Faron Pharmaceuticals Limited (AIM:FARN) has unveiled new research identifying a secreted molecule that helps cancers evade the immune system, offering fresh insight into how its lead investigational therapy, bexmarilimab, could enhance responses to immunotherapy.
The study, published in the peer-reviewed journal Theranostics, identifies a soluble form of Clever-1, a receptor involved in immune suppression, as a key contributor to resistance against anti-PD-1 therapies, which are widely used in cancer treatment to activate the body’s T cells against tumours.
Clever-1 is typically found on the surface of macrophages, a type of white blood cell that can suppress immune responses.
The research, supported by Faron and funded by several institutions including Cancer Research UK and the University of Turku, found that a truncated, circulating form of this receptor, referred to as secreted Clever-1 or sClever-1, was enriched in the blood of cancer patients and actively suppressed immune activity.
The team showed that sClever-1 binds to activated T cells, interfering with their ability to attack tumours and promoting a more immunosuppressive environment. Patients with higher levels of sClever-1 were more likely to be resistant to anti-PD-1 checkpoint inhibitors, suggesting the molecule could serve as a biomarker to guide treatment decisions.
Bexmarilimab, Faron’s clinical-stage antibody targeting Clever-1, was found to significantly reduce sClever-1 levels in patients taking part in early trials.
The drop in sClever-1 was linked to improved T cell activity, supporting earlier observations that the therapy may help restore immune responses in otherwise resistant cancers.
Researchers also found that adding synthetic sClever-1 to tumour samples increased production of TGF-β, a known immune-dampening protein, reinforcing the molecule’s role in shielding cancer cells from attack.
“These unique findings further solidify our conviction in bexmarilimab's unique mechanism of action,” said Petri Bono, Faron’s chief medical officer.
“The ability of bexmarilimab to reduce systemic levels of the immunosuppressive sClever-1 provides a clear rationale for its potential to overcome immunotherapy resistance.
This adds to the growing body of evidence supporting bexmarilimab’s development as a potential cornerstone of immunotherapy for patients with aggressive cancers.
"This also provides a very intriguing basis of using soluble Clever-1 to inactivate T-cells in conditions where they are attacking our own body, i.e. in a wide range of auto-immune and inflammatory conditions”