Eledon Pharmaceuticals is building upon a deep historical understanding of the CD40/CD40L pathway, as well as preclinical and Phase 1 data, to conduct clinical and preclinical studies in kidney allograft transplantation, xenotransplantation, IgA Nephropathy (IgAN), and amyotrophic lateral sclerosis (ALS). Tegoprubart has received an orphan drug designation from the U.S. FDA for the treatment of ALS.
Every year more than 24,000 people undergo a kidney transplant in the United States, and over 240,000 Americans are living with a transplanted kidney.
Tegoprubart, seeks to address the challenges associated with current immunosuppressive transplantation regimens, such as those that administer calcineurin inhibitors (CNIs). The ability to prevent acute and chronic transplant rejection without the need for CNIs has the potential to transform the clinical management of preventing graft rejection by mitigating the nephrotoxicity and other side effects associated with CNIs, and potentially increasing the functional life of transplanted organs.
In multiple preclinical species and models, blocking CD40L prevented acute and long-term solid organ transplant rejection. Tegoprubart and historical anti-CD40L antibodies have also been shown to prevent allograft transplant rejection as monotherapies in multiple pre-clinical models.
Xenotransplantation is the transplantation of living organs, tissues, or cells from one species to another. Pigs have been identified as a good species for xenotransplantation due to their similarity to humans in terms of organ structure and physiology, in addition to the abundance of the species.
In the past, two key hurdles have prevented successful xenotransplantation:
A recent non-human primate study demonstrated the advantage of blocking CD40 ligand vs. CD40 receptor in xenotransplantation.
IgA Nephropathy (IgAN) is a disease characterized by gradual, progressive kidney function deterioration. IgAN is the most common primary glomerulonephritis effecting over 100,000 Americans. Average age at time of diagnosis is between 20 to 40 years of age. Leakage of blood proteins into the urine, or proteinuria, is a clinical sign of IgAN, and early responses correlate with long-term outcomes. IgAN can be a debilitating disease that may lead to End-Stage Renal Disease (ESRD), dialysis, renal transplant, and death. The standard of care for ESRD is dialysis or kidney transplant, which represents a significant economic burden as well as a major impact on a patient’s quality of life.
In historical preclinical models of autoimmune kidney disease, blocking CD40L signaling ameliorated proteinuria, reduced autoantibodies, decreased immune cell infiltration into the kidneys, and improved survival.
Amyotrophic Lateral Sclerosis (ALS)
ALS affects approximately 30,000 people in the U.S., with approximately 5,000 new cases diagnosed annually. It is characterized by gradual, progressive muscle weakness, ultimately causing patients to lose the ability to ambulate, to swallow and to breathe unassisted.
Despite three FDA approved treatments for ALS, five-year morbidity and mortality remain disappointingly high, with 50% and 80% of ALS patients dying within 3 and 5 years from diagnosis, respectively, mostly from respiratory failure or cachexia (i.e., weight loss and muscle wasting).
In preclinical models of ALS, blocking CD40 Ligand delays disease onset and extends animal survival.