Shots:
- Myelodysplastic Syndrome (MDS) is a rare and aggressive blood cancer in which the bone marrow fails to produce enough healthy blood cells
- As resistance to traditional treatments continues to rise among MDS patients, Faron Pharmaceuticals’ Bexmab emerges as a promising alternative
- Dr. Petri Bono, Chief Medical Officer at Faron Pharmaceuticals, highlights Bexmab’s unique mechanism of action and shares encouraging Phase II data.
Saurabh: What specific structural or functional properties of Clever-1 make it a tractable target for reversing immunosuppression in HR-MDS? How does its overexpression correlate with therapy resistance?
Petri: CLEVER-1 (also known as Stabilin-1) is a receptor found in abundance on certain immune-suppressing macrophages and on cancerous myeloid cells in conditions like high-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukemia (AML). Its main role is to help clear away damaged fats and dead cells, which in turn keeps the environment around the tumor calm and anti-inflammatory. This ‘quiet’ environment makes it harder for the immune system to mount an effective response and is linked to resistance to standard treatments in HR-MDS.
Bexmarilimab, a humanized IgG4 monoclonal antibody, is designed to block CLEVER-1 and disrupt this immunosuppressive effect. By binding to CLEVER-1, bexmarilimab switches immune cells from a ‘quiet’ mode to an active, pro-inflammatory state, improving their ability to present antigens and stimulate T cells. It also enhances the immune system’s ability to recognize and target cancer cells. In preclinical studies, bexmarilimab has been shown to increase expression of key immune markers (like HLA-DR) on malignant cells and make them more responsive to commonly used treatments such as azacitidine and venetoclax. These findings support CLEVER-1 as a valuable target for tackling immune resistance in HR-MDS and improving patient outcomes.
Saurabh: What differentiates Bexmarilimab as a treatment option for higher-risk myelodysplastic syndrome (HR-MDS), and how does it stand out compared to existing therapies?
Petri: High-risk myelodysplastic syndromes (HR-MDS) remain one of the most difficult blood cancers to treat, with current standard-of-care options offering limited success. Supportive care such as blood transfusions and antibiotics helps manage symptoms but does not alter the course of the disease. While stem cell transplant is the only curative option, it is not feasible for most patients due to age, comorbidities, or donor limitations.
Treatment of AML and MDS is often difficult because of treatment resistance. Bexmarilimab helps overcome this by dual mode of action i.e. by reactivating the immune system at its core (i.e., macrophages) and by targeting the CLEVER-1 protein found on the leukemic cells. It reprograms tumor-associated macrophages (TAMs) to overcome immune suppression and sensitizes the leukemic blast cells back to standard of care treatment. This offers a new and much-needed treatment option for patients with these hard-to-treat blood cancers. It can be combined with standard-of-care therapies and has shown responses in patients who have failed prior HMA therapy (relapsed/refractory MDS or r/r MDS).
The recent phase II data is a part of oral presentations at ASCO and EHA 2025.
Key highlights from the ongoing clinical trial
- In the Bexmab Phase 1 & 2 trial, patients with r/r MDS experienced an estimated median overall survival (mOS) of approximately 13.4 months, compared to the 5-6 months that would typically be expected with standard-of-care drugs.
- The topline phase II Bexmab data showed a high objective response rate (ORR) of 63% in r/r HR-MDS and 76% in treatment naïve (frontline) HR MDS patients.
- Bexmarilimab was found to be safe and effective, leading to improvements in blood values and this way also to a better quality of life for patients
Saurabh: How do the Phase II results, particularly the 63% overall response rate in relapsed/refractory HR-MDS patients, compare to existing treatment options, and what impact could this have on the current treatment landscape?
Petri: The mainstay treatments for patients with r/r HR-MDS include hypomethylating agents (HMAs) like azacitidine and decitabine and offer only modest benefits. Up to 50% of patients do not respond at all, and even among those who do, almost all relapse within 1 to 2 years. After HMA failure, survival drops sharply, with median survival just 5–6 months. Options at that point are extremely limited, often involving another HMA, chemotherapy, or enrolment in a clinical trial. This underscores the urgent need for innovative therapies that go beyond symptom control to meaningfully improve survival and quality of life of these patients.
In contrast, Phase II data from the Bexmab study showed a 63% overall response rate in this population. Moreover, the treatment continues to be well tolerated without any dose-limiting toxicities. In the phase I/II Bexmab data on r/r MDS presented at MDS 2025, a reduction of 50% or more in bone marrow blast counts was observed in 55% of patients, indicating clinically significant disease control. Additionally, 21% of patients who were transfusion dependent at baseline achieved transfusion independence, reflecting a potential improvement in quality of life and a reduced need for supportive care. Importantly, four patients were able to proceed to hematopoietic stem cell transplantation, suggesting that this regimen may serve as an effective bridge to transplant. This efficacy, especially in this difficult to treat population, positions bexmarilimab as a viable option for patients with r/r MDS where few alternatives exist.
Saurabh: How do the response rates differ between frontline (treatment-naïve) HR-MDS patients and those with relapsed/refractory disease, and what might explain these differences?
Petri: Preliminary Bexmab data indicate that both frontline and relapsed/refractory HR-MDS patients can respond to bexmarilimab, with higher response rates seen in the treatment-naïve population. Recent translational research shows that differences in tumor microenvironment (TME), tumor-associated macrophage composition, Clever-1 expression, and inflammation may explain the varied responses. Detailed breakdowns are expected in upcoming full data presentations.
Saurabh: What can you tell us about the safety profile observed in the Bexmab Phase II trial, especially regarding tolerability and the absence of dose-limiting toxicities?
Petri: Bexmarilimab has been well tolerated across more than 200 patients treated to date. In the Bexmab Phase II trial, there were no dose-limiting toxicities attributed to the drug. The combination with azacitidine showed a favorable safety profile, with manageable side effects. Immune-related adverse events (common in currently approved checkpoint inhibitor treatments) were very rare, in less than 4% of the patients. This supports bexmarilimab’s potential for long-term use, especially in vulnerable HR-MDS populations.
Saurabh: The full Phase II data have been submitted to the 2025 ASCO Annual Meeting. What key efficacy and safety insights can be expected from the data presentation?
Petri: The ASCO 2025 presentation is expected to showcase updated data on overall response rates, safety outcomes, and survival in both frontline and relapsed/refractory cohorts.
Saurabh: What are the next steps in the clinical development plan, specifically regarding the planned Phase III trial and the timeline for FDA End of Phase II meeting feedback?
Petri: Faron has completed enrolment for the Phase II dose optimization cohort and plans to have an end of Phase II meeting with the FDA in summer 2025-, with feedback informing Phase III design and regulatory pathway.
About the Author:
Dr. Petri Bono
Dr. Petri Bono, M.D, Ph.D, is a seasoned senior pharmaceuticals executive with a background in oncology and various leadership positions.
Dr. Bono has participated in numerous oncology trials from Phase 1 to 3, including early phase immuno-oncological trials and published 102 peer reviewed papers in international journals including New England Journal of Medicine, Lancet Oncology, JAMA as well as Cancer Cell.
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