OSE Immunotherapeutics SA and Nantes University Hospital presented positive interim data analysis from first use of anti-CD28 FR104/VEL-101 in kidney transplantation at the Annual Meeting of the Francophone Society of Transplantation(SFT, Société Francophone de Transplantation) held in Brest, France (December 5 ? 8, 2023). The oral communication, entitled ?First use of FR104, an anti-CD28 molecule in human kidney transplantation, interim analysis?, reported on the first data from the Phase 1/2 clinical trial FIRsT evaluating FR104/VEL-101(emerging locally from the ITUN/CR2TI*) in patients undergoing renal transplant.

This study is sponsored and conducted by the University Hospital of Nantes as part of a collaboration agreement with OSE Immunotherapeutics. The purpose of the FIRsT Phase 1/2 clinical trial is to investigate the safety, tolerability, and pharmacokinetics of FR104/VEL-101, a novel antagonist pegylated anti-CD28 Fab? antibody fragment, as well as its potential clinical efficacy on acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors (NCT number: NCT04837092).

A longer-term follow-up assessment is performed one year after transplantation. One-year safety and efficacy of FR104/VEL-101 is evaluated in terms of renal function, incidence of rejection and suspected potential related adverse events. Ten patient candidates to a first kidney transplant at low risk of rejection, as planned in the protocol, have been included in the FIRsT study for eight analyzable patients (two patients were screened and enrolled but not transplanted for technical reasons).

Tacrolimus (a calcineurin inhibitor) was withdrawn after 6 months post-transplantation. Seven patients completed 1-year treatment with FR104/VEL-101 and one is ongoing (Month 4). At this interim analysis, no safety alert was detected for FR104/VEL-101.

Adverse events were those conventionally observed in kidney transplantation. Pharmacological monitoring made it possible to optimize exposure to FR104/VEL-101 and to maintain high receptor occupancy during the one-year follow-up. No acute rejection under FR104/VEL-101 was observed, especially after discontinuation of Tacrolimus.

One of the key challenges in organ transplantation remains to replace calcineurin inhibitors with efficient immunosuppressive treatments with minimal side effects, particularly on renal function in order to preserve patients? quality of life, and long-term control of post-transplant immune reaction.