MorphoSys AG / Constellation Pharmaceuticals, Inc.

Myelofibrosis (BET inhibitor pelabresib) and EZH2-driven hematologic/solid tumors (CPI-0209)

18K US cases/yr · $2.4B Jakafi 2021 net product revenues (USD MM, Incyte 10-K) · 3000 US new myelofibrosis cases annually

Disease Overview

Myelofibrosis (MF) is a rare BCR-ABL-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, splenomegaly, cytopenias and constitutional symptoms (fatigue, night sweats, pruritus, weight loss), driven by JAK-STAT pathway dysregulation arising from JAK2 V617F (~50%), CALR (~30%) or MPL (~5-10%) mutations and amplified by inflammatory cytokine signaling. Median overall survival in intermediate-2/high-risk patients is roughly 4-7 years per DIPSS-Plus, with ~15-20% progressing to acute myeloid leukemia. US prevalence is approximately 16,000-18,500 with annual incidence of about 3,000 (NORD/MPN Research Foundation), making this an orphan oncology setting. Standard of care is JAK inhibition — ruxolitinib (Jakafi/Jakavi, Incyte/Novartis, FDA 2011), fedratinib (Inrebic, BMS, 2019), pacritinib (Vonjo, CTI BioPharma, 2022) and momelotinib (Ojjaara, GSK via Sierra Oncology, 2023) — but JAK monotherapy fails to address underlying clonal disease and produces incomplete spleen and symptom responses, leaving substantial unmet need for combination or disease-modifying mechanisms. Global myelofibrosis sales were ~$2.5-2.8B in 2021 (Jakafi alone $2.4B per Incyte 10-K), forecast to surpass $5B by 2030.

Competitive Landscape

At deal date (June 2021) pelabresib (CPI-0610) was the most advanced BET (bromodomain and extraterminal) inhibitor in clinical oncology, in Phase 3 MANIFEST-2 vs. ruxolitinib in JAK-inhibitor-naïve myelofibrosis, with positive Phase 2 MANIFEST data in JAKi-experienced patients. Competitive BET landscape: AbbVie/Genentech mivebresib (Phase 1, AML/solid tumors), Bayer BAY 1238097 (discontinued 2017), GSK molibresib (GSK525762, Phase 2 NMC and hematologic, deprioritized), Resverlogix apabetalone (Phase 3 BETonMACE in CV, missed 2019), Incyte INCB054329 (Phase 1, terminated). Adjacent myelofibrosis combinations included Sierra Oncology momelotinib (acquired by GSK Jun 2022 for $1.9B), CTI BioPharm pacritinib (FDA approval Feb 2022), Geron imetelstat (telomerase inhibitor, Phase 3 IMpactMF), Gilead/Forty Seven magrolimab (anti-CD47, Phase 2 with azacitidine, later discontinued in MDS Jul 2023), Celgene/BMS luspatercept (Reblozyl, anemia adjunct), Karyopharm selinexor (XPO1, Phase 3 SENTRY) and Telios/Sumitomo navtemadlin (KRT-232, MDM2). For EZH2 inhibitors paralleling CPI-0209 the competitive set includes Epizyme/Ipsen tazemetostat (Tazverik, FDA 2020 in epithelioid sarcoma and FL), Constellation's own first-gen CPI-1205, Daiichi Sankyo valemetostat (DS-3201, Phase 2 PTCL).