Medigene AG: Medigene achieves positive preliminary results in Phase I of Phase I/II trial of TCR-T therapy MDG1011 in blood cancers

Medigene AG: Medigene achieves positive preliminary results in Phase I of Phase I/II trial of TCR-T therapy MDG1011 in blood cancers

Planegg/Martinsried (pta/21.12.2021/15:20)
* MDG1011 was safe and well tolerated
* Successful individual manufacturing of MDG1011 drug product from heavily pre-treated patients with advanced-stage blood cancers
* Clinical outcome data from ongoing patient follow-up and data regarding biologic activity of the drug product expected to become available in Q1 2022

Martinsried/Munich, 21 December 2021. Medigene AG (http://www.medigene.com) (Medigene, FSE: MDG1, Prime Standard), a clinical-stage immuno-oncology company focusing on the development of T cell immunotherapies, today announces first promising results from the Phase I part of the Phase I/II clinical trial of Medigene's T cell receptor-modified T cell (TCR-T) therapy MDG1011 in blood cancers, regarding safety, tolerability and feasibility to manufacture TCR-T drug products from highly pre-treated patients with advanced-stage blood cancers (ClinicalTrials.gov Identifier: NCT03503968 (https://clinicaltrials.gov/ct2/show/NCT03503968)).

Clinical outcome data from ongoing patient follow-up and data regarding biologic activity of the drug product from immune-monitoring analyses are expected to become available in Q1 2022.

MDG1011 is a TCR-T immunotherapy directed against the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma) and was manufactured to be administered in a single intravenous dose to patients suffering from relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM) who had previously undergone extensive pre-treatment with standard or experimental therapies. The multi-center, open-label, dose-escalation Phase I part of the study was conducted at 9 clinical centers in Germany. The primary objective of the 3+3 study design is to evaluate the safety and tolerability of MDG1011 and feasibility of manufacturing MDG1011 using autologous CD8+ T cells from the patients. Data cut-off point for reported results herein is 3 months post treatment.

White blood cells were harvested by leukapheresis and enriched for CD8+ T cells from 13 patients with a median age of 65 years (range of 55-80 years). The defined dose levels of 0.5, 1 or 5 million TCR-transduced T cells per kg body weight could be successfully manufactured for 12 of the 13 patients (92.3%). Four patients succumbed to disease before treatment could be administered, in line with the severity of the underlying condition of study patients. Thus, 9 patients were treated with a single intravenous administration of MDG1011.

All patients experienced adverse events, with a preponderance of treatment emergent adverse events (TEAEs) expected for the underlying malignant condition. Grade 1-2 transient cytokine release syndrome (CRS) considered attributable to MDG1011 was experienced by 2 patients, giving direct evidence for biological activity of the infused T cells. Neither immune effector cell-associated neurotoxicity syndrome (ICANS) nor dose-limiting toxicities were reported.

Prof. Simone Thomas, from the Department of Internal Medicine III of the University Hospital Regensburg and Regensburg Center for Interventional Immunology, Principal Investigator of the study: "New treatment options are urgently needed for usually elderly patients with relapsed or refractory AML or MDS after previous treatments, given the high mortality associated with progressive disease. MDG1011 appeared to be safe and well tolerated applying up to 5 million PRAME-specific TCR-transduced T cells per kg body weight, and the trial as such may open an avenue for further investigation of MDG1011."

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "Our special thanks go to all patients who participated in the study and to the entire study team for their efforts and contribution.

Elderly patients who have undergone multiple lines of pre-treatment and suffer from advanced hematological disease, present special challenges for successful manufacture of TCR-Ts. Therefore, we are pleased with the very high rate of success in the manufacture of the necessary numbers of CD8+ PRAME-specific TCR-positive T cells for each individual patient. Observed recoveries from cryopreserved TCR-T cells enabled simplified logistics to be used for delivery of qualified drug products to distant centers for timely application in patients.

Further data on immunological function of TCR-T cells in conjunction with signs of biological activity in vivo and potential impact on clinical outcomes over time, will be provided when current follow-up studies have been completed."