Rethinking MDS: Starting with the immune system rather than the cancer cell 

Dear reader,

September is Blood Cancer Awareness Month. I want to use it to write about a disease that most people have never heard of, and about the question that has guided our work for the past several years.

Myelodysplastic Syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. Low blood cell counts, referred to as cytopenias, are a hallmark feature of MDS and are responsible for many of the symptoms that MDS patients experience — infections, fatigue, shortness of breath, anemia, spontaneous bleedings, or easy bruising.

Higher-risk myelodysplastic syndrome, HR-MDS, is the more aggressive form of MDS and characterized by high rates of treatment resistance and poor outcomes. Patients are typically older, often already weakened by their disease, and continue to face limited treatment options despite more than two decades of clinical progress in the field. The hypomethylating agent azacitidine has remained a backbone of higher-risk MDS treatment ever since its approval in 2004. Numerous randomized Phase 3 attempts to improve on it have failed. Not because the field has lacked effort, but because the disease itself is genuinely challenging.

What makes HR-MDS so resistant? The answer, I think, starts with where most drug development has been looking. The prevailing logic in oncology, to kill more cancer cells more effectively, has produced extraordinary results in many tumor types. In HR-MDS, it has repeatedly hit a wall. Combinations involving BCL-2 inhibition generated considerable early enthusiasm in HR-MDS but have thus far failed to improve outcomes in later randomized studies. CD47-targeting antibodies also generated early excitement, but those promising early observations did not ultimately translate into successful late-stage development programs. In several cases, the single-arm combination data looked more promising than the results ultimately seen in randomized later-stage clinical studies.

At some point, that pattern stops looking like bad luck and starts looking like information. The information, in this case, is that simply killing more cancer cells may not be enough for this disease.

The question we have been pursuing at Faron is different. Rather than asking how to kill more malignant cells, we asked: why is the immune system failing to do what it is supposed to do? Increasing evidence suggests that HR-MDS is shaped not only by the malignant cells themselves, but also by the bone marrow environment in which they live. In higher-risk disease, that environment becomes profoundly immunosuppressive. Macrophages, immune cells that normally help recognize threats and coordinate the body’s response to them, appear to be co-opted by the disease. Instead of helping to activate an immune response, they can contribute to suppressing it. The cancer has effectively hijacked the sentinels.

Clever-1 is a receptor expressed on the surface of these immunosuppressive macrophages. Targeting it with bexmarilimab reprograms them. Not kills them, reprograms them. From a state that protects the tumor to one that supports an anti-tumor immune response. What this may mean clinically, and what we have begun to observe in the BEXMAB trial, is not only anti-tumor activity but also evidence that bone marrow function may be improving, including signs of tri-lineage hematopoietic recovery. Rather than directly targeting malignant cells, this approach seeks to restore immune function within the bone marrow microenvironment. Most therapies that have reached late-stage development in HR-MDS have focused on directly impairing malignant cells. Bexmarilimab starts from a different premise: that reactivating the immune system may be just as important as attacking the malignant population itself.

Very importantly, this is the question that has guided the past several years of our work. Not every drug development program that asks a different question succeeds. But I think the clinical and biological evidence we have accumulated gives us genuine reason to believe we are targeting an important piece of the core biology that drives this disease.

Next week, our Medical Director Aneel Nimba will go deeper into what that evidence looks like in practice, specifically what the data we presented at EHA in June 2026 actually showed, and why the translational results from inside the bone marrow matter as much as the response rates. I hope you’ll follow along.

— Petri Bono, Chief Medical Officer

Forward-looking statements: This post contains forward-looking statements regarding the development of bexmarilimab. Bexmarilimab is investigational and has not been approved by any regulatory authority.