Evidence map›Paper›PMID 40369178›Full record

ArticleScientific reports2025

CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies.

Sofia Aakko, Arno Ylitalo, Heikki Kuusanmäki, Jenna H Rannikko, Mari Björkman, Jami Mandelin, Caroline A Heckman, Mika Kontro, Maija Hollmén

Registry-linked trialAbstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05428969 (A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of the Clever-1 Antibody Bexmarilimab in Combination With Standard of Care Therapy in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05428969 phase1 / phase2active not recruitingnot on this map

A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of the Clever-1 Antibody Bexmarilimab in Combination With Standard of Care Therapy in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia

TypeinterventionalSponsorFaron Pharmaceuticals LtdRan2022 to 2027Enrolled181ConditionsAcute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Relapsed/Refractory AMLArmsBexmarilimab, Azacitidine, Venetoclax
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Sofia AakkoFaron Pharmaceuticals Ltd, Turku, Finland.
Arno YlitaloMediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, Finland.
Heikki KuusanmäkiInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
Jenna H RannikkoMediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, Finland.
Mari BjörkmanFaron Pharmaceuticals Ltd, Turku, Finland.
Jami MandelinFaron Pharmaceuticals Ltd, Turku, Finland.
Caroline A HeckmanInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
Mika KontroInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
Maija HollménFaron Pharmaceuticals Ltd, Turku, Finland. maijal@utu.fi.

Funding

Business Finland 8040/31/2019
6 · The paper itself

Abstract

Treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) requires new therapy options, especially for patients uneligible for intense chemotherapy or with relapsed or refractory disease. CLEVER-1 is a myeloid checkpoint protein, which can be targeted with a therapeutic function blocking antibody, bexmarilimab. Bexmarilimab has shown clinical efficacy in different solid tumors. Here, we show preclinical data demonstrating expression of CLEVER-1 on immature malignant myeloid cells and their derivates in MDS and AML bone marrow samples and AML cell lines. Highest CLEVER-1 levels were observed in AML with monocytic differentiation. Ex vivo treatment of AML/MDS bone marrow samples with bexmarilimab led to an increase in antigen-presenting human leukocyte antigen DR isotype (HLA-DR) molecule expression. Combination of bexmarilimab with current standard-of-care (SoC) drugs, azacitidine and venetoclax, showed potential for HLA-DR induction and enhanced killing of leukemic cells, respectively. Our non-clinical findings support the feasibility of CLEVER-1 inhibition in AML/MDS to induce antigen presentating molecule expression and potentially, an anti-leukemic effect together with SoC. Therapeutic targeting of CLEVER-1 with bexmarilimab is currently undergoing clinical investigation in the BEXMAB trial (NCT05428969).

Indexed as

Antibodies, Monoclonal, HumanizedAzacitidineBridged Bicyclo Compounds, HeterocyclicHLA-DR AntigensLeukemia, Myeloid, AcuteMyelodysplastic SyndromesSulfonamidesCell Line, TumorClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicHumansMulticenter Studies as TopicAntibodies, Monoclonal, HumanizedAzacitidinebexmarilimabBridged Bicyclo Compounds, HeterocyclicHLA-DR AntigensSulfonamidesvenetoclaxAcute myeloid leukemiaBexmarilimabCLEVER-1ImmunotherapyMyelodysplastic syndromeStabilin-1

Identifiers

PMID40369178
PMCPMC12078569

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.