Faron’s Bexmarilimab demonstrates immune-activating and drug-sensitizing potential in myeloid malignancies

New preclinical data published in Scientific Reports confirms CLEVER-1 inhibition by Bexmarilimab increases antigen presentation and overcoming resistance to standard-of-care drugs

Study highlights:

Ex vivo treatment of AML and MDS bone marrow samples with bexmarilimab led to increased antigen-presenting human leukocyte antigen DR isotype (HLA-DR) expression, indicating improved antigen presentation capacity.

Bexmarilimab, when combined with azacitidine or venetoclax, enhanced HLA-DR expression and in many samples, reduced the viability of leukemic blasts, particularly in venetoclax-resistant samples.

The triple combination of bexmarilimab + azacitidine + venetoclax showed greater anti-leukemic effect in resistant AML cell lines than standard treatments alone.

Turku, Finland – Faron Pharmaceuticals Ltd. (AIM: FARN, First North: FARON), a clinical-stage biopharmaceutical company developing novel immunotherapies, today announced the publication of a new peer-reviewed preclinical study in Scientific Reports, validating the immune-reprogramming and anti-leukemic potential of its investigational macrophage CLEVER-1 inhibitor, bexmarilimab, in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

The study, conducted in collaboration with leading Finnish and Danish academic research centers, examined AML cell lines and bone marrow samples from patients with AML (n = 34) and MDS (n = 4) and showed that CLEVER-1 is highly expressed on malignant myeloid cells, especially in AML with monocytic differentiation.

Immunotherapy treatments have revolutionized the treatment of many cancers but remain largely ineffective in AML and MDS due to immune resistance. Bexmarilimab addresses these challenges by reactivating the immune environment at its source (i.e. macrophages) and targeting CLEVER-1 directly on leukemic blasts. This approach represents a novel therapeutic avenue in myeloid malignancies where effective treatments are urgently needed.

CLEVER-1, a scavenger receptor involved in immunosuppression, was found to be highly expressed on immature myeloid cells and their monocytic derivatives, particularly in AML cases with M4-M5 FAB subtypes and in Fms Related Receptor Tyrosine Kinase 3 (FLT3) and/or Nucleophosmin 1 (NPM1) mutations.

“Our results show that CLEVER-1 is not only a macrophage checkpoint but also expressed on malignant myeloid cells and targeting it with bexmarilimab can enhance antigen presentation and sensitize these cells to standard therapies. These findings highlight a compelling opportunity to integrate bexmarilimab into standard treatment regimens for AML and MDS,” said Dr. Maija Hollmén, Chief Scientific Officer of Faron and senior author of the study, MediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, Finland.

Using ex vivo models, the team evaluated the effects of bexmarilimab, alone and in combination with standard-of-care therapies azacitidine and venetoclax, on immune activation and cell viability. Bexmarilimab monotherapy increased the expression of antigen-presenting HLA-DR by 1.2- to 2-fold in up to 66% of patient samples, especially in those with low baseline expression and high CLEVER-1 levels, without any cytotoxic effects on the blast cells, via potentially inducing interferon gamma (IFNg). Addition of bexmarilimab helped overcome venetoclax-resistance in 33–40% of ex vivo AML samples, without adding to lymphocyte toxicity. Moreover, the triplet of bexmarilimab, azacitidine, and venetoclax showed enhanced cytotoxicity in ex vivo models of treatment-resistant AML; suggesting that bexmarilimab increases the susceptibility to venetoclax and/or azacitidine induced cell death.

“This is an important milestone in our mission to bring the benefits of macrophage checkpoint inhibition to patients with hematological cancers like AML and MDS, especially after disease relapse,” said Dr. Juho Jalkanen, CEO of Faron Pharmaceuticals. “The results strongly support the clinical rationale for combining bexmarilimab with standard therapies and also offer compelling evidence that our approach is both scientifically robust and clinically relevant, guiding the continued advancement of our BEXMAB trial.”

The ongoing BEXMAB clinical study is currently evaluating bexmarilimab in combination with azacitidine in relapsed/refractory AML and MDS patients. The trial’s most recent phase II data, to be presented at ASCO and EHA 2025, showed promising response rates in pretreated populations.

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