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An elderly man sitting on his porch laughing


What is Pelabresib?

Pelabresib (CPI-0610) is an investigational selective small-molecule designed to promote anti-tumor activity by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. The compound has demonstrated a wide therapeutic window, with activity seen at a 48 mg dose in a lymphoma study and with a maximum tolerated dose of 225 mg. Constellation Pharmaceuticals, a MorphoSys company, is using a starting dose of 125 mg in MANIFEST, our global, multicenter, open-label Phase 2 study of pelabresib in patients with Myelofibrosis (MF). Preclinical studies and translational insights from our first-in-human study of pelabresib led us to prioritize the clinical development of pelabresib in MF.


Phase II MANIFEST trial is testing pelabresib:


  • as monotherapy in MF patients who are refractory to or intolerant of/ineligible for, and are no longer on, ruxolitinib (Arm 1);
  • as add-on to ruxolitinib in MF patients who have had a suboptimal response to ruxolitinib or have experienced disease progression (Arm 2);
  • in combination with ruxolitinib in MF patients as 1L therapy who are JAK-inhibitor-naïve (Arm 3)
  • as monotherapy in patients with high-risk essential thrombocythemia who are intolerant of, or refractory to, hydroxyurea (Arm 4)


We have also initiated MANIFEST-2, a global, double-blind, randomized Phase 3 clinical study with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-naïve patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have splenomegaly and symptoms requiring therapy. We are randomizing patients to receive pelabresib + ruxolitinib or the placebo + ruxolitinib. The primary endpoint of the study is a ≥35% reduction in spleen volume (SVR35) from baseline at 24 weeks. A key secondary endpoint of the study is 50% or greater improvement in Total Symptom Score (TSS50) from baseline at 24 weeks. Other endpoints include bone marrow fibrosis grade improvements, duration of transfusion independence, rate of red-blood-cell transfusion for the first 24 weeks, and hemoglobin response.


If you are a US healthcare provider and would like to learn more about MANIFEST-2, click here



MANIFEST-2 is a global, randomized, double-blind, Phase 3 trial in adult patients with myelofibrosis who have not been previously treated with a JAK inhibitor. The purpose of the study is to evaluate the efficacy and safety of pelabresib, an oral BET inhibitor, plus ruxolitinib (a JAK inhibitor) compared with ruxolitinib alone.

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Disclaimer: MorphoSys’ product candidates are investigational and are currently not approved for the treatment of any disease or condition anywhere in the world. They cannot be prescribed or purchased for therapy at present. The MorphoSys website may contain information on drug candidates and clinical trials sponsored by MorphoSys with the intention of increasing the transparency of the company’s clinical research. There is no guarantee any product will be approved in the sought-after indication. Information contained within this website is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. All reasonable precautions have been taken to ensure the accuracy, security, and confidentiality of information available through the site. MorphoSys may amend the information at any time without notice.