Eledon Pharmaceuticals, Inc.

Eledon is a clinical stage biotechnology company that uses its immunology expertise to develop therapies. The company focuses on targeting the CD40 Ligand ("CD40L") pathway to protect transplanted organs and prevent rejection, and to treat amyotrophic lateral sclerosis ("ALS"). Its primary compound in development is tegoprubart, an IgG1, anti-CD40L antibody. Tegoprubart has a high affinity for CD40L, which is a biological target involved in both adaptive and innate immune cell activation and function. This positions it as a target for non-lymphocyte depleting, immunomodulatory therapeutic intervention. Tegoprubart is designed to potentially improve safety and offer pharmacokinetic, pharmacodynamic, and dosing advantages compared to other anti-CD40 approaches. The CD40L/CD40 pathway plays a significant role in immune regulation. CD40L is mainly found on activated CD4+ T cells, platelets, and endothelial cells, while the CD40 receptor is consistently present on antigen-presenting cells like macrophages and dendritic cells, as well as B cells. By blocking CD40L, rather than the CD40 receptor, tegoprubart inhibits both the CD40 and CD11 costimulatory signaling pathways, which may lead to improved effectiveness compared to anti-CD40 receptor methods. Blocking CD40L also increases the polarization of CD4+ lymphocytes to Tregs, a type of T cell that suppresses immune responses, potentially creating a more tolerogenic environment for autoimmune diseases and preventing allograft rejection after solid organ transplantation. Tegoprubart is designed to avoid the risk of thrombolytic events observed with earlier anti-CD40L antibodies. This is achieved through structural modifications that, in preclinical models, have eliminated binding to Fcγ receptors associated with platelet activation, without changing tegoprubart's binding to CD40L. In non-human primate studies, tegoprubart doses up to 200 mg/kg per week for 26 weeks showed no adverse events related to coagulation, platelet activation, or thromboembolism.