David-Alexandre Gros, MD, on Using Tegoprubart to Support Genetically Modified Xenotransplant
The chief executive officer of Eledon Pharmaceuticals discussed the company’s investigational monoclonal antibody and its use along with EGenesis porcine kidney transplant product.
This is the second part of an interview with David-Alexandre Gros, MD. For the first part, click here.
“This is really a very modern approach, a very targeted approach, to immunomodulation. We're no longer talking about wiping out whole white blood cell populations in order to control the immune system. What we're doing is truly changing how the immune system communicates so that it doesn't mount an attack on the transplanted organ.”
EGenesis’ second in-human transplant of EGEN-2784, a porcine kidney with genetic modifications intended to prevent rejection in human patients, was successfully completed earlier this year, according to an announcement made by the company in February. The use of the transplant product, which is intended as an alternative to a human donor kidney transplant for patients with end stage kidney disease, was supported by an immunosuppression regimen that utilizes Eledon Pharmaceuticals’ tegoprubart, an investigational monoclonal antibody directed at the costimulatory CD40L pathway.
During an interview with David-Alexandre C. Gros, MD, Eledon’s chief executive officer, CGTLive® inquired about the role of tegoprubart in providing effective immunosuppression for EGEN-2784. Gros explained that tegoprubart is an immunosuppressive drug with a distinct mechanism compared to traditional transplant treatments, such as calcineurin inhibitor tacrolimus. While its purpose is still to prevent the immune system from attacking a transplanted organ, it works in a different way. Normally, the immune system identifies foreign cells and attacks them, which is a significant challenge in organ transplantation since the body correctly sees the new organ as foreign. This issue has been known to some extent for centuries, as early transplants failed due to a lack of immunosuppression.
More traditional immunosuppression methods suppress the immune system by eliminating large groups of white blood cells. Tegoprubart, however, takes a more refined approach by altering the communication between immune cells rather than destroying them. It specifically targets how T-cells interact with antigen-presenting cells and B-cells. Normally, when T-cells recognize a foreign antigen, they either become killer T cells, which directly attack, or helper T-cells, which activate B-cells to produce antibodies. Tegoprubart prevents this activation, reducing the immune response without killing T-cells. Instead, it encourages the formation of regulatory T-cells, which serve as the immune system’s "brakes," preventing unnecessary attacks. This targeted strategy represents a modern, more precise method of immunomodulation, avoiding broad suppression of immune function while still protecting transplanted organs.
