Long-Term Tegoprubart Data in Kidney Transplantation, With Andrew Adams

New long-term data from the phase 2 BESTOW extension study showed kidney transplant recipients treated with the investigational anti-CD154 monoclonal antibody tegoprubart maintained higher estimated glomerular filtration rate (eGFR) than those receiving tacrolimus through 18 months, with no biopsy-proven acute rejection events observed after 6 months among tegoprubart-treated patients.

In this Q&A, Andrew Adams, MD, PhD, discusses the clinical significance of the findings, the potential role of CD154 blockade in kidney transplantation, and what the upcoming phase 3 program will need to demonstrate.

Q&A: Long-Term Tegoprubart Data in Kidney Transplantation, With Andrew Adams

HCPLive: How meaningful was the absence of biopsy-proven acute rejection after six months with tegoprubart?

Adams: That's a great question. What we saw—and this is similar to other agents in the co-stimulation blockade class—is that most, if not all, rejection tends to occur early after transplant. While we did see some rejection early on with tegoprubart, when we followed patients out to 18 months, the overall rate of rejection became almost equivalent between tacrolimus and tegoprubart. The difference was really the timing of those events.

What was especially interesting was what happened after those rejection episodes. Patients who experienced rejection on tegoprubart, were treated, and remained on therapy didn't appear to pay the same penalty in terms of kidney function. When we compared patients who experienced rejection on tegoprubart with those who rejected on tacrolimus, the tegoprubart-treated patients maintained substantially better kidney function.

That likely relates to a couple of things, including antibody development and the effects of calcineurin inhibitors on scar formation within the kidney during rejection. Even if rejection occurred, patients receiving a more targeted therapy like tegoprubart appeared to preserve kidney function better over the long term, which is ultimately what we're trying to achieve.

HCPLive: What do these findings suggest about CD154 blockade as an alternative approach to calcineurin inhibitor-based immunosuppression?

Adams: Over nearly 30 years of research, we've learned that the CD40-CD154 pathway is one of the most important pathways involved in transplant rejection. There are several T-cell co-stimulation pathways that matter, but if you had to choose one, this is probably the most important.

The challenge historically wasn't understanding the pathway—it was finding a way to block it safely. Earlier antibodies targeting this pathway had complications of their own. Tegoprubart was engineered to overcome those issues, and what we've now seen across studies is that it appears to be well tolerated while also effectively preventing rejection and maintaining good kidney function after transplant.

Beyond kidney transplantation, this pathway may become increasingly important for other areas of transplantation. In xenotransplantation, where genetically modified pig organs are transplanted into human recipients, CD40-CD154 blockade appears to be one of the critical pathways for achieving long-term graft survival in preclinical models. We've already begun to see that approach used on a case-by-case basis in clinical settings, so I think this pathway has implications well beyond traditional kidney transplantation.

HCPLive: As tegoprubart moves into phase 3 development, what will be most important to demonstrate?

Adams: Over the last 50 or 60 years, transplantation has evolved tremendously. By the 1980s and 1990s we had highly effective immunosuppressive therapies like cyclosporine and tacrolimus, and they've given us outstanding first-year transplant success rates—98% to 99% in kidney transplantation.

The challenge is that those medications also carry significant long-term burdens. Patients experience medication-related side effects, and over time we still see loss of kidney function that can ultimately lead to a return to dialysis or the need for another transplant.

The opportunity with a therapy like tegoprubart is to determine whether we can maintain effective immune control while preserving kidney function over the long term using a different approach. As we move into phase 3, it will be important to confirm what we've seen in the phase 1b and phase 2 studies—that the therapy is safe, well tolerated, and capable of reducing some of the side effects associated with traditional calcineurin inhibitor therapy.

One of the more exciting findings from the extension study was the patient-reported outcomes. It's not just about objective measures like kidney function, hypertension, or new-onset diabetes. It's also about how patients feel. Many patients on tacrolimus describe neurologic side effects, including brain fog, where they simply don't feel like themselves. As patients transition away from those traditional medicines, we're seeing improvements in those symptoms with a therapy that's more specifically targeting the immune response.

HCPLive: Is there anything else you'd like clinicians to know about this program?

Adams: I think it's an exciting time across solid organ transplantation, not just kidney transplantation. If the phase 3 data support what we've seen so far, therapies like tegoprubart could have implications for liver, heart, and lung transplantation, where the burden of immunosuppression can be even greater because rejection is more common.

In liver transplantation, for example, we also see downstream effects on kidney function, diabetes risk, and neurologic side effects from current immunosuppressive therapies. Success in kidney transplantation could help establish the foundation for evaluating this approach in other transplant populations.

Beyond traditional organ transplantation, there are also exciting areas like islet cell transplantation and xenotransplantation. Early work from groups such as the University of Chicago and others is exploring tegoprubart in those settings as well. If future studies continue to support these findings, this type of targeted immunomodulation could expand our options for treating patients with end-stage organ disease.

Editor’s Note: Adams reported serving as an advisory board member for Eledon Pharmaceuticals, Miromatrix, and Sanofi, and receiving research funding from Regeneron and Sanofi.

References

1. Eledon Pharmaceuticals, Inc. Eledon presents long-term extension phase 2 BESTOW results at American Transplant Congress showing sustained higher kidney function and improved patient-reported outcomes with tegoprubart compared with tacrolimus. News release. GlobeNewswire. June 22, 2026. Accessed July 10, 2026. https://www.globenewswire.com/news-release/2026/06/22/3315172/0/en/eledon-presents-long-term-extension-phase-2-bestow-results-at-american-transplant-congress-showing-sustained-higher-kidney-function-and-improved-patient-reported-outcomes-with-tego.html

2. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(suppl 3):S1-S155.