TolerogenixX GmbH, a biopharmaceutical company developing personalized cellular therapies aimed at achieving sustained immune tolerance to combat organ rejection and autoimmune diseases, has announced that its phase IIb study in renal transplant patients has received the green light to initiate the B arm of the study.
This arm consists of patients receiving minimal immune suppression drugs, reducing tacrolimus and weaning off enteric-coated mycophenolate sodium and methylprednisolone completely. The study enroled 63 transplant couples consisting of a donor and a transplant recipient, respectively. The protocol has been published in BMJ Open.
The company is also publishing five-year follow-up data from a phase I trial of its MIC-Lx cell therapy. The results, published in Frontiers in Immunology, demonstrated that the use of TolerogenixX’s MIC cell therapy prior to transplantation provides long-lasting donor-specific immunosuppression and a sustained, significant increase in regulatory B lymphocytes.
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 and made available globally using the approach developed by TolerogenixX.
TolerogenixX’s MIC-Lx cell therapy is a curative cell treatment to induce donor-specific immune tolerance in transplant recipients and also bears potential for autoimmune patients. In living donor transplantation such as kidney transplantation, peripheral blood mononuclear cells (PBMCs) of the donor are harvested by leukapheresis. Donor PBMCs are then modified by the company’s MIC technology. The resulting cell therapy product, MIC-Lx, is then administered intravenously to the transplant recipient prior to transplantation.
Positive results
TolerogenixX has already reported positive results from the one- and three-year follow-up of 10 transplant recipients of its TOL-1 phase I trial initiated at Heidelberg University Hospital. All patients who had received MIC infusions prior to kidney transplantation in the TOL-1 clinical trial had a favorable clinical course three years after surgery.
In the current publication, the company reported that these 10 MIC patients continued to have excellent clinical outcomes at five years, with stable renal graft function, no donor-specific human leukocyte antigen (DSA) antibodies or acute rejections, and no severe opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher incidence of donor-specific HLA antibodies and more opportunistic infections.
MIC patients continued to show a lack of anti-donor T lymphocyte reactivity in vitro and a high titer of potent regulatory B-cells crucial for a functional immune system five years after surgery. The company said this holds true for the four patients who had been infused with the highest number of cells seven days before surgery, and who received low immunosuppressive medication during follow-up.
Lasting immune suppression
“We are very pleased about these results,” said Christian Morath, CSO of TolerogenixX.
“Five years after transplantation, tolerance is still present. Patients are immunologically better protected, show no severe concomitant symptoms and were able to significantly reduce immunosuppressive therapy.”
“These are exciting and clinically highly relevant data,” added Matthias Schaier, CEO of TolerogenixX.
“We see that our MIC therapy opens the perspective of a transformative and effective treatment option for kidney transplant recipients. It can reduce the side effects of conventional chemical immunosuppression and provide for lasting immune suppression without making the transplant recipients more susceptible to opportunistic infections. We are now conducting a phase IIb study with a larger series of patients treated with MIC and a reduced immunosuppressive drug regimen. Our preclinical studies also demonstrate great potential in autoimmune disease.”
On the back of these results, TolerogenixX also reported a €7 million ($7.6 million) second closing of its Series A financing round now totaling €11.6 million ($12.6 million).
“We are very pleased that we were able to add €7 million to our Series A financing round,” Schaier said.
“In the current financing environment, this is a further validation of our approach, enabling us to successfully complete our phase II program.”