Eledon Pharmaceuticals (NASDAQ:ELDN) used a presentation at the Leerink Partners Global Healthcare Conference to highlight what CEO David-Alexandre Gros described as a rapid expansion in clinical experience with its lead CD40 ligand antibody, tegoprubart, across multiple transplant settings. Gros said that just over five years ago the company had “one non-human primate’s worth of data” in allograft transplantation, and that it has now treated “over 100 humans post-transplant” with tegoprubart, including kidney and islet cell allotransplantation and both heart and kidney xenotransplantation.
Kidney transplant: BESTOW non-inferiority and a focus on safety
Gros focused heavily on results from the company’s controlled Phase 2 BESTOW study in kidney transplantation, along with data from a single-arm Phase 1b trial. He said the key takeaway from BESTOW was that tegoprubart appeared to protect transplanted kidneys while showing what he characterized as “dramatically improved safety versus the historical standard of care,” tacrolimus.
On kidney function, Gros said Eledon had been seeking superiority on eGFR and showed numerical but not statistical superiority. He attributed the lack of statistical separation to an imbalance in the distribution of the highest-quality deceased donor organs. He explained that kidneys are graded on a 1–100 scale, where lower is better, and said the tegoprubart arm received 37% of deceased donor kidneys from the highest-quality group versus 57% in the tacrolimus arm. In his view, that skew may have contributed to stronger-than-expected eGFR performance in the tacrolimus group.
Safety differences versus tacrolimus highlighted
Gros detailed several safety observations from BESTOW that he described as “night and day” compared with tacrolimus. Examples he cited included:
- Tremor rates of roughly one in four patients on tacrolimus versus about 1% to 2% on tegoprubart.
- Higher rates on tacrolimus of new-onset diabetes post-transplant, bacteremia, sepsis, hypertension, and hypertensive crises.
- About 5% of patients in the tacrolimus arm experiencing heart failure versus none in the tegoprubart arm.
He also framed the safety profile as a multi-stakeholder value proposition: tremor and “brain fog” as prominent patient complaints with tacrolimus; post-transplant diabetes as a key physician concern; and delayed graft function as a hospital and payer issue.
On delayed graft function, Gros said 14% of tegoprubart patients experienced delayed graft function versus 25% on tacrolimus, and he stated that tacrolimus patients who required dialysis received dialysis for 1.5 extra days compared with the tegoprubart arm. He said that, for every 100 deceased-donor patients, the difference implied an additional 115 inpatient dialysis days in the tacrolimus group.
Rejection: “not all acute rejection is created equally”
Gros addressed investor questions about acute rejection, arguing that rejection does not necessarily mean organ loss and that current categorization is based on biopsy pathology and historic tacrolimus-era frameworks. He noted that iBox, which he described as a leading predictive algorithm for long-term graft survival, does not include rejection.
In BESTOW, Gros said tegoprubart had numerically more rejection events—about 5% to 6% more patients than tacrolimus—while still meeting the primary non-inferiority endpoint. He also said that patients who experienced rejection, were treated, and remained on tegoprubart ended up with higher kidney function (higher eGFR) than tegoprubart patients who did not experience rejection, a pattern he said was seen in both the Phase 1b and Phase 2 studies. He argued that even if incremental rejection events required short hospitalizations, the overall inpatient burden remained favorable compared with differences observed in delayed graft function.
Regulatory plans: FDA discussions and Phase 3 expectations
Looking ahead, Gros said Eledon expects to speak with the FDA next quarter about a path to approval and Phase 3 trial design for kidney transplantation, with the goal of launching a Phase 3 study by the end of the year. He said the company anticipates a one-year, non-inferiority primary endpoint using the same “historical triple endpoint,” and indicated the FDA had previously communicated a desire to see a minimum of 300 patients with 12 months of data.
He added that the agency is considering iBox as a secondary endpoint. Gros noted that approximately 80% of iBox is driven by eGFR, and said that because BESTOW did not show statistically significant eGFR superiority, it would be “very hard” to show a delta on iBox based on the current data.
Islet cell and liver: updates and new Orphan Drug Designation
In islet cell transplantation, Gros reiterated previously disclosed results from the first six patients, stating that all six were able to stop insulin use and had no severe hypoglycemic events after transplantation. He said the company has now transplanted about 13 subjects (12 de novo and one switch) and plans to take data from its first 10 subjects to the FDA to discuss a path to approval, with an expectation of providing investors more clarity later this year. He described the approach as using deceased donor islets and said Eledon also aims to position tegoprubart as an immunomodulator for emerging stem cell-derived islet technologies that are not fully immunoevasive.
In liver transplantation, Gros noted that the company announced the FDA granted Orphan Drug Designation and said Eledon expects to start a liver investigator-sponsored trial by the end of the year.
On financials, Gros said Eledon ended last year with “just over $130” in the bank and expects that to fund operations into the second quarter of next year, which he said should support planned activities this year and provide flexibility around financing timing.
About Eledon Pharmaceuticals (NASDAQ:ELDN)
Eledon Pharmaceuticals, Inc (NASDAQ:ELDN) is a clinical-stage biopharmaceutical company focused on the discovery and development of therapies for diseases characterized by smooth muscle dysfunction. The company leverages a proprietary ion-channel modulation platform to identify and optimize small-molecule compounds that can either restore or inhibit smooth muscle activity, with the goal of addressing gastrointestinal, hepatic and cardiovascular disorders.
Eledon’s pipeline comprises several preclinical and early-phase clinical programs targeting high-unmet-need indications.
