Study highlights:

• Tissuemicroenvironments showed three distinct response patterns to bexmarilimab, driven by the level of inflammation, macrophage type, and their location within the tissue.
• Bexmarilimab stimulated response in immunologically-cold tumors and inhibited inflammation in treatment resistant tumors.
• New patent filed around gene signature validated to predict bexmarilimab sensitivity, offering a tool for patient selection.
• Cancer-free adjacent tissues also responded to bexmarilimab, primarily through B cell activation, hinting towards long lasting systemic beneficial affects against cancer.

Turku, Finland – Faron Pharmaceuticals Ltd. (AIM: FARN, First North: FARON), a clinical-stage biopharmaceutical company, today announced the publication of a new study in the peer-reviewed Journal for ImmunoTherapy of Cancer, shedding new light on how the tumor microenvironment (TME) influences the response to bexmarilimab, the company’s investigational macrophage-targeting immunotherapy.

The study, conducted by researchers at the University of Turku and Turku University Hospital, used advanced patient-derived explant culture (PDEC) models and cutting-edge transcriptomic profiling to map the immunological landscape surrounding tumors and their adjacent tissues. It identified critical molecular and cellular factors that determine how patients respond to bexmarilimab therapy.

Dr. Maija Hollmén, Chief Scientific Officer of Faron Pharmaceuticals and senior author of the study from MediCity Research Laboratory and InFLAMES Flagship, University of Turku, Finland, said, “This work gives us a mechanistic framework for understanding why some patients respond remarkably well to bexmarilimab while others do not in solid tumors. By recognizing that macrophage response is governed by the tissue’s immunological state, we open new possibilities for tailored therapy. This could help guide both clinical trial design and eventual treatment decisions, ensuring patients are matched with the right therapy to have a better chance at survival.”

Tumor-associated macrophages, or TAMs, are specific immune cells found within and around solid tumors. Depending on their type, they can either help the body fight cancer (immunostimulatory) or protect the tumor (immunosuppressive) and help it grow. Hence, it is important to study them in the tumor microenvironment (TME or the area around the tumor where these cells are present). By understanding how TAMs behave in different tumors, researchers can find better ways to treat cancer with medicines that reprogram these cells to attack the tumor instead of helping it. Bexmarilimab is a first-in-class humanized anti–Clever-1 antibody designed to reprogram TAMs from an immunosuppressive to an immunostimulatory phenotype. By inhibiting the scavenger receptor Clever-1, bexmarilimab enhances antigen presentation and promotes anti-tumor immunity. This study addresses the heterogeneity of TAMs by showing how their type, origin, and the tumor environment influence response to therapy.

Researchers analyzed samples of tumor and adjacent cancer-free tissue from patients with breast cancer who underwent mastectomy (PDEC model). They also applied a combination of single-cell RNA sequencing, spatial transcriptomics, and cytokine profiling to identify the genes associated with bexmarilimab’s response.

Bexmarilimab stimulated response in immunologically “cold” tumors (low inflammation) and reduced inflammation in TMEs with strong IFN signaling and advanced TAM activity. The analysis validated five genes (including CXCL9, FCGR1A, GBP5, SLAMF7, and SERPING1) that accurately predicted sensitivity to bexmarilimab. This allows for a potential biomarker-based strategy to enrich patient populations in clinical trials in solid tumors and optimize therapeutic outcomes. A new patent application has been filed for using this method for patient selection.

Dr. Petri Bono, Chief Medical Officer, Faron Pharmaceuticals, said, “As the immunotherapy landscape evolves, understanding the TME’s influence on treatment response is becoming increasingly critical. These findings lay a scientific foundation for advancing macrophage-targeting therapies beyond trial-and-error toward a more predictive treatment. It can potentially impact the design of future trials for bexmarilimab in solid tumors, including potential companion diagnostics based on the identified gene signature.”

Moreover, despite that macrophage are known to be crucial for innate immune responses cancer-free adjacent tissues consistently showed B cell activation regardless of the corresponding tumor’s response, hinting at systemic immune benefits as a part of adaptive immunity, i.e. the memory side of the immune system. These findings underscore the context-dependent nature of macrophage reprogramming and the need for precise patient selection in clinical development.

The study also highlighted that bexmarilimab may complement existing immune checkpoint therapies. Bexmarilimab targeted tumor environments that are immunologically opposite to those responsive to anti-PD-(L)1 therapy. While each associated differently with baseline IFN signaling, both triggered IFN responses when effective.

For the latest findings in Finnish, see the University of Turku press release.

Bexmarilimab is currently under investigation for both hematological cancers and advanced solid tumors. The ongoing BEXMAB clinical study is 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.

Faron will be hosting a virtual webinar to discuss the full analysis of r/r MDS as well as new frontline HR MDS patient data on Monday, 2 June 2025. To register for the event visit: BEXMAB Phase II study results

For more information, please contact:

About BEXMAB
The BEXMAB study is an open-label Phase I/II clinical trial investigating bexmarilimab in combination with standard of care (SoC) in the aggressive hematological malignancies of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary objective is to determine the safety and tolerability of bexmarilimab in combination with SoC (azacitidine) treatment. Directly targeting Clever-1 could limit the replication capacity of cancer cells, increase antigen presentation, ignite an immune response, and allow current treatments to be more effective. Clever-1 is highly expressed in both AML and MDS and associated with therapy resistance, limited T cell activation and poor outcomes.

About bexmarilimab
Bexmarilimab is Faron’s wholly owned, investigational immunotherapy designed to overcome resistance to existing treatments and optimize clinical outcomes, by targeting myeloid cell function and igniting the immune system. Bexmarilimab binds to Clever-1, an immunosuppressive receptor found on macrophages leading to tumor growth and metastases (i.e. helps cancer evade the immune system). By targeting the Clever-1 receptor on macrophages, bexmarilimab alters the tumor microenvironment, reprogramming macrophages from an immunosuppressive (M2) state to an immunostimulatory (M1) one, upregulating interferon production and priming the immune system to attack tumors and sensitizing cancer cells to standard of care.

About Faron Pharmaceuticals Ltd
Faron (AIM: FARN, First North: FARON) is a global, clinical-stage biopharmaceutical company, focused on tackling cancers via novel immunotherapies. Its mission is to bring the promise of immunotherapy to a broader population by uncovering novel ways to control and harness the power of the immune system. The Company’s lead asset is bexmarilimab, a novel anti-Clever-1 humanized antibody, with the potential to remove immunosuppression of cancers through reprogramming myeloid cell function. Bexmarilimab is being investigated in Phase I/II clinical trials as a potential therapy for patients with hematological cancers in combination with other standard treatments. Further information is available at www.faron.com