• Multi-centric clinical study in patients with stage 5 chronic kidney disease (CKD) receiving a living donor kidney
• Study of MIC-Lx cell treatment, a potentially curative approach to achieve sustained immune tolerance in transplanted and autoimmune patients as shown in previous Phase Ib study

TolerogenixX GmbH, a biopharmaceutical company developing personalized cellular therapies aimed at achieving sustained immune tolerance to combat organ rejection and autoimmune diseases, today announced that the German regulatory authority Paul-Ehrlich-Institut has approved a Phase IIb clinical trial for TolerogenixX’s MIC-Lx cell therapy designed to induce immune tolerance. The trial codenamed TOL-2 is scheduled to start in Q2, 2022. It is designed as an open, randomized-controlled, multi-center Phase IIb study of individualized immunosuppression with intravenously administered, donor modified immune cells (MIC-Lx) and will be conducted in patients undergoing living donor kidney transplantation, comparing treatment to standard-of-care (SoC).

MIC-Lx is a cell therapy prepared from an organ donor’s peripheral blood mononuclear cells (PBMC) obtained by leukapheresis. Cells are modified using TolerogenixX´ proprietary MIC technology and, subsequently, MIC-Lx is intravenously administered to the organ recipient prior to transplantation.

The TOL-2 trial is planned to enroll 63 transplant couples, consisting of a donor and a transplant recipient. The 63 organ recipients will be randomized 2:1 to treatment with MIC-Lx (MIC group, N=42) or immunosuppression according to standard-of-care (control arm, N=21). Follow up will be conducted 367 (±28) days after MIC application, corresponding to 360 days after transplantation of the living kidney. In addition, a long-term follow-up will be performed for 2 years after the 12-month follow-up period.

Endpoints have been chosen to determine efficacy of MIC treatment in terms of achieving an operational tolerance-like phenotype compared to standard-of-care, among them absence of biopsy-proven acute rejection, graft loss, graft dysfunction, or death on visit day 367 as well as absence of de novo donor-specific human leukocyte antigen (HLA) antibodies. Secondary endpoints comprise, among others, the number of patient-relevant infections during the first year after transplantation.

The Company previously completed the TOL-1 Phase Ib study, in which kidney transplant patients successfully achieved immune tolerance and absence of organ rejection, based on three-year follow-up data. These results were very positively received in an editorial alongside the publication in the Journal of Clinical Investigation in 2020. TolerogenixX also has completed multiple preclinical studies demonstrating application of its technology to achieve antigen-specific immune tolerance and disease-modifying effects in a broad range of autoimmune diseases.

“We are very much looking forward to the start of this important multi-center trial,” said Prof. Dr. Matthias Schaier, CEO of TolerogenixX. “We have already demonstrated efficacy in our Phase Ib trial, and our goal is to prove safety and efficacy again in a broader patient group. If we succeed, MIC-Lx could be the first approach transforming organ transplantation into a truly curative treatment. Patients may need less or short-term medication, have fewer side effects and, most importantly, would be able to fully recover and live a normal life. We are also extremely excited about the potential of our approach in autoimmune diseases.”

PD Dr. Anita Schmitt, CTO of TolerogenixX, added: ”MIC-Lx is an Advanced Therapy Medicinal Product (ATMP) that can be easily manufactured and has no side effects when administered to patients.”

“In our previous clinical study, patients did not experience graft rejection or de novo HLA antibodies, while retaining full immune competence against bacteria and viruses,” said Prof. Dr. Christian Morath, CSO of TolerogenixX. “In addition, graft function was excellent, and it was possible to markedly reduce administration of standard immunosuppressive drugs, so that patients experienced fewer side effects as compared to standard of care.”

About MIC treatment

MIC treatment is a personalized cell therapy approach modulating the immune system via a novel mode of action to achieve a specific and sustained immune tolerance. It can not only be applied to transplant recipients, but also to patients with autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis.

MIC production is fast, safe, and effective. MIC can be manufactured within 24 hours, using cells obtained by leukapheresis. Due to a standardized procedure, MIC production can be scaled up easily and made available globally using the proprietary approach developed by TolerogenixX.