MDG1011 / Medigene - LARVOL DELTA

First-in-Human Study of MDG1011, a TCR-T Therapy Directed Against HLA-A*02:01-Restricted PRAME Antigen for High-Risk Myeloid and Lymphoid Neoplasms. (PubMed, Cancers (Basel)) - "Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden."

First-in-human • Journal • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Melanoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor • HLA-A • PRAME

First-in-Human Study of MDG1011, a TCR-T Therapy Directed Against HLA-A*02:01-Restricted PRAME Antigen for High-Risk Myeloid and Lymphoid Neoplasms (Multidisciplinary Digital Publishing Institute) - "The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Characterization of a 3S PRAME VLD-Specific T Cell Receptor and Its Use in Investigational Medicinal Products for TCR-T Therapy of Patients with Myeloid Malignancies. (PubMed, Cancers (Basel)) - P1/2 | "Preclinical studies demonstrated that MDG1011 displayed key 3S attributes of high specificity, sensitivity, and safety required for regulatory approval of a first-in-human (FIH) clinical study of patients with myeloid malignancies (CD-TCR-001: ClinicalTrials.gov Identifier: NCT03503968). MDG1011 IMP manufacturing was successful at 92%, even including heavily pretreated elderly patients with very advanced disease. The IMPs applied in nine patients all displayed antigen-specific functionality. Elsewhere, clinical study results for MDG1011 showed no dose-limiting toxicity and signs of biological and/or clinical activity in several patients."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD8 • HLA-A • IFNG • PRAME

Medigene AG presents final Phase I data of TCR-T cell therapy MDG1011 in patients with high-risk blood cancers (GlobeNewswire) - P1/2 | N=9 | NCT03503968 | Sponsor: Medigene AG | "Medigene AG...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...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...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."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Medigene AG to present Phase I clinical data for MDG1011 with poster presentation at EBMT 2023 Annual Meeting (GlobeNewswire) - "Medigene AG...will present a poster at the European Society for Blood and Marrow Transplantation (EBMT) 2023 annual meeting being held on April 23-26, 2023 in Paris. The data to be presented show the full results from the CD-TCR-001 dose escalation study with MDG1011, a T cell receptor engineered T cell (TCR-T) therapy directed against the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma) with HLA-A*02:01, in heavily pre-treated patients suffering from different hematological malignancies."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

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) (EBMT 2023) - P1/2 | " Treatment was conducted with MDG1011 after lymphodepletion with fludarabine (25 mg/m² x 3d) and cyclophosphamide (300 mg/m² x 3d) in patients with HLA-A*02:01- and PRAME-positive r/r disease...Grade 1 cytokine release syndrome (CRS) occurred in 1 patient at DL2, grade 2 CRS in 1 patient at DL3 that was manageable with tocilizumab... In heavily pre-treated patients with advanced myeloid and lymphoid neoplasms, treatment with MDG1011 was generally safe and well tolerated up to 5x106 PRAME-specific TCR-T cells/kg. Clinical observations were corroborated by persistence of MDG1011 cells in PB and reductions in PRAME mRNA levels in PB and/or BM."

P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • HLA-A • PRAME

Medigene Presents First Results for Automated Manufacturing of T Cell Receptor Engineered T Cells (GlobeNewswire) - "Prof. Schendel will discuss how the new automated system is being assessed against Medigene’s existing validated multi-modular system using manufacturing benchmarks from the successful production of MDG1011...for its phase 1 trial...in AML, MDS and MM blood cancers...Initial results from the validation process of the new automated system demonstrate that it delivers high viabilities of manufactured cells using enriched CD8 T cells, improved rates of TCR transduction compared to the multi-modular system, and strong functional activities of the drug products after antigen stimulation."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

TCR Modified T Cells MDG1011 in High Risk Myeloid and Lymphoid Neoplasms (clinicaltrials.gov) - P1/2 | N=9 | Terminated | Sponsor: Medigene AG | N=92 ➔ 9 | Trial completion date: Apr 2024 ➔ Jul 2022 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2020 ➔ Jun 2022; The clinical trial is terminated after the completion of phase I without moving to Phase II.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology • HLA-A • PRAME

BioNTech and Medigene Announce Global Collaboration to Advance T Cell Receptor Immunotherapies Against Cancer (GlobeNewswire) - "BioNTech SE...and Medigene AG...announced that they have entered a multi-target research collaboration to develop T cell receptor (TCR) based immunotherapies against cancer. The initial term of the collaboration is three years....BioNTech will acquire Medigene’s next generation preclinical TCR program, which combines TCR-4 of Medigene’s MDG10XX program targeting PRAME with Medigene’s proprietary PD1-41BB switch receptor technology. BioNTech will also obtain the exclusive option to acquire additional existing TCRs in Medigene’s discovery pipeline and will receive licenses to the company’s PD1-41BB switch receptor and precision pairing library."

Licensing / partnership • Oncology

MEDIGENE REPORTS PRELIMINARY EFFICACY AND IMMUNE MONITORING DATA OF PHASE I OF PHASE I/II MDG1011 TRIAL IN BLOOD CANCERS (MediGene Press Release) - P1/2, N=92; NCT03503968; Sponsor: Medigene AG; "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."

Cytokine release syndrome • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

MEDIGENE ACHIEVES POSITIVE PRELIMINARY RESULTS IN PHASE I OF PHASE I/II TRIAL OF TCR-T THERAPY MDG1011 IN BLOOD CANCERS (MediGene Press Release) - P1/2, N=92; NCT03503968; Sponsor: Medigene AG; "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...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."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

"$MDGEF Medigene PRAME MDG1011 with 1st safety results https://t.co/xGRyDLyIhK" (@dhovekamp42)

Clinical • PRAME

"Other PRAME-directed eTCR projects beyond $IMTX IMA203: I see $GSK, $MDGEF (MDG1011) & $BLCM (BPX-701!). Any others?" (@JacobPlieth)

PRAME

MEDIGENE PROVIDES Q2 UPDATE AND 6M REPORT 2020 (MediGene Press Release) - “In June 2021, the last patient was recruited into the third dose cohort of the Phase I part of the Phase I/II clinical trial of MDG1011 against blood cancers. In line with Medigene's focus shifting towards solid cancers, the Company has decided that, contingent on the results from the Phase I part, the Phase II part of the trial would only be conducted with or by a partner. Topline data of the Phase I portion are expected to be published in the second half of 2021.”

P1 data • Hematological Malignancies • Oncology • Solid Tumor

MEDIGENE PROVIDES Q1 2021 UPDATE (MediGene Press Release) - "The PD1-41BB switch receptor is the most advanced of the TCR-T enhancements currently being developed by Medigene....Medigene's PD1-41BB switch receptor turns the tumors' off-signal sent by PD-L1 into an activation signal for the TCR-T cells. As shown at the American Association for Cancer Research (AACR) and the Association for Cancer Immunotherapy (CIMT) virtual meetings in March and May 2021...Medigene continues to enroll and treat patients in the Phase I/II clinical trial of MDG1011 against blood cancers. Dosing of the first three dose cohorts of the Phase I safety and feasibility part of the trial is expected to be completed by the end of Q2 2021."

Enrollment status • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Medigene AG: Medigene provides results for fiscal year 2020 and outlook (PharmiWeb) - “Patient enrollment for the Phase I portion of the Phase I/II trial of MDG1011 in AML and MDS is expected to be completed to enable topline data to be reported in 2021. Depending on the results of the Phase I portion, the Company would intend to partner the project prior to the start of the Phase II portion of the trial. Medigene plans to continue its successful collaborations with bluebird bio and Roivant/Cytovant and will continue to evaluate new partnering opportunities related to its portfolio of product candidates to maximize the Company's value.”

Enrollment status • Licensing / partnership • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Medigene provides results for fiscal year 2019 and outlook (GlobeNewswire) - “bluebird bio announced its intention to start clinical development of the MAGE-A4 TCR-T candidate in 2020; By the end of 2020, Medigene expects to complete dosing of the first three dose cohorts in the dose-escalation part of the Phase I/II trial of MDG1011 in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM); In 2020, Medigene will continue to work on further developing its T cell enhancers, characterizing new TCR candidates and collecting preclinical data for future clinical TCR-T trials, especially targeting solid tumor indications.”

Enrollment status • New trial • Preclinical

Medigene reports financial & business results for the first six months of 2019 (MediGene Press Release) - "Importantly, we initiated patient treatment in our ongoing study with Medigene's first TCR therapy, MDG1011. We also commenced preparations for the Phase I trial of our second TCR therapy, MDG1021, with Leiden University Medical Center, scheduled to start in 2020...In addition, Medigene continues its successful collaboration with bluebird bio and expects to make further progress on TCR candidate discovery. bluebird bio announced to commence clinical development in solid tumors with the first TCR from this partnership (a TCR targeting MAGE-A4) in 2020."

Clinical • Enrollment open • Licensing / partnership • New P1 trial

"---> $MDG1 MDG1011 trial shift https://t.co/BnyVg9lCeX" (@BiotechRadar)

TCR Modified T Cells MDG1011in High Risk Myeloid and Lymphoid Neoplasms (clinicaltrials.gov) - P1/2; N=92; Recruiting; Sponsor: Medigene AG; Trial completion date: Apr 2023 ➔ Apr 2024; Trial primary completion date: Aug 2019 ➔ Aug 2020

Clinical • Trial completion date • Trial primary completion date

Medigene announces dosing of first patient in phase I/II trial with TCR therapy MDG1011 for various blood cancers (MediGene Press Release) - “Medigene AG…announced today that it has dosed the first patient in its first-in-human clinical trial with its TCR therapy candidate MDG1011. The Phase I/II trial investigates the safety and feasibility of MDG1011 for the treatment of various types of blood cancer, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM)….In the Phase I portion of the trial, approximately 12 patients who are suffering from advanced stage AML, MDS and MM and have previously undergone several cycles of standard therapies will be treated with MDG1011.”

Enrollment open