Medigene AG: Medigene reports preliminary efficacy and immune monitoring data of Phase I of Phase I/II MDG1011 trial in blood cancers

Planegg/Martinsried (pta026/03.02.2022/12:20 UTC+1)

• TCR-T immunotherapy MDG1011 is safe, well tolerated and shows clinical and biological activity in patients with late-stage blood cancers
• One patient still under monitoring more than 6 months after treatment

Martinsried/Munich, 3 February 2022. Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical-stage immuno-oncology company focusing on the development of T-cell-based cancer therapies, announces promising preliminary efficacy and immune monitoring data 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 patients with advanced-stage blood cancers (ClinicalTrials.gov Identifier: NCT03503968). Data demonstrating safety and tolerability, with no cases of dose-limiting toxicity (DLT) associated with MDG1011, were published in December 2021.

MDG1011 is a TCR-T immunotherapy directed against the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma). Patients with relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM) were included in the open-label, dose-escalation Phase I part of the study that was conducted at nine clinical centers in Germany. Following standard pre-conditioning, patients received MDG1011 as a single intravenous infusion at specified dose levels of 0.5, 1 or 5 million TCR-transduced T cells per kg body weight. The primary study objectives were to evaluate safety, tolerability, and feasibility to manufacture autologous MDG1011 TCR-T cells for heavily pretreated patients. In addition, preliminary signs of clinical efficacy and immune monitoring data were investigated.

Clinical and biological data analysis

MDG1011 contained CD8+ TCR-T cells showing recognition and killing of specific standardized target cells in vitro and was successfully manufactured for 13 patients. The group of patients included ten with AML, two with MM and one with MDS. Four patients succumbed to disease before treatment could be administered, in line with the severity of the underlying condition of study patients. Thus, nine patients received MDG1011 at one of the three specified dose levels.

Patient immune monitoring included detection of PRAME-specific T cells (MDG1011 TCR-T cells) in blood to determine persistence over time and biomarker tracking of PRAME in bone marrow and/or blood (as an indicator for remaining cancer cells) by qPCR.

• One patient with AML treated at the lowest dose experienced complete remission at week 4 after treatment; however, this clinical response was not sustained, and the patient’s disease progressed 8 weeks thereafter. PRAME expression was slightly increased from baseline at week 4 whereas MDG1011 TCR-T cells were below the detection level.
• Two patients with AML, treated at the intermediate and highest dose respectively, experienced transient grade 1 or 2 cytokine release syndrome (CRS) within 3 days of drug administration, providing evidence of biological activity of MDG1011 therapy in vivo. MDG1011 TCR-T cells were still detectable in both patients at week 4.
• One patient with multilineage MDS and myeloproliferative neoplasm (MPN) treated at the highest dose, remained without apparent progression to secondary AML 3 and 6 months after MDG1011 administration and is still monitored. MDG1011 TCR-T cells were found at weeks 4, 8 and 12 and were still present at lower levels at month 6 after treatment. Bone marrow could not be evaluated in this patient. PRAME signals in blood were no longer detected at week 4 but gradually increased thereafter at 2, 3 and 6 months, remaining clearly below the baseline level. In concordance, blast counts both in blood and bone marrow remained well below baseline.
• MDG1011 TCR-T cells were detected in six of eight evaluable patients at one or more time points within four weeks after administration. TCR-T cells were also present in two patients at later time points, albeit at decreased levels.
• The biomarker PRAME was assessed in bone marrow samples from five patients four weeks after MDG1011 administration compared to baseline. PRAME decreases occurred in three AML and one MM patient while a slight increase was noted in another patient with MM. PRAME decreased in blood at week 4 for two patients treated at the highest dose but increased thereafter.

The preliminary clinical observations in two patients and occurrence of CRS in a further two of the nine heavily pretreated cancer patients are both encouraging and consistent with expectations of an adoptive T cell therapy. These observations are corroborated by the immune monitoring data.

Prof. Simone Thomas, from the Department of Internal Medicine III of the University Hospital Regensburg and Leibniz Institute for Immunotherapy, Principal Investigator of the study: "No immune effector cell-associated neurotoxicity syndrome (ICANS) or DLTs were detected, so MDG1011 appears to be safe and well-tolerated at all three doses. The aforementioned clinical observations taken together with the effect on PRAME levels and the persistence of MDG1011 strongly support the hypothesis of biological activity of MDG1011."

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "We are very pleased that all MDG1011 TCR-T drug products manufactured from such heavily pre-treated patients with a substantial disease burden showed strong functional activity in vitro, leading to detectable biological and/or clinical activity in four patients.

The effects of PRAME-specific TCR-T immunotherapy on cancer cells should be further investigated based on this safe and well-tolerated treatment. The use of higher cell numbers as well as the treatment of patients with less advanced disease stages could further increase the clinical benefit in the future. Based on our strategic shift to development of TCR-T immunotherapy for solid cancer, Medigene has announced previously that the Phase II part of this study will only be conducted with or by a partner; based on overall results from the Phase I part of the study.

Our current development programs in solid cancer concentrate on TCR discovery for novel tumor-specific antigens and implementation of innovative tools to enhance efficacy and improve safety of T-cell-based immunotherapies."

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About Medigene

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard) is a publicly listed biotechnology company headquartered in Planegg/Martinsried near Munich, Germany. With its scientific expertise, Medigene is working on the development of innovative immunotherapies to enhance T cell activity against solid cancers in fields of high unmet medical need. Medigene’s pipeline includes preclinical as well as clinical programs in development.

Medigene’s strategy is to develop its own therapies towards clinical proof-of-concept. In addition, the Company offers selected partners the opportunity to discover and develop therapies on the basis of its proprietary technology platforms. In return for such partnerships, Medigene expects to receive upfront and milestone payments as well as research and development funding and royalties on future product sales.

For more information, please visit https://www.medigene.com

About Medigene’s TCR-Ts

T cells are at the center of Medigene’s therapeutic approaches. With the aid of Medigene’s immunotherapies the patient’s own defense mechanisms are activated, and T cells harnessed in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs). The resulting TCR-Ts should thereby be able to detect and efficiently kill cancer cells.

This approach to immunotherapy aims to overcome the patient’s tolerance to cancer cells and tumor-induced immunosuppression by activating the patient’s T cells outside the body, genetically modifying them with tumor-specific TCRs and finally multiplying them. In this way, large numbers of specific T cells are made available to patients to fight the cancer within a short period of time.

About PRAME

PRAME (PReferentially expressed Antigen in MElanoma) is a tumor antigen of the cancer-testis-antigen family which is over-expressed in various solid tumors. Expression in healthy tissue is limited to the testis, which itself is an immuno-privileged tissue that usually cannot be attacked by the body’s own immune cells. This makes PRAME very suitable as a target antigen for TCR-T therapies.

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.

Medigene

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E-mail: investor@medigene.com

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