Scientists just transplanted a pig kidney into a human—and Eledon’s drug was the secret weapon

Eledon Pharmaceuticals, Inc. has announced a significant advancement in the field of xenotransplantation with the successful use of tegoprubart, its investigational anti-CD40L antibody, as part of an innovative immunosuppression therapy regimen. This breakthrough was achieved during the second-ever transplant of a kidney from a genetically modified pig to a human, performed on 25 January 2025 at Massachusetts General Hospital (MGH) in collaboration with biotechnology partner eGenesis.

This procedure marks another milestone in the ongoing effort to address the global shortage of donor organs through xenotransplantation. Following the surgery, the patient was discharged from the hospital and, for the first time in over two years, no longer requires dialysis—a testament to the potential of tegoprubart in improving long-term transplant outcomes.

What makes tegoprubart critical in xenotransplantation?

Tegoprubart is designed to target the CD40 ligand (CD40L), a protein that plays a pivotal role in activating the body’s immune response. In traditional organ transplants, one of the greatest risks is the body’s immune system rejecting the foreign organ. To prevent this, patients require immunosuppressive drugs that often come with severe side effects. Tegoprubart, as part of an innovative immunosuppression therapy regimen, offers a potentially safer and more effective alternative.

By blocking CD40L, tegoprubart helps inhibit immune cell communication pathways that trigger organ rejection. This mechanism is considered a novel approach to immunosuppressive therapy, as it aims to suppress the immune response without the extensive side effects associated with conventional treatments like tacrolimus.

According to David-Alexandre C. Gros, M.D., Chief Executive Officer of Eledon Pharmaceuticals, “Blocking the CD40 ligand is a critical component of the immunosuppression regimen for effective translation of organ transplants from nonhuman primates into humans. Our anti-CD40L antibody tegoprubart represents a new frontier in immunosuppression therapy, with the potential to improve patient safety and transplant success rates.”

How did tegoprubart perform in the second pig kidney transplant?

In the recent procedure at Massachusetts General Hospital, tegoprubart was used as a cornerstone of the patient’s immunosuppressive treatment. The transplant involved a kidney from a genetically modified pig, engineered by eGenesis to reduce the risk of rejection and other immune complications.

The patient, who had been on dialysis for over two years, showed remarkable improvement following the surgery. Tegoprubart’s role in preventing organ rejection contributed to the patient’s stable recovery, allowing for hospital discharge without the need for further dialysis—a significant indicator of the drug’s effectiveness.

This success mirrors outcomes from the first xenotransplant at MGH in March 2024, where tegoprubart also played a central role. In both cases, the drug was administered investigationally as part of a regimen designed to prevent immune-mediated rejection of the transplanted pig organs.

What does expert analysis reveal about tegoprubart’s potential?

The transplantation community views tegoprubart’s performance as a promising development in overcoming one of the greatest challenges in organ transplantation—effective and safe immunosuppression.

Dr. Leonardo Riella, Medical Director for Kidney Transplantation at Massachusetts General Hospital, emphasised the significance of this progress: “Immunosuppression presents one of the greatest challenges for transplantation in both human and non-human organs. Advancements in immunosuppressive therapies like tegoprubart are critical for improving transplant outcomes and the quality of life for patients globally.”

Tegoprubart is designed not only to prevent acute rejection but also to reduce the long-term complications associated with chronic immunosuppressive drug use, such as increased infection risk and organ toxicity. Its targeted action on the CD40-CD40L pathway enables precise modulation of the immune system, offering a balance between efficacy and safety that current therapies struggle to achieve.

What other clinical applications does tegoprubart have?

Beyond its role in xenotransplantation, tegoprubart is being evaluated in three global clinical studies focused on preventing organ rejection in traditional kidney allograft transplantation. Additionally, it is part of an investigator-sponsored trial aimed at preventing islet transplant rejection in patients with type 1 diabetes (T1D).

In a recent study conducted by the University of Chicago Medicine Transplant Institute, tegoprubart demonstrated groundbreaking results, potentially enabling the first cases of insulin independence in humans using an anti-CD40L monoclonal antibody therapy. Notably, these results were achieved without the use of tacrolimus, the current standard of care, highlighting tegoprubart’s potential to reshape the landscape of transplant immunosuppression.

Moreover, tegoprubart was a key component in the second-ever genetically modified pig heart transplant performed on a human at the University of Maryland Medical Center in September 2023, further validating its versatility and broad therapeutic potential.

What does the future hold for xenotransplantation and Eledon Pharmaceuticals?

The success of tegoprubart in these pioneering xenotransplant procedures signals a transformative shift in the future of organ transplantation. As the demand for donor organs continues to outpace supply, xenotransplantation—once considered a distant possibility—is rapidly becoming a viable solution.

Eledon Pharmaceuticals aims to continue building on its extensive research into anti-CD40L antibody therapies, with tegoprubart positioned at the forefront of this evolution. The company’s ongoing clinical trials and collaborations with leading research institutions reflect a broader commitment to addressing unmet medical needs in transplantation, autoimmune diseases, and even neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS).

If tegoprubart’s current trajectory continues, it could play a pivotal role in making xenotransplantation a routine, life-saving procedure in the coming years, offering hope to thousands of patients awaiting organ transplants worldwide.