On May 30, 2022 Faron Pharmaceuticals Ltd (AIM: FARN, First North: FARON), a clinical stage biopharmaceutical company focused on building the future of immunotherapy by harnessing the power of the immune system to tackle cancer and inflammation, reported that new biomarker data from patients treated with bexmarilimab as part of the ongoing phase I/II MATINS (Macrophage Antibody to Inhibit Immune Suppression) trial, will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting being held in Chicago, US from June 3 – 7 (Press release, Faron Pharmaceuticals, MAY 30, 2022, View Source [SID1234615233]). These data (Abstract #2645) will be featured in the "Developmental Therapeutics—Immunotherapy" session on Sunday, June 5, 2022 at 9:00 AM EDT.
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The MATINS trial is investigating the safety and efficacy of bexmarilimab as a monotherapy in patients with solid tumors who have exhausted all treatment options. Faron’s wholly-owned novel precision cancer immunotherapy targets Clever-1, a receptor known to be expressed on immunosuppressive macrophages in the tumor microenvironment. Bexmarilimab works by converting highly immunosuppressive M2 macrophages to immune stimulating M1 macrophages, which activates antigen presentation and promotes interferon gamma secretion by leukocytes. This can turn "cold" tumors into "hot" tumors; allowing the immune system to recognize and target cancer cells.
The biomarker analysis shows that the tumors of patients benefiting from bexmarilimab treatment expressed low levels of PD-L1 – a patient group that generally does not receive benefit from or is ineligible for treatment with currently approved checkpoint inhibitors. Median PD-L1 Combined Positive Score (CPS) was 1 (range 0-2) in patients that benefitted from bexmarilimab. The PD-L1 CPS score was 5 (range 0-100) for patients who did not benefit from bexmarilimab treatment. Further, the analysis showed that patients with higher levels of Clever-1 positive intra-tumoral cells were more likely to experience a clinical benefit when treated with bexmarilimab [15% vs 3%, respectively; p=0.038].
"While the arrival of currently available checkpoint inhibitors was, undoubtedly, one of the most exciting breakthroughs in cancer care, their low response rate in most tumor types continues to hinder their clinical application," said Petri Bono, MD, PhD., Chief Medical Officer, Terveystalo Finland and Principal Investigator of the MATINS trial. "There remains an urgent need for effective new treatment options, including novel assets that work synergistically with existing checkpoint inhibitors to ignite and amplify the patient’s immune response."
These data build on Faron’s continued research to identify the patient population most likely to benefit from bexmarilimab treatment and follow the Company’s earlier findings, announced in December 2021, that patients with low baseline serum levels of serum interferon gamma (IFNy) and tumor necrosis factor alpha (TNFa) were more likely to experience clinical benefit following treatment with bexmarilimab. Those patients with immunologically cold tumors also exhibited an ignition of immune response, as indicated by increased levels of IFNy following therapy, which suggests bexmarilimab may serve as a catalyst for the immune system allowing initially checkpoint inhibitor resistant or ineligible patients to become responsive to PD-1 blockade.
"Using a validated staining technique, these preliminary biomarker analyses indicate that bexmarilimab treatment may benefit patients whose tumors express low levels of PD-L1 and higher levels of CLEVER-1 positive intra-tumoral cells, which is opposite to what is usually seen with checkpoint inhibitors and other T cell activating agents," said Marie-Louise Fjällskog, M.D., Ph.D., Chief Medical Officer of Faron. "We are encouraged by this data as it furthers our belief that bexmarilimab has the potential to bring the promise of immunotherapy to a much broader patient population both as a monotherapy and in combination with currently approved anti-PD-1/L1 therapies."
About Bexmarilimab
Bexmarilimab is Faron’s wholly-owned, investigative precision immunotherapy with the potential to provide permanent immune stimulation for difficult-to-treat cancers through targeting myeloid cell function. A novel anti-Clever-1 humanised antibody, bexmarilimab targets Clever-1 positive (Common Lymphatic Endothelial and Vascular Endothelial Receptor 1) tumour associated macrophages (TAMs) in the tumour microenvironment, converting these highly immunosuppressive M2 macrophages to immune stimulating M1 macrophages. In mouse models, bexmarilimab has successfully blocked or silenced Clever-1, activating antigen presentation and promoting interferon gamma secretion by leukocytes. Additional pre-clinical studies have proven that Clever-1, encoded by the Stabilin-1 or STAB-1 gene, is a major source of T cell exhaustion and involved in cancer growth and spread. Observations from clinical studies to date indicate that Clever-1 has the capacity to control T cell activation directly, suggesting that the inactivation of Clever-1 as an immune suppressive molecule could be more broadly applicable and more important than previously thought. As an immuno-oncology therapy, bexmarilimab has potential as a single-agent therapy or in combination with other standard treatments including immune checkpoint molecules in both solid tumors and hematologic malignancies. Beyond immuno-oncology, it offers potential in infectious diseases, vaccine development and more.
About MATINS
The MATINS (Macrophage Antibody To INhibit immune Suppression) study is a first-in-human open label phase I/II clinical trial investigating the tolerability, safety and efficacy of bexmarilimab in ten different hard-to-treat metastatic or inoperable solid tumour cohorts – cholangiocarcinoma, colorectal cancer, cutaneous melanoma, ER+ breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, uveal melanoma, pancreatic cancer and anaplastic thyroid carcinoma – which are all known to host a significant number of Clever-1 positive tumour-associated macrophages (TAMs). The completed Part I of the trial dealt with tolerability, safety and dose escalation. The ongoing Part II is focused on identifying patients who show an increased number of Clever-1 positive TAMs and exploring safety and efficacy. Part III will be focused on assessing efficacy. Data from MATINS have shown that bexmarilimab has the potential to be the first macrophage immune checkpoint therapy. To date, the investigational therapy has been shown to be safe and well-tolerated, making it a low-risk candidate for combination with existing cancer therapies, and has demonstrated early signs of clinical benefit in patients who have exhausted all other treatment options.