Medigene AG: Medigene presents final Phase I data of TCR-T cell therapy MDG1011 in patients with high-risk blood cancers

Planegg/Martinsried (pta017/24.04.2023/11:00 UTC+2)

• MDG1011 was generally well tolerated in nine heavily pre-treated patients across three ascending dose levels
• No neurotoxicity or dose-limiting toxicities observed
• Two out of nine patients showed early response on treatment at week 4, of which one patient experienced disease progression by week 12
• MDG1011 TCR-T cells detected in peripheral blood within four weeks of treatment, with detection still possible in one patient at twelve months

Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today reports final Phase I dose escalation results from first-in-human Study of HLA-A*02:01-restricted PRAME-specific T cell receptor engineered T cell (TCR-T) therapy (MDG1011) for high-risk myeloid and lymphoid neoplasms (NCT03503968). The data will be presented as an eposter (P227) at the European Society for Blood and Marrow Transplantation (EBMT) 2023 annual meeting, being held April 23-26, 2023, in Paris.

Abstract title: First-in-Human Study of MDG1011, a TCR-T Cell Therapy directed against HLA-A*02:01-Restricted PRAME, for High-Risk Myeloid and Lymphoid Neoplasms (CD-TCR-001)

The poster will be available on Medigene's website at the start of the conference: https://medigene.com/science/abstracts/

MDG1011 is an autologous TCR-T therapy specific for a peptide fragment of PRAME (PReferentially expressed Antigen in MElanoma), a tumor antigen presented on cancer cells by human leukocyte antigen HLA-A*02:01. In the open-label, first-in-human Phase I study conducted at nine clinical centers throughout Germany, thirteen patients (ten with acute myeloid leukemia (AML), two with multiple myeloma (MM) and one with myelodysplastic syndrome and myeloproliferative neoplasm MDS/MPN)) underwent leukapheresis for TCR-T cell manufacture, with four patients succumbing to disease prior to treatment. Subsequently, nine patients with relapsed or refractory AML, MDS/MPN or MM received MDG1011 by single intravenous infusion after a lymphodepleting regimen. Patients received MDG1011 at one of three escalating dose levels (DL): 0.1 (DL1), 1.0 (DL2) or 5.0 (DL3) million TCR-transduced T cells per kg body weight. Immune monitoring of patients included quantification of PRAME levels in bone marrow (BM) and/or peripheral blood (PB) and pharmacokinetics of MDG1011 in PB.

Clinical and biological data analysis

• Of the 124 adverse events (AEs), 54 were > Grade 3 toxicities: 31 related to lymphodepletion and 21 related to the investigational medicinal product. Severe adverse events were reported for 7 of 9 patients undergoing therapy, with two patients exhibiting cytokine release syndrome (CRS) of mild (Grade 1) to moderate (Grade 2) severity, respectively, that were manageable with concomitant IL-6 therapy. No neurotoxicity or dose-limiting toxicities were reported.
• Four patients died from their disease, with none considered related to MDG1011, and none at DL3
• Two out of 9 patients showed early response on treatment at week 4. Of these, one AML patient treated with DL1 showed complete remission at week four, but disease progression was detected at week twelve. One patient with multilineage MDS/MPN treated with DL3 remained stable and did not show any progression to secondary AML throughout the 12-month study.
• MDG1011 TCR-T cells were present in PB of 6 of 8 patients within the first four weeks, with detection still possible in the MDS/MPN patient at twelve months. Four patients (3 AML, 1 MM) displayed decreased PRAME levels in BM, while one patient (MM) showed slightly elevated expression at week four. The MDS/MPN patient showed PRAME levels below baseline in PB throughout the 12-month observation period.

Application of MDG1011 was generally well tolerated by heavily pre-treated patients who received up to 5 million CD8-positive PRAME-specific TCR-T cells/kg body weight. Clinical observations were corroborated by persistence of MDG1011 cells in PB and reduction of PRAME levels in PB and/or BM.

Prof. Dolores Schendel, Chief Scientific Officer at Medigene: "We are pleased to report the end-of-trial results for the Phase I dose escalation study of MDG1011 which showed the potential for MDG1011 in high-risk myeloid neoplasms. We thank all the investigators and their staff who carried out this clinical trial and are indebted to the patients and their families who participated in this first-in-human study. As we have announced previously, despite these encouraging early data, in line with our strategy to focus on solid tumors, we are currently exploring the opportunity to partner MDG1011 for further clinical development."

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About Medigene

Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com

About Medigene's End-To-End Platform

Medigene's immunotherapies help activate the patient's own defense mechanisms by harnessing T cells in the battle against cancer. Medigene's end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The end-to-end platform includes multiple product enhancement technologies, (e.g. PD1-41BB Switch Receptor, Precision Pairing) and development optimization technologies (e.g. Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform's assets & technologies.

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 and blood cancers. 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 renders 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.

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