Trials for Myelodysplastic Syndrome: Genomics, Immunotherapy and Patient-Centric Design

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders marked by ineffective blood cell production, progressive cytopenias and the risk of transformation to acute leukemia. In the US, roughly 10,000 to 15,000 new cases are diagnosed each year (with an age-adjusted incidence of ~4.4–4.6 per 100,000).

MDS is primarily a disease of older adults: the median age at diagnosis is around 70 years, and incidence rises steeply with age, affecting more than 25 per 100,000 in populations older than 65. Prognosis remains poor: the observed three-year survival rate is about 42%, dropping to 29% at five years, depending on risk stratification.

Amid limited treatment options and high relapse rates, Faron Pharmaceuticals is advancing a novel investigational monoclonal antibody-based immunotherapy for MDS treatment that targets the tumor microenvironment rather than the cancer cells alone.

The investigational drug targets CLEVER-1, a scavenger receptor on macrophages that promotes immune suppression within the bone marrow. By blocking this receptor, the treatment reprograms macrophages into a pro-inflammatory state capable of supporting anti-tumor immune activity.

Faron’s lead candidate also aims to restore normal immune activation, strengthening T-cell responses and enabling the patient’s immune system to target malignant cells more effectively. It represents a promising new direction in the treatment of higher-risk MDS.

Dr. Petri Bono, Chief Medical Officer at Faron Pharmaceuticals, draws on decades of clinical and research experience to rethink how MDS is studied and treated. In our interview, he outlines how advances in genomics, immune microenvironment biology and smarter trial design are converging to redraw what’s possible in this challenging space.

Over the last ten years, MDS biology has moved from descriptive morphology to molecular precision. Dr. Bono attributes much of that shift to comprehensive genomic profiling and next-generation sequencing (NGS).

“These technologies have dramatically increased our understanding of the mutational landscape of the disease,” he explained.

NGS has identified recurring genetic mutations in MDS, helping researchers distinguish which mutations drive disease progression and which are incidental, and revealing how specific genetic changes influence clinical outcomes.

These molecular findings have been translated into practical clinical tools, including the 2022 IPSS-M (International Prognostic Scoring System-Molecular), an updated scoring system that incorporates genetic mutation data alongside traditional clinical and cytogenetic measures. Dr. Bono noted that precise baseline characterization using such models is essential for fair randomization and meaningful outcome interpretation in clinical trials.

“MDS has been shifting from a morphology- or cytogenetic-defined disease to a molecularly defined one.”

— Dr. Petri Bono

Another key advance is single-cell longitudinal sequencing, which allows researchers to observe clonal evolution and resistance mechanisms in real time. “It helps to understand better how clones expand and how these diseases actually progress,” Dr. Bono said.

Among the most critical discoveries is the behavior of TP53 mutations. Multi-hit, or biallelic, TP53 alterations define an especially aggressive patient subset with short-lived responses despite initial sensitivity to treatment. “In future trials, at least stratification, and perhaps even dedicated studies, for TP53-mutated MDS will be important,” he added.

Beyond genomics, scientists are uncovering the role of immune dysregulation within the bone-marrow microenvironment. Elevated inflammatory signaling and suppressive macrophage activity promote disease progression.

“Immune suppression is the reason these diseases can progress to a more malignant phenotype,” Dr. Bono said, noting that reprogramming macrophages toward a pro-inflammatory state could restore antitumor immunity.

Read Xtalks Clinical Edge™ Issue 6 Featuring Faron Pharmaceuticals and More

Xtalks Clinical Edge is a magazine for clinical research professionals and all who want to be informed about the latest trends and happenings in clinical trials. This magazine immerses you in a world where industry leaders, patient advocates and top researchers converge to provide the most insightful perspectives on clinical trials.