Events

Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cytopenias, and a risk of progression to acute myeloid leukemia. Despite advances in understanding disease biology, the therapeutic landscape of high-risk MDS has remained largely stagnant. Azacitidine is still the only agent proven to prolong survival, with no new standard-of-care disease-modifying therapies approved for over 15 years. This therapeutic gap underscores the urgent need for innovative strategies to improve patient outcomes. 

Clever-1 is an immunosuppressive scavenger receptor expressed on monocytes, macrophages, and malignant blasts, contributing to immune evasion and disease persistence. Bexmarilimab, a first-in-class humanized antibody targeting Clever-1, is designed to address this axis through a dual mode of action. First, it reprograms immunosuppressive macrophages toward a pro-inflammatory, antigen-presenting phenotype capable of restoring antitumor T-cell responses. Second, it directly targets Clever-1–positive myeloid blasts, enhancing their recognition and clearance. 

Early clinical findings from the ongoing phase I/II BEXMAB trial have demonstrated that bexmarilimab is well tolerated and shows encouraging biological and clinical activity in patients with high-risk MDS. Importantly, evidence indicates that bexmarilimab can sensitize malignant cells to hypomethylating agents, thereby augmenting standard-of-care therapies. 

In this lecture, I will outline the rationale for targeting Clever-1, summarize recent translational and clinical results from the BEXMAB trial, and discuss the potential of bexmarilimab to redefine the therapeutic paradigm for high-risk MDS after more than a decade of limited progress. 

Relevat references from the speaker for this talk:

• Kontro M, Stein AS, Pyörälä M, Rimpiläinen J, Siitonen T, Ylitalo A, Fjällskog M-L, Jalkanen J, Aakko S, Pawlitzky I, Hollmén M, Daver N. Bexmarilimab plus azacitidine for higher-risk myelodysplastic syndrome and relapsed or refractory acute myeloid leukaemia: results from the dose-escalation part of the multi-centre, single-arm, phase I/II trial. Lancet Haematology. 2025; 12(7):e516-e528.  
• Aakko S, Ylitalo A, Kuusanmäki H, Rannikko JH, Björkman M, Mandelin J, Heckman CA, Kontro M, Hollmén M. CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies. Scientific Reports. 2025; 15, Article number: 16775. 
• Rannikko JH, Verlingue L ,de Miguel M, Pasanen A, Robbrecht D, Skyttä T, Iivanainen S, Shetty S, Ma YT, Graham DM, Arora SP, Jaakkola P, Yap C, Xiang Y, Mandelin J, Karvonen MK, Jalkanen J, Karaman S, Koivunen JP, Minchom A, Hollmén M, Bono P. Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: the phase I/II first-in-human MATINS trial. Cell Reports Medicine. 2023; 30:101307. 
• Hollmén M, Maksimow M, Rannikko JH, Karvonen MK, Vainio M, Jalkanen S, Jalkanen M, Mandelin J. Nonclinical characterization of bexmarilimab, a Clever-1-targeting antibody for supporting immune defense against cancers. Molecular Cancer Therepeutics. 2022; 21:1207-1218.   
• Hollmén M, Figueiredo CR, Jalkanen S. New tools to prevent cancer growth and spread: a ‘Clever’ approach. British Journal of Cancer. 2020; 123(4):501-509.