Bexmarilimab Safe and Efficacious in Treating Myelodysplastic Syndromes, With Amer Zeidan, MD

Bexmarilimab has shown encouraging activity in patients with mutated tumor protein 53 (mTP53) high-risk myelodysplastic syndromes (MDS) when combined with azacitidine, with translational data supporting its potential for altering the immune dysregulation common in mTP53 MDS.1

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, by Amer Zeidan, MD, professor of medicine and chief of the Division of Hematologic Malignancies at Yale University, these data from the ongoing BEXMAB phase 1/2 study highlight a major step towards a potential therapy for a historically underserved disease population.1

“The combination was generally well-tolerated,” Zeidan told HCPLive in an exclusive interview. “In terms of the efficacy, we have seen encouraging efficacy in the relapsed/refractory setting: we saw responses with transfusion dependence, and importantly, the overall survival was in the range of 14.5 months, which is much better than an indirect comparison to what you typically see with HMA failure.”

Bexmarilimab is a novel macrophage checkpoint inhibitor targeting Clever-1, a scavenger receptor expressed on malignant blasts and monocytes in MDS bone marrow. TP53 is mutated in 5-10% of de novo and 30-40% of therapy-related MDS and is a frequent molecular abnormality in higher-risk MDS. Although hypomethylating (HMA) agents like azacitidine are standard of care for mTP53 MDS, higher-risk MDS is associated with shorter responses, inferior median overall survival, and high rates of relapse even after stem cell transplant.1

BEXMAB is a multicenter phase 1/2 open-label study assessing the safety, tolerability, and preliminary efficacy of increasing doses of bexmarilimab in patients with intermediate, high, or very high-risk MDS. Phase 1 of the study identified tolerable bexmarilimab doses among 4 levels via a Bayesian optimal interval dose escalation design, while phase 2 was an expansion to evaluate the safety and efficacy of bexmarilimab combined with standard of care. Both phases consisted of a screening period, a treatment period, and an end-of-treatment safety follow-up and progression/survival follow-up.2

For inclusion, patients were required to be ≥18 years with 1 of the following conditions:

• Morphologically confirmed MDS diagnosis with revised International Prognostic Scoring System (rIPSS) risk categories of intermediate, high, and very high
• Morphologically confirmed CMML-2 diagnosis with indication for azacitidine treatment
• CMML and MDS with response failure to HMA
• Morphologically confirmed diagnosis of r/r AML following ≥1 line of prior therapies with indication for azacitidine treatment
• Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment.

Patients were excluded if they exhibited acute promyelocytic leukemia or myeloproliferative CMML, autoimmune disorders, or a history of chronic ulcers or clinically relevant liver disease, among other conditions.2

A total of 21 treatment-naïve and 32 HMA r/r MDS patients have been recruited into BEXMAB – bexmarilimab 1-6 mg/kg in phase 1 and 3 or 6 mg/kg in phase 2 was administered weekly in 28-day cycles in combination with a standard regimen of azacitidine. Preliminary overall response rates (ORR) with bexmarilimab and azacitidine in treatment-naïve patients were 78% in mTP53 (biallelic ORR: 83%) and 91% in wt TP53. In r/r MDS, preliminary ORR were 46% in mTP53 (biallelic ORR: 38%) and 74% in wt TP53.2

“Of course, the numbers are somewhat small with limited follow-up, but I think that the data so far is encouraging,” Zeidan said. “The study is still ongoing; we still have ongoing follow-up of patients and hopefully we will be reporting additional results in the future.”

Editor’s Note: Zeidan reports disclosures with Bristol Myers Squibb, AbbVie, Amgen, Novartis, Pfizer, Takeda, and others.

References

1. Zeidan A, Stein A, Rimpiläinen J, et al. Efficacy, molecular and transitional analysis of TP53-mutated HR-MDS with bexmarilimab and azacitidine: Updated results from the BEXMAB phase 1/2 study. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Faron Pharmaceuticals Ltd. A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies (BEXMAB). ClinicalTrials.gov Identifier: NCT05428969. Updated December 1, 2025. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT05428969