Drug candidates

Bexmarilimab

Igniting the immune system

Bexmarilimab is a first-in-class anti-Clever-1 antibody and one of the most advanced myeloid cell-targeting immunotherapy candidates in clinical development. Macrophage re-programming is an emerging field of immunotherapy that is gaining scientific and clinical validation. We believe bexmarilimab is the best-in-class molecule in the field of macrophage re-programming.

Clever-1 is an immunosuppressive receptor found on macrophages leading to tumor growth and metastases (i.e., it helps cancer to evade the immune system), and a novel immune checkpoint target for drug development.

Discovered by Faron and wholly owned, this investigational immunotherapy is designed to overcome resistance to existing treatments and optimize clinical outcomes, by targeting myeloid cell function, removing immunosuppression and igniting the immune system against cancer.

In combination with standard-of-care, and in both solid tumors and hematologic malignancies, bexmarilimab may improve the efficacy of current cancer treatments and bring the promise of immunotherapy to a broader population.

Priming the tumor microenvironment

Bexmarilimab primes the tumor microenvironment for optimal antitumor immune responses (i.e., to enhance the clinical benefit of concomitant therapies). Clinical data from the Company’s trials of bexmarilimab show increased immune activation as measured by the proinflammatory cytokines, such as interferons (IFNs), supporting potential combinations with standard of care, such as checkpoint inhibitors, which require an IFN response to work.

A broad development program is underway investigating its potential in both hematological malignancies and solid tumors.

Unique mode of action

By targeting the Clever-1 receptor on macrophages, bexmarilimab alters the tumor microenvironment, reprogramming tumor associated macrophages from an immunosuppressive (M2) state to an immunostimulatory (M1) one, upregulating IFN production and antigen presentation, priming the immune system to recognize and attack tumors making cancer cells susceptible to standard of care.

• In solid tumors, the result is increased antigen presentation, secretion of proinflammatory cytokines such as IFN-gamma (which is critical for both innate and adaptive immunity), and activation of T cells, converting nonresponsive ‘cold’ tumors into responsive ‘hot’ tumors.
• In hematological malignancies Clever-1 is not expressed on only on monocytes and macrophages, it is also expressed on the leukemic cancer cells (blasts) themselves. Blasts are a young form of macrophages in the path of becoming an adult, fully differentiated cells, which develop abnormally and cannot be controlled, allowing cancer to spread. This provides bexmarilimab with a dual mode of action, activating an immune response by targeting the monocytes and, at the same time, targeting the leukemic cancer cells themselves, to reduce their metabolic fitness, limit their viability and increase their sensitization to standard therapies.

Traumakine

Traumakine® is Faron’s investigational intravenous (IV) interferon beta-1a (IFN beta-1a) therapy for the prevention of complications from cytokine release syndrome (CRS), or ischemia and hyperinflammatory conditions.

The body’s own, natural production of IFN beta-1a, a key anti- inflammatory signaling protein produced in response to infection, is one of the major innate immunity defenses against virus invasion and cell integrity. IFN beta-1a has previously demonstrated a compelling argument against viral infection and organ protection. Faron is investigating the potential of Traumakine® treatment to further strengthen this natural defense mechanism.

In addition to a profound antiviral effect, when given intravenously, IFN beta-1a upregulates the cell surface protein Cluster of Differentiation 73 (CD73) on endothelial cells. CD73 is an enzyme that suppresses pro-inflammatory responses and protects organs from ischemia and inflammation. The integrity of vasculature and capillaries, which maintain the supply of oxygen in various organs, is sustained by endothelial cells covering the inner surfaces of blood vessels and forming a barrier between circulation and tissues. The breakdown of this endothelial barrier results in micro thrombosis and leakage of blood content into tissues leading to organ damage. Inducing CD73 enzyme expression on vascular endothelium can protect vital organs against ischemia and inflammation, offering a new approach to the treatment of several life-threatening diseases and conditions.

The Company’s INFORAAA study showed Traumakine®-induced upregulation of CD73 was associated with 100% survival in surgically operated ruptured abdominal aorta aneurysm (RAAA) patients. These patients are at high risk of ischemia-reperfusion injury, with expected mortality between 30-40% due to multi-organ failure.

Data from the preclinical Salvage, Preservation, and Advanced Resuscitation through Endothelial Stabilization (SPARES) study, coordinated in conjunction with investigators from Wake Forest Health, Duquesne University, the 59th Medical Wing of the US Air Force and with funding from the US Department of Defense, further highlights the promise of IV IFN beta-1a therapy as a potential therapeutic for emergency and trauma patients, especially when given early on. In the study, primates treated with Traumakine® at the time of major inflammation due to ischemia showed lower levels of muscle and liver damage markers indicating total body protection. The full restoration of limb function was seen with no evidence of muscle atrophy or degeneration.

A collaboration with the Fred Hutchinson Cancer Research Center in Seattle, Washington, is ongoing to further investigate the use of IV IFN beta-1a for the prevention of organ damage from cytokine release syndrome (CRS) and other CAR-T therapy side effects, such as neurotoxicity (ICANs).