Eledon’s Antibody Aids First Gene-Edited, Pig-To-Human Kidney Transplant

In a major medical milestone, Massachusetts General Hospital announced Thursday the world’s first successful transplant of a genetically-edited pig kidney into a 62-year-old man with end-stage kidney disease. Eledon Pharmaceuticals’ tegoprubart, an investigational anti-CD40L antibody, was used following Saturday’s surgical procedure to suppress the patient’s immune system and prevent his body from rejecting the transplanted organ.

The Irvine, Calif.-based clinical-stage biotech is developing tegoprubart to protect transplanted organs and help reduce the risk of organ rejection. Eledon’s stock rose over 12% on Thursday after the announcement.

Mass General and a biotech company called eGenesis, which provided the pig kidney, have been researching this form of transplantation—called xenotransplantation—for five years and published their findings in Nature in October 2023. In Thursday’s announcement, eGenesis said that without genetic modification, a pig kidney “would be immediately rejected by a human recipient” and credited an immunosuppression regimen that included Eledon’s “novel, investigational monoclonal antibody, tegoprubart, targeting the co-stimulatory CD40L pathway” for the success of the historic transplant.

According to Eledon, tegoprubart has been used investigationally to prevent rejection in both kidney and heart pig-to-human xenotransplantations, as well as in human-to-human kidney transplantation.

“Eledon has now participated in both heart and kidney xenotransplant procedures, further demonstrating tegoprubart’s broad potential in transplant,” CEO David-Alexandre Gros said in a statement,” adding that the company is working towards its “goal of developing tegoprubart as a new and better immunosuppressive option for transplant patients.”

Gros told BioSpace the biotech has been working with eGenesis to provide them with tegoprubart across their xenotransplantation efforts, including transplantation in non-human primates and humans.

Saturday’s xenotransplantation was authorized by the FDA under the Expanded Access pathway. Currently, tegoprubart is being evaluated in two clinical trials for kidney allotransplantation, in which an organ from one individual is transplanted to another of the same species with a different genotype, eGenesis said in its announcement.

Founded in 2004, Eledon has made tegoprubart and its multiple mechanisms of action the cornerstone of the company’s therapeutic approach to help effectively manage immune response. The antibody targets and blocks the CD40L which, according to Eledon Chief Science Officer Steven Perrin, was a receptor discovered back in the 1980s that is essential to controlling the activation of T cells and B cells to slow down disease progression.

When CD40L is expressed on activated T cells, it can “talk” to its receptor, a protein on the surface of an antigen-expressing cell, which generates the immune response, Perrin told BioSpace.  

“The activation of this pathway is critical to eliminating viral infections and other things. But, unfortunately, it can become activated in autoimmunity when this pathway recognizes self, and it will start to destroy self and diseases like lupus or rheumatoid arthritis where the immune system thinks your joints are foreign and starts to destroy them,” Perrin said.

The current standard of care when it comes to preventing a transplanted organ from being rejected is a multitude of drug cocktails and therapies, but the mainstay is a drug called tacrolimus. While tacrolimus is good at avoiding failure, the problem is that it is very toxic from the start of administration, mainly affecting the kidneys and cardiovascular system, according to Perrin.

Gros said that the company is looking to remove the toxicity of tacrolimus and to have a potent enough drug for humans to survive xenotransplantation, as the current treatments are not powerful enough. Perrin added that in Mass General’s announcement on Thursday the hospital noted that the standard of care lasts from one minute to five minutes in xenotransplantation before turning black and being rejected by the body.

Eledon is focused on developing tegoprubart to become the standard of care across all transplantation types, including human and non-human organ sources. Gros added that the company will provide more data on a Phase Ib study in kidney transplantation in June 2024 at the American Transplant Congress. In addition, he said Eledon’s Phase II BESTOW study—which puts tegoprubart head-to-head against tacrolimus—is currently enrolling participants with plans to complete enrollment at the end of 2024. The company is also looking to use its anti-CD40L approach to target amyotrophic lateral sclerosis.

Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

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