Tegoprubart: calcineurin-inhibitor-free islet-transplant immunosuppression

What is being tested

This trial keeps the proven donor-islet-transplant idea but changes the immune-drug strategy. Tegoprubart (AT-1501) is an anti-CD40L monoclonal antibody used as part of a calcineurin-inhibitor-free regimen after allogeneic islet transplantation.¹ The goal is not to avoid immunosuppression; it is to avoid one standard drug class — the calcineurin inhibitors, led by tacrolimus — whose kidney, neurologic, metabolic and cardiovascular toxicities limit the transplant trade-off.¹

What this is not

Tegoprubart is routinely described, in coverage of this trial and elsewhere in the field, as a step toward immunosuppression-free islet transplantation. It is not, and the trial does not claim to be. Three facts settle it.

The trial's own registered title says so. The official title is a pilot study of an antibody against CD40 ligand "to Achieve a Calcineurin Inhibitor-free Immunosuppression Regimen".¹ Calcineurin-inhibitor-free immunosuppression — the investigators are precise about this even when press coverage is not.

Anti-CD40L is itself chronic systemic immunosuppression. CD40-CD40L blockade is costimulation blockade: a drug given indefinitely to stop the immune system rejecting the graft. Its class history is the history of an immunosuppressant, including the thromboembolic complications that halted first-generation anti-CD154 antibodies and drove the Fc-modified redesign that produced AT-1501.² Swapping tacrolimus for tegoprubart changes which immunosuppressant you take for life. It does not end the taking.

The other drugs are still there. This is the detail most write-ups omit. Tegoprubart does not stand alone: the registry's protocol description states that standard immunosuppressive medicines — anti-thymocyte globulin or basiliximab induction, mycophenolate mofetil/sodium, and etanercept — are used to prevent rejection, and that tegoprubart "will be given in combination with these standard immunosuppressive medicines."¹ Tacrolimus is subtracted from a multi-drug regimen; the regimen remains. The eligibility rules read accordingly: no active TB, HIV or hepatitis; prior EBV infection required; no live vaccines; no history of malignancy; no history of thromboembolism.¹ Those are the precautions you take around people whose immune systems you are suppressing.

So: a better-tolerated regimen, plausibly a meaningfully safer one, and a genuine advance for the people who get it. Not an arrival at the drug-free cure, and not on the path to one — it is a different, more modest goal, worth pursuing on its own terms.

Design

The registry lists a Phase 1/2, open-label, non-randomized, single-group pilot study at the University of Chicago, with 70 estimated participants aged 18-65 and study completion estimated for March 2029.¹ The primary endpoint is insulin independence after first and final transplant at Day 75 and Day 365.¹ The 12 people reported on below are the initial cohort, not the finished trial.

Current signal

Eledon reported in March 2026 that the 12-patient cohort was fully enrolled and that 10 participants more than 4 weeks after transplant had achieved insulin independence, with no signs of graft rejection or de novo donor-specific HLA antibodies.³ On June 8, 2026, the company updated the cohort to 12 of 12 participants insulin-independent, producing endogenous insulin and no longer requiring exogenous insulin to manage T1D.⁴

That June release also filled in the detail that matters for judging the regimen:

• Glucose control. Every participant's most recent HbA1c was below 6.5%, with a cohort mean of about 5.4% — down from a baseline mean of about 8.0%, an improvement of roughly 2.6 percentage points. No severe post-transplant hypoglycemia was reported.⁴
• Durability so far. Islet graft function was stable across the cohort over a median of 8 months of post-transplant follow-up, with the longest participant out to 22 months.⁴
• The immune question. No rejection episodes, and no participant developed de novo donor-specific HLA antibodies.⁴
• The toxicity question — the whole point. No evidence of nephrotoxicity, hypertension or neurotoxicity, the side effects commonly seen with the tacrolimus-based regimens this approach is designed to replace.⁴

The same dataset was presented at the ADA 86th Scientific Sessions in June 2026 by the University of Chicago team.⁵ That is clinically important if it holds, but it is still sponsor-reported interim data from a single-arm, open-label study of 12 people. Final peer-reviewed results and longer follow-up are still needed — a median of 8 months says nothing yet about whether these grafts last for years.

And note the shape of the claim. Twelve people came off insulin; zero people came off immunosuppression. "Insulin-independent" is a statement about the pancreas. "Immunosuppression-free" is a statement about the pharmacy. Conflating them is the single most common error in reporting on this field, and it is not an error the investigators are making.

Why it matters

Tegoprubart does not solve donor-islet scarcity and does not create a drug-free cure — participants remain on chronic systemic immunosuppression, tegoprubart included. What it offers is narrower and still worth having: the early absence of kidney, blood-pressure and neurologic toxicity is exactly the signal this regimen was built to produce, and those toxicities are a large part of why islet transplantation has stayed a last-resort option for people with severe hypoglycemia rather than a mainstream one. Tacrolimus is also directly toxic to islets and raises blood sugar — removing it may help the graft as well as the kidney.

So the honest framing is: this could make the immunosuppression bargain less bad, which widens who can reasonably be offered an islet transplant. It does nothing to remove the bargain. The route to a cure that most people would actually accept runs through not needing these drugs at all — and as of July 2026 the only human evidence for that is a single Sana UP421 participant with gene-edited islets and no immunosuppression whatsoever. This trial is on a different road.

References

1. University of Chicago. Safety, Tolerability, and Efficacy of Immunomodulation With a Monoclonal Antibody Against CD40L in Combination With Transplanted Islet Cells in Adults With Brittle Type 1 Diabetes Mellitus. ClinicalTrials.gov NCT06305286. https://clinicaltrials.gov/study/NCT06305286 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

2. Singh AK, Goerlich CE, Zhang T, et al. CD40-CD40L Blockade: Update on Novel Investigational Therapeutics for Transplantation. Transplantation (2023). The review notes that thromboembolic complications seen with unmodified first-generation anti-CD154 antibodies stopped their further use, prompting the Fc-modified second-generation agents such as AT-1501. https://pmc.ncbi.nlm.nih.gov/articles/PMC10287837/ ↩

3. Eledon Pharmaceuticals. Eledon Announces Updated Data from Investigator-Initiated Islet Transplant Trial of Tegoprubart in Patients with Type 1 Diabetes at UChicago Medicine. https://ir.eledon.com/news-releases/news-release-details/eledon-announces-updated-data-investigator-initiated-islet ↩

4. Eledon Pharmaceuticals. Eledon Announces Updated Data from Investigator-Initiated Islet Transplant Trial of Tegoprubart in Patients with Type 1 Diabetes at UChicago Medicine (June 8, 2026 update). https://ir.eledon.com/news-releases/news-release-details/eledon-announces-updated-data-investigator-initiated-islet-0 ↩ ↩² ↩³ ↩⁴ ↩⁵

5. Breakthrough T1D. ADA 2026 recap: days 3 and 4. https://www.breakthrought1d.org/news-and-updates/ada-2026-recap-days-3-and-4/ ↩