TolerogenixX Completes Last Patient Transplant in Phase IIb TOL-2 Trial of MIC-Lx, a First-in-Class Immune Tolerance Cell Therapy for Kidney Transplantation
核心洞察
TolerogenixX (搜索) announced the completion of all 63 donor-recipient pair transplants in its randomized, controlled Phase IIb TOL-2 trial evaluating MIC-Lx in living-donor kidney transplantation.
MIC-Lx is a personalized cell therapy designed to induce donor-specific immune tolerance, potentially reducing the need for lifelong systemic immunosuppression and its associated toxicities.
Patients were randomized 2:1 to receive MIC-Lx plus individualized immunosuppression (n=42) or standard-of-care immunosuppression alone (n=21), with the primary endpoint assessing an operational tolerance-like phenotype at day 367.
TolerogenixX (搜索), a clinical-stage biopharmaceutical company headquartered in Heidelberg, Germany, announced on June 29, 2026 that the last patient has undergone kidney transplantation in TOL-2, the company's randomized, controlled Phase IIb clinical trial evaluating MIC-Lx in living-donor kidney transplantation. The milestone marks the completion of the transplantation phase of the study, with all 63 donor-recipient pairs enrolled and treated according to protocol across multiple clinical centers.
The TOL-2 trial (ClinicalTrials.gov identifier: NCT05365672; EudraCT No.: 2021-000561-33) is designed to address one of the most persistent challenges in organ transplantation: the need for lifelong systemic immunosuppression. While kidney transplantation is life-saving, conventional immunosuppressive regimens carry significant long-term burdens, including increased infection risk, drug toxicity, and reduced quality of life. MIC-Lx aims to overcome this limitation by teaching the immune system to accept the donor organ while preserving protective immune function.
Trial Design and Endpoints
In the TOL-2 study, patients were randomized in a 2:1 ratio to receive either MIC-Lx in addition to individualized immunosuppression (MIC group, n=42) or standard-of-care immunosuppression alone (control group, n=21). MIC-Lx is manufactured from donor-derived peripheral blood mononuclear cells obtained by leukapheresis and modified via TolerogenixX (搜索)'s proprietary MIC technology. The personalized cell therapy is administered intravenously to transplant recipients prior to transplantation.
The primary endpoint assesses the achievement of an operational tolerance-like phenotype at day 367 following MIC-Lx administration. This composite endpoint measures 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 parameters.
"The completion of the last patient transplant in TOL-2 puts TolerogenixX (搜索) on a clear pathway towards one of the most important clinical readouts in immune tolerance," said Prof. Dr. 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."
Building on TOL-1 Evidence
The TOL-2 study builds on findings from the earlier TOL-1 Phase Ib trial, in which kidney transplant recipients treated with MIC-Lx demonstrated long-term donor-specific immune tolerance signals, preserved graft function, and reduced use of conventional immunosuppressive medication. TOL-2 was specifically designed to test whether these immune tolerance signals can be reproduced within a rigorous randomized, controlled Phase IIb setting.
"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 Prof. Dr. Christian Morath, CSO of TolerogenixX (搜索). "This study addresses one of the key challenges in kidney transplantation, reducing the burden of lifelong immunosuppression without compromising graft protection."
All patients in the TOL-2 study will continue to be followed according to protocol, including a 12-month primary observation period and subsequent long-term follow-up. TolerogenixX (搜索) expects to publish topline efficacy and safety data in the first half of 2027.
Platform Potential Beyond Kidney Transplantation
TolerogenixX (搜索)'s lead program focuses on living-donor kidney transplantation, but the company is developing MIC-Lx as a potential immune tolerance platform with planned expansion into additional transplant settings and selected autoimmune indications, including systemic lupus erythematosus (搜索) and multiple sclerosis (搜索). MIC production is a standardized process designed for smart manufacturing and scalable roll-out; using cells obtained by leukapheresis, MICs can be manufactured within 24 hours through the company's proprietary process.
Founded in 2016, TolerogenixX (搜索) is a privately held biopharmaceutical company developing personalized therapies to induce antigen-specific immune tolerance. Its proprietary MIC technology aims to modulate the immune system in a targeted manner, potentially reducing the need for long-term systemic immunosuppression across transplantation and autoimmune diseases.