Extending Transplant Life Through Targeted Innovation New

Organ transplantation is fraught with challenges, from donor shortages to eventual transplanted organ failure. The immunosuppressive drugs that are currently the standard of care following transplantation eliminate white blood cells, which broadly affects the immune system. A more targeted approach that modulates the immune system rather than suppressing it has demonstrated the potential for better efficacy and improved safety for transplant recipients.

In this Innovation Spotlight, Steve Perrin, the president and chief scientific officer of Eledon Pharmaceuticals, discusses the challenges surrounding organ transplantation and introduces a new therapy that has shown promise in kidney transplants, islet cell transplants, and xenotransplants.

How difficult is it to obtain a kidney transplant? What are some of the major challenges that patients must face?

Kidney transplantation is the most commonly performed organ transplant procedure worldwide, yet it remains a difficult journey for patients. The most well-known challenge is a severe shortage of donor organs. Despite thousands of lives being saved each year, many more are lost while waiting. In the United States alone, approximately 5,000 patients die each year on the kidney transplant waitlist, a staggering figure that translates to one death for every five transplants performed.

But even for those fortunate enough to receive a kidney, the journey doesn’t end there. Transplanted kidneys, despite advances in surgical technique and immunosuppression, typically function for only 10 to 15 years. Because most transplant recipients are in their 50s or younger at the time of surgery, many will require a second, or even third, transplant during their lifetime. Each subsequent transplant not only brings increased complexity and risk but also consumes a scarce organ that might have otherwise saved another life.

At Eledon Pharmaceuticals, our mission is to extend the functional lifespan of transplanted organs and help address the organ shortage crisis. We are developing next-generation immunosuppressive therapies aimed at improving long-term graft survival. Our lead investigational therapy, tegoprubart, has shown promising potential to better protect transplanted organs than the current standard of care and to potentially do so with fewer side effects. In parallel, we are also exploring how tegoprubart may permit the use of novel sources of organs or cells such as from xenotransplantation, which is the transplantation of organs from animals to humans. This dual approach that Eledon is pursuing, prolonging the life of human-donated organs and expanding the donor pool, is essential if we hope to meet the growing global needs for transplanted organs.

How would expanding organ waiting lists help or hurt? What else can be done to improve the lives of those needing a transplant?

While expanding transplant waiting lists may appear to increase access to life-saving organs, doing so without a corresponding increase in organ availability could actually make the situation worse. Wait times for a kidney transplant in the US typically take years. According to a recent JAMA Network Open study, increasing the size of the kidney transplant waitlist by 10 percent to 50 percent could lengthen average wait times by four to 20 months.¹ To offset this impact, the system would require an additional 2,800 to 11,000 kidneys, an increase in supply that may be unachievable given today’s constraints.

Efforts to expand organ donation through public awareness campaigns, improved donor registration systems, and better utilization of viable deceased donor organs are crucial but have so far been insufficient on their own. Even if every potential donor were identified and organs recovered with optimal efficiency, the gap between supply and demand would likely still persist.

One promising strategy lies in extending the lifespan of transplanted organs, since most of them eventually fail. This places an additional burden on the limited donor pool. Advances in immunology are allowing us to invent new medicines designed to preserve graft function longer, to improve patient outcomes and, hence, to reduce the need for repeat transplants. At Eledon Pharmaceuticals, our investigational therapy tegoprubart is being developed with precisely these goals in mind.

In parallel, expanding the donor organ pool through xenotransplantation, which is the use of animal organs in human transplantation, offers a potentially transformative solution. While this field is still in early stages, recent scientific advances, including pig to human transplants, have revived serious interest in its feasibility. However, success in xenotransplantation will also likely hinge on novel immunosuppression approaches, like tegoprubart, that seek to overcome complex cross-species immune barriers and ensure long-term viability of the graft.

In sum, addressing the transplant crisis requires a multi-pronged approach: increasing organ donation rates, extending the life of transplanted organs through next-generation immunosuppressive drugs, and exploring alternative organ sources such as xenotransplantation. Only by tackling both supply and durability can we truly transform outcomes for the thousands of patients waiting for a chance at a better and longer life.

What is the CD40 ligand and how might targeting it help those in need of a kidney transplant?

CD40 ligand (CD40L), also known as CD154, is a critical immune system protein that plays a central role in the activation and coordination of immune responses. Specifically, CD40L is involved in signaling pathways that regulate how immune cells, particularly T cells and B cells, communicate and respond to perceived threats. In the context of transplantation, this signaling is a key driver of the immune system’s ability to recognize a transplanted organ as foreign and mount an attack against it.

Because of its pivotal role in immune activation, the CD40–CD40L pathway has emerged as an especially attractive target for therapeutic intervention in transplant medicine. Inhibiting CD40L signaling has been shown in preclinical studies to blunt the activation of immune cells that would otherwise contribute to graft rejection. Moreover, beyond simply directly inhibiting immune activation, CD40L inhibition may also foster the development of regulatory T cells (Tregs), a specialized subset of T cells that help maintain immune tolerance and suppress harmful immune responses. As such, it is this combination of immune pathway impacts that makes CD40L blockade a promising strategy for the long-term preservation of health and function of transplanted organs.

What is the mechanism of action of Eledon’s anti-CD40L therapy?

Our investigational therapy tegoprubart is an anti-CD40L antibody designed to block or inhibit the CD40L signaling pathway. This mechanism of action affects the communication between white blood cells and thus decreases the ability of the immune system to activate the helper T cells, natural killer (NK) cells, B cells, dendritic cells, and other antigen-presenting cells involved in generating the response that attacks transplanted organs, as well as increases the activation of Tregs to suppress immune response.

Standard of care immunosuppression drugs aim to wipe out populations of white blood cells, which suppresses the body’s immune system, whereas tegoprubart represents a powerful and more targeted approach to modulating the immune system that has demonstrated the potential for better efficacy and improved safety for transplant recipients. Tegoprubart is the first antibody with high affinity for CD40L to enter clinical trials for patients who receive solid organ transplants, including kidney transplants, and has yielded promising data thus far. In a Phase 1b trial, results from 13 participants who underwent kidney transplantation showed that tegoprubart was generally safe and well tolerated. There were no cases of hyperglycemia, new onset diabetes, or tremor commonly seen with calcineurin inhibitor (CNI) treatment and no cases of graft loss or death. Results also showed that after 90 days post-transplant, patients treated with tegoprubart had kidney function, measured by mean estimated glomerular filtration rate (eGFR), at levels approximately 40 percent above the historical averages seen with tacrolimus.

Does this therapy hold promise beyond kidney transplantation?

Significant prior research of tegoprubart, and inhibition of CD40L, has shown it may play an important role in immunosuppression in patients undergoing kidney transplantation and other types of allotransplantation, or transplanting from one human to another, as well as xenotransplantation. For example, tegoprubart has also shown promise in the prevention of islet transplant rejection in subjects with type 1 diabetes (T1D) in an investigator-initiated trial at the University of Chicago Medicine’s Transplant Institute. In October 2024, positive initial data reported from this trial for the first three islet transplant recipients treated with tegoprubart as part of an immunosuppression regimen demonstrated potentially the first-in-human cases of insulin independence achieved using an anti-CD40L antibody immunosuppression therapy without the use of tacrolimus, the current standard of care. Among the three trial participants who received islet transplant, at the time of the data readout two were functionally cured of T1D—achieving insulin independence and normal hemoglobin A1C levels, a measure of average blood glucose, post-transplant. The third patient, who had only very recently received an islet transplant at the time of the announcement, reduced insulin use by more than 60 percent and showed good glucose control within three days following the procedure.

Tegoprubart has also been used as a cornerstone immunosuppression component in recent historic xenotransplant procedures, including both of the transplants of a genetically modified pig kidney into a human performed at Massachusetts General Hospital, the latest one in January 2025, and the second-ever transplant of a genetically modified pig heart into a human, performed at the University of Maryland Medical Center in September 2023. In addition, a research team at Children’s Hospital Los Angeles is currently using tegoprubart as part of the immunosuppression regimen in a preclinical study evaluating the potential of cardiac xenotransplantation in infants. Groundbreaking new preclinical data presented in April 2025 showed for the first time that xenotransplants of genetically engineered pig hearts may be a potential solution for babies with fatal heart disease and serve as a bridge solution while they are on the human transplant waitlist. In the ongoing preclinical study, eight out of 14 young, size-matched baboons that were transplanted with a genetically modified pig heart survived for several months, with one surviving for nearly 21 months, the longest a nonhuman primate has ever lived with a pig heart.

It is still early days, and we continue to learn with each xenotransplant, but these latest outcomes reinforce how much progress is being made in xenotransplantation and we are proud to play a critical role in advances in the field. Our goal is for tegoprubart to become the next cornerstone immunosuppression therapy in transplantation regardless of the transplant type—kidney, heart, lung or islet cell—and regardless of the source of the organ, whether a living donor, a deceased donor, or in these latest xenotransplants cases, a genetically modified pig.

Looking beyond transplantation, inhibition of CD40L has also demonstrated improved outcomes in many autoimmune models, such as for amyotrophic lateral sclerosis, and major players within the biopharmaceutical industry have recently reported promising clinical data in lupus, multiple sclerosis, rheumatoid arthritis, and Sjogren’s disease.²

Where is the lead compound in its clinical development and what is on the horizon?

Eledon has three clinical trials ongoing in parallel to evaluate tegoprubart for the prevention of organ rejection in patients receiving a kidney transplant. A Phase 1b open-label, single-arm trial with multiple cohorts to optimize the immunosuppression regimen; the international BESTOW Phase 2 trial, which is the first ever head-to-head superiority study comparing an anti-CD40L therapy (tegoprubart) to a CNI (tacrolimus); and a Phase 2 long-term safety and efficacy extension study. The BESTOW multicenter, two-arm, active comparator study has enrolled more than 120 participants to evaluate the safety, pharmacokinetics, and efficacy of tegoprubart compared to tacrolimus, reaching its target enrollment approximately four months earlier than originally planned. Patients who complete the BESTOW trial have the option to enroll in the long-term extension study of tegoprubart.

In August 2025, Eledon plans to report updated interim clinical data from the ongoing Phase 1b open-label trial and in the fourth quarter of this year plans to report topline results from the Phase 2 BESTOW trial of tegoprubart in kidney transplantation. Also, this year Eledon anticipates sharing updated interim clinical data from the investigator-led clinical trial with University of Chicago Medicine’s Transplant Institute for pancreatic islet transplantation in subjects with T1D.

Preclinical and clinical studies have shown that tegoprubart has the potential for better efficacy without the detrimental side effects associated with the current transplant immunosuppression standard of care, and we remain encouraged by the growing body of evidence showing the significant promise of tegoprubart to increase transplant function and longevity thereby transforming both patient survival and quality of life.

What changes do you foresee in the future of organ transplantation?

For the past three decades, innovation in transplant immunosuppression therapy has been remarkably limited. However, that landscape is beginning to shift. Breakthroughs in immunology, gene editing, and cell therapy are ushering in what many view as a new era in transplant medicine. Among these, advances in targeted immunosuppressive therapies, such as tegoprubart, offer the potential to more precisely modulate the immune response, minimize toxicities, and significantly extend the functional lifespan of transplanted organs.

At the same time, the convergence of synthetic biology, xenotransplantation, and regenerative medicine may dramatically expand the available organ supply. From genetically engineered animal organs to lab-grown tissues, these innovations could one day reduce or even eliminate the waitlist altogether, but they too may require novel immunosuppression.

The future of organ transplantation thus lies in both improving how we immunologically protect transplanted organs as well as in fundamentally redefining how we source organs. It’s an extraordinarily exciting time to work in this field, and at Eledon we are proud to contribute to this transformation. Our work with tegoprubart represents a critical step toward building a world where transplanted organs last longer, are more broadly accessible, and help more people reclaim their lives.