TolerogenixX, a clinical-stage biopharma company, has completed the transplantation phase of its randomized, controlled Phase IIb TOL-2 clinical trial after the last patient underwent living-donor kidney transplantation.
The milestone marks a major step forward for the company's lead cell therapy candidate, MIC-Lx, and clears the path for topline efficacy and safety results, expected in the first half of 2027.
Kidney transplant recipients typically require lifelong systemic immunosuppressive drugs to prevent organ rejection, exposing patients to increased infection risk, drug-related toxicity and a significant long-term treatment burden.
MIC-Lx is designed to overcome this challenge by training the immune system to accept a donor organ while maintaining normal protective immune function.
The TOL-2 study enrolled 63 living donor-recipient pairs across multiple clinical centers. Participants were randomized in a 2:1 ratio to receive either MIC-Lx alongside individualized immunosuppression (42 patients) or standard-of-care immunosuppression alone (21 patients).
The trial's primary endpoint evaluates the achievement of an operational tolerance-like phenotype 367 days after MIC-Lx administration.
Success is defined by the absence of biopsy-proven acute rejection, graft loss, graft dysfunction or death, as well as the absence of de novo donor-specific HLA antibodies. Secondary endpoints include patient-relevant infections, graft function and additional immunological measures.
The completion of the last patient transplant in TOL-2 puts TolerogenixX on a clear pathway towards one of the most important clinical readouts in immune tolerance,” said Matthias Schaier, CEO of TolerogenixX.
“With all 63 donor-recipient pairs treated according to protocol, we believe MIC-Lx has the potential to transform transplant immunotherapy. This milestone strengthens our clinical, regulatory and partnering pathway as we prepare for topline Phase IIb data in H1 2027.”
MIC-Lx is manufactured from donor-derived peripheral blood mononuclear cells (PBMCs) collected through leukapheresis and modified using TolerogenixX's proprietary MIC technology. The personalized therapy is administered intravenously before transplantation and is designed to induce donor-specific immune tolerance while preserving protective immune responses.
"TOL-2 was designed to test whether MIC-Lx can reproduce the donor-specific immune tolerance signals observed in TOL-1 within a randomized, controlled Phase IIb setting,” said Christian Morath, CSO of TolerogenixX. “This study addresses one of the key challenges in kidney transplantation, reducing the burden of lifelong immunosuppression without compromising graft protection.”
The Phase IIb trial builds on results from the earlier TOL-1 Phase Ib study, in which kidney transplant recipients treated with MIC-Lx demonstrated long-term donor-specific immune tolerance signals, preserved graft function and reduced reliance on conventional immunosuppressive therapy.
Patients enrolled in TOL-2 will continue to be monitored under the study protocol through a 12-month primary observation period followed by long-term follow-up.
