 clinical trial sites in the U.S., Canada, and E.U. and enrolled 18 patients in MANIFEST. Only one patient has discontinued treatment, which was due to a non-drug-related serious adverse event. The recommended Phase 2 dose of CPI-0610 in the MANIFEST study is 125 mg once daily (may be titrated up), which is below the maximum tolerated dose of 225 mg once daily. Furthermore, in a Phase 1 clinical trial of CPI-0610, the Company also showed that the dose-limiting toxicity of thrombocytopenia was reversible and non-cumulative. Taken together, preliminary data suggest that CPI-0610 may have a wider therapeutic window and the potential for a differentiated toxicity profile relative to some other BET inhibitors, based on their published data.

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of the BET inhibitor CPI-0610 in patients with myelofibrosis (MF). MANIFEST is evaluating CPI-0610, either as a monotherapy or in combination with ruxolitinib, in patients with MF who are refractory to or intolerant of or have relapsed or lost response to the standard of care. Based on encouraging preliminary data, Constellation amended the design of each second-line cohort to stratify all patients enrolled in the study based on transfusion dependence status. In addition, the Company amended the design of MANIFEST to include a third cohort designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients.

A Look Ahead at 2019

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About David Wallace

Founder of PV Reporter, a resource for Myeloproliferative Neoplasm (MPN) patients and caregivers. After being diagnosed with Polycythemia Vera (PV) in 2009, I utilized social media to connect with "informed patients" and develop a better understanding of emerging treatment options. My philosophy on patient care is straight forward - "educating the patient is essential, so the patient can guide their physician to meet his or her needs." PV Reporter is a comprehensive resource hub giving visitors vital tools to become "empowered patients."

 
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