Eledon Pharmaceuticals is building upon a deep historical understanding of the CD40/CD40L pathway, as well as preclinical and Phase 1 data, to initiate up to four Phase 2 clinical studies in renal transplantation, islet cell transplantation, autoimmune nephritis, and amyotrophic lateral sclerosis (ALS). AT-1501 has received an orphan drug designation from the U.S. FDA for the treatment of ALS.

  • AT-1501

  • Preclinical

  • Phase 1

  • Phase 2

  • Phase 3

Renal Transplantation
Islet Cell Transplantation
Autoimmune Nephritis
Amyotrophic Lateral
Sclerosis (ALS)


Autoimmune Indications

Renal Transplantation

Over 20,000 people a year undergo a kidney transplant in the United States and another 90,000 people are waiting an average of 3-5 years for a kidney transplant. Since re-transplants represent 10% to 15% of yearly transplants, decreasing the number of necessary re-transplants would increase organ availability for new patients.

AT-1501 seeks to address challenges associated with current immunosuppressive transplantation regimens, such as those using calcineurin inhibitor (CNI)-based therapies. The ability to prevent acute and chronic transplant rejection without the need for calcineurin inhibitors has the potential to transform the clinical management of preventing graft rejection by mitigating the nephrotoxicity, increased opportunistic infections, and increased malignancies associated with CNIs.

In multiple preclinical species and models, blocking CD40L prevented acute and long-term solid organ transplant rejection. AT-1501 and historical anti-CD40L antibodies have also been shown to prevent allograft transplant rejection as monotherapies in multiple pre-clinical models.

Islet Cell Transplantation

Type 1 diabetes (T1D) affects more than one million people in the U.S. Of these individuals, an estimated 70,000 people have a particularly hard to control T1D called Brittle Diabetes (BT1D), which is in part characterized by extreme swings in blood glucose levels and impaired awareness of hypoglycemia.

Islet Cell Transplantation is a potentially under-utilized therapeutic option in people with BT1D in part because current transplant regimens, particularly those with CNIs, may be toxic to the transplanted pancreatic beta cells themselves, and are associated with renal failure, infections, and malignancies. The ability to utilize Islet Cell Transplantation may provide multiple potential benefits, including physiologic regulation of blood glucose, reduction or elimination of insulin injections, improved awareness of hypoglycemia, and slowing or prevention of diabetes complications.

In nonhuman primate models of islet cell transplant, blocking CD40L resulted in prolonged graft function compared to immunosuppressive cocktails containing tacrolimus, and both improved islet cell survival and reduced renal toxicity. In a preclinical study in nonhuman primates, AT-1501 induced long-term metabolic control in the absence of exogenous insulin.

Autoimmune Nephritis

Lupus Nephritis (LN) is a disease characterized by inflammation of the kidneys that is caused by systemic lupus erythematosus (SLE). Approximately 40% of SLE patients develop LN, and U.S. prevalence is estimated at between 65,000 and 120,000 people. Leakage of blood proteins into the urine, or proteinuria, is a clinical sign of LN, and early responses correlate with long-term outcomes. LN can be a debilitating disease that may lead to End-Stage Renal Disease (ESRD), dialysis, renal transplant, and death.

Focal Segmental Glomerulosclerosis (FSGS) is an autoimmune disease that affects children and adults, peaking at ages 6-8 and 20-30, with an estimated prevalence of more than 40,000 people in the U.S. FSGS is the leading pathology of the approximately 20% of patients with glomerulonephropathy who progress to ESRD. Immunotherapy, including glucocorticoids and/or calcineurin inhibitors, improves outcomes, but 25% to 35% of FSGS patients still progress to ESRD.

Currently, there are no FDA or EMA approved therapies for FSGS or LN.

In historical preclinical models of Autoimmune Nephritis, including LN and FSGS, 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 two 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.