MDG1015 / Medigene - LARVOL DELTA

EPITOME-1015-I: a Study to Investigate the Safety and Tolerability of MDG1015 in Patients with Epithelial Ovarian Cancer, Gastroesophageal Adenocarcinoma, Round Cell Liposarcoma And/or Synovial Sarcoma (clinicaltrials.gov) - P1 | N=55 | Not yet recruiting | Sponsor: Medigene AG

New P1 trial • Epithelial Ovarian Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Liposarcoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Medigene AG Announces Refocus of Corporate Strategy and Organizational Realignment (GlobeNewswire) - "Medigene will focus its R&D on generating new TCRs for TCR-guided therapies, and also in advancing its TCR-guided T cell engager (TCR-TCE) MDG3010 program in collaboration with WuXi Biologics. The Company expects to expand its TCR-TCE pipeline through additional partnerships in the near future; The Company will temporarily delay the start of its IND approved, clinic-ready MDG1015 Phase 1 clinical trial while actively seeking partnerships and additional financing options to advance this program into the clinic. In line with the Company’s previous communication, the CTA submission is planned for Q4 2024 to enhance the opportunity for patient recruitment; Medigene will deprioritize further work on all other autologous cell therapy programs including MDG2021...MDG2011 (targeting KRAS G12V with HLA-A*11) and MDG2012. As such, the Company will pause all pre-clinical development work and will actively seek partnerships to advance those programs through pre-clinical stage to IND."

New trial • Pipeline update • Oncology • Solid Tumor

Medigene Presents Unique Approach for Use of Optimal T Cell Receptors in TCR-Guided Modalities at Cell 2024 (GlobeNewswire) - "Data presented and discussed included: Kirsty Crame, MD, participated in the panel...which covered clinical insights, patient considerations, key immunological factors, and manufacturing challenges associated with each therapeutic approach; Kirsty Crame, MD, held the keynote address...providing a comprehensive overview of MDG1015...is on track for CTA filing in Q4 2024; Prof. Dolores Schendel presented....covering Medigene’s End-to-End Platform offering advanced technologies for developing 3S TCRs that can be utilized across multiple modalities. Precision tools enabling selection of 3S TCRs with high specificity, sensitivity, and safety for accurate tumor targeting were presented. Additionally, armoring and enhancement technologies were showcased which empower TCR-T cells to perform optimally within the challenging microenvironments of solid tumors."

Clinical • New trial • Oncology • Solid Tumor

Medigene AG reports Financial Results and Business Update for Q3 2024 (GlobeNewswire) - "We are excited to have announced a three-year strategic partnership with WuXi Biologics to co-research TCR-guided T Cell Engagers (TCR-TCEs) for solid tumors, extending our pipeline. Our MDG3010 program will be a joint development with WuXi Biologics, aiming to create bispecific therapeutics that target cancer cells with precision while minimizing off-target effects. The target for this bispecific will be revealed later."

Commercial • Solid Tumor

Medigene to Present at Upcoming Scientific Conferences (GlobeNewswire) - "Medigene AG...will present at the 16th Annual Protein & Antibody Engineering Summit (PEGS) to be held from November 5-7, 2024 in Barcelona as well as at the Cell 2024 conference by Oxford Global from November 6-8, 2024 in London. In addition, two posters will be presented at the 39th Society for Immunotherapy of Cancer (SITC) from November 6-10, 2024, in Houston, TX, USA."

Clinical data • Oncology

Medigene to Host Virtual R&D Event on Medigene’s Optimal 3S TCRs for TCR-Guided Precision Immunotherapies (GlobeNewswire) - "Medigene AG...will host an R&D Event on Medigene’s optimal 3S (specific, sensitive, and safe) TCRs for TCR-guided precision immunotherapies on Thursday, October 10, 2024, at 4.30 pm CET / 10:30 am ET. A live Q&A session will follow the formal presentations and discussions...Management will discuss the advantages of the Company’s 3S TCRs across a wide range of modalities, including TCR-engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies (TCR-TCE), and TCR-natural killer cell therapies (TCR-NK)...Additionally, Principal Investigator of the EPITOME1015-I trial, Dr. David B. Zhen, MD, Associate Professor at both the Fred Hutchinson Cancer Center and the University of Washington School of Medicine, will provide a comprehensive overview of the Company’s lead program, MDG1015....Finally, the presentation will cover Medigene’s proprietary End-to-End Platform, where multiple technologies can be deployed in a modular approach to generate multiple TCR-guided modalities..."

Pipeline update • Gastric Cancer • Gastrointestinal Cancer • Liposarcoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma

Medigene Announces U.S. FDA Clearance of IND Application for MDG1015, a First-in-Class, Third Generation T Cell Receptor Engineered T Cell (TCR-T) Therapy for Multiple Solid Tumor Indications (GlobeNewswire) - "Medigene AG...announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for its lead program MDG1015 for the treatment of advanced gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma in the phase 1 clinical trial (EPITOME1015-I) ....To complement the IND approval, a Clinical Trial Application (CTA) submission for MDG1015 to the European Medicines Agency (EMA) is on track for the fourth quarter of 2024....Pending additional financing, the Company plans to initiate the phase 1 clinical trial EPITOME‑1015-I, which consists of a dose escalation followed by an expansion segment, by the end of 2024. Based on this timeline, the Company expects to be able to present early data from the dose escalation phase towards the end of 2025."

European regulatory • IND • New P1 trial • P1 data • Gastric Cancer • Liposarcoma • Ovarian Cancer • Solid Tumor • Synovial Sarcoma

Medigene AG Reports Half-Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Research and development expenses increased by 21% to EUR 6.3 million in the first half of 2024 (6M 2023: EUR 5.2 million). The reason for the increase is the focus on the development of TCR-T therapies (MDG1015, MDG2011 and MDG2021) for the treatment of solid tumors and preparatory activities for clinical trials (MDG1015)....Following positive EU and US preliminary regulatory interactions, the Company remains on track for IND-filing in Q3 and CTA-filing in Q4 2024. Subject to financing, the Company expects to initiate a first in-human trial for MDG1015 by the end of 2024....MDG2012: The lead selection for the Company’s third announced KRAS-targeted program MDG2012, KRAS G12V (HLA-A*03), is expected in 2025."

Commercial • IND • New trial • Pipeline update • Oncology

Medigene Presents Efficient 6-Day TCR-T Therapy Production Process with High Stemness (GlobeNewswire) - "Medigene AG...today provides a detailed overview of its lead candidate MDG1015, a first-in-class 3rd generation T cell receptor engineered T cell (TCR-T) therapy, at the 7th Cell and Gene Therapy In-Depth Focus Summit from June 27-28, 2024, in Beijing, China. MDG1015 advances towards the clinic and targets the cancer-testisantigens (CTA) NY-ESO-1 / LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) and is armored and enhanced by the Company’s PD1-41BB costimulatory switch protein (CSP)...Subject to additional financing, the first patient enrollment is anticipated by the end of 2024. Based on this timeline, the Company aims to unveil early data from the dose escalation phase in the fourth quarter of 2025."

Clinical data • New trial • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Liposarcoma • Oncology • Ovarian Cancer • Solid Tumor • Synovial Sarcoma

Medigene AG Expands Patent Portfolio with the Patent Grant for its NY-ESO-1/LAGE 1a Targeted T Cell Receptor in China (GlobeNewswire) - "Medigene AG...announces today that the Company has been issued a patent by the Chinese Patent Office protecting its T cell receptor (TCR) targeting NY-ESO-1 (New York esophageal squamous cell carcinoma 1) and LAGE 1a (L Antigen Family Member-1a), both being well-recognized and validated cancer-testis antigens, expressed in multiple tumor types....This TCR, together with the PD1-41BB costimulatory switch protein, serves as the main component of our lead TCR-T program MDG1015, for the treatment of gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma, for which we remain on track for a US IND submission in the 3rd quarter of this year..."

IND • Patent • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Liposarcoma • Oncology • Ovarian Cancer • Solid Tumor • Synovial Sarcoma

Medigene to Present at the Cell and Gene Therapy In-Depth Focus Summit 2024 (GlobeNewswire) - "Medigene AG...will present virtually at the 7th Cell and Gene Therapy In-Depth Focus Summit taking place from June 27-28, 2024, in Beijing, China....The presentation will feature the Company's lead program MDG1015, a first-in-class third-generation T cell receptor-engineered T cell (TCR-T) therapy. This therapy targets NY-ESO-1/LAGE-1a (New York oesophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) and is enhanced with the PD1-41BB costimulatory switch protein. The first-in-human trial for MDG1015 is planned for gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma, and is on track for Investigational New Drug (IND) filing in Q3 2024 and Clinical Trial Application (CTA) filing in Q4 2024."

IND • New P1 trial • Gastric Cancer • Ovarian Cancer • Synovial Sarcoma

Medigene AG Extends Cash Runway into July 2025 After Successful Oversubscribed Capital Raise (GlobeNewswire) - "Lead program, MDG1015, on track for IND filing in 3Q 2024 and CTA filing in 4Q 2024; Use of proceeds from recent capital raise further advances plans for first patient enrollment in MDG1015 Phase 1 dose escalation trial by end of 2024, subject to additional financing."

Financing • IND • New P1 trial • Oncology • Solid Tumor

Medigene AG Expands Patent Portfolio with European Patent Grant for its NY-ESO-1 – targeted T Cell Receptor (GlobeNewswire) - "Medigene AG...announces today that the Company has been issued a patent by the European Patent Office protecting its T cell receptor (TCR) targeting NY-ESO-1 (New York esophageal squamous cell carcinoma 1), a well-recognized and validated cancer-testis antigen, which is expressed in multiple tumor types...'We are delighted to announce the protection of our NY-ESO-1-targeted TCR in Europe. This TCR, together with the PD1-41BB costimulatory switch protein (CSP), serves as the main component of our lead program MDG1015.'"

Patent • Oncology • Solid Tumor

Medigene AG reports Financial Results and Business Update for Q1 2024 (GlobeNewswire) - "Medigene AG...reported financial results for the first quarter of 2024...From a partnering perspective, the Company’s ongoing global strategic collaboration with BioNTech continues to make good progress and Medigene is working on a number of undisclosed targets....Subsequent to the quarter, on April 23, 2024, the Company announced the launch of a capital raise with subscription rights as part of the Company’s near and medium-term financing strategy. Medigene intends to use the gross proceeds of up to approximately EUR 5.9 million to fund its operating activities and to progress work for the clinical development of the Company’s lead program, MDG1015."

Financing • Licensing / partnership • Oncology • Solid Tumor

Medigene presents streamlined 6-day, high stemness TCR-T therapy production process (GlobeNewswire) - "Medigene AG...today presents a comprehensive overview of its lead candidate MDG1015, a first-in-class 3rd generation T cell receptor engineered T cell (TCR-T) therapy, at CHI's 8^th Annual Immuno-Oncology Summit Europe from April 23-25, 2024, in London. MDG1015, which is advancing towards the clinic, targets NY-ESO-1 / LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) and is armored and enhanced by the PD1-41BB costimulatory switch protein...The presentation with...is available on Medigene’s website....improving efficacy, safety, and ensuring a sustained response are areas needing improvement. Medigene tackles these challenges with a comprehensive approach, which starts with the development of a potential best-in-class, 3S (sensitive, specific, and safe) TCR. Next, the 3S TCR is enhanced with the Company’s exclusive PD1-41BB costimulatory switch protein (CSP) on the engineered TCR-T cells...."

Clinical • Commercial • Oncology • Solid Tumor

Medigene's MDG1015, a Third-Generation TCR T Therapy Incorporating the PD1-41BB Costimulatory Switch Protein, Advancing to the Clinic (IO-SUMMIT EUROPE 2024) - "For TCR-T therapies to be successful in inducing deep and durable clinical responses in solid tumours, a specific, sensitive and safe (3S) TCR, armored and enhanced to overcome the immunosuppressive tumor microenvironment, utilizing a manufacturing process generating an optimal Drug Product, is required. Here we discuss data from MDG1015 (NY-ESO-1/LAGE-1a) and MDG2011 (KRASG12V mutation), third generation, targeted TCR-T therapies co-expressing a 3S TCR and PD1-41BB costimulatory switch protein."

IO biomarker • Oncology • Solid Tumor • CTAG1B • CTAG2 • KRAS • PD-1

Medigene to Present at Upcoming Scientific Conferences (GlobeNewswire) - "Medigene AG...has been invited to present at the CHI's 8th Annual Immuno-Oncology Summit Europe from April 23-25, 2024, in London, UK, as well as at the 7th International Neoantigen Summit to be held in Amsterdam, Netherlands from April 29 - May 1, 2024....The work to be presented will highlight the Company’s lead candidate MDG1015, a first-in-class, third generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/ LAGE-1a (New York oesophageal squamous cell carcinoma 1 / L Antigen Family Member-1a), armored and enhanced with the PD1-41BB costimulatory switch protein (CSP). A first-in-human trial for MDG1015 is planned for gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma with IND/CTA filing targeted for 2H 2024."

IND • New trial • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Liposarcoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma

Medigene Presents Favorable Safety Profile of TCR-T Cells with Costimulatory Switch Protein at AACR Annual Meeting 2024 (GlobeNewswire) - "Medigene AG...today presents superior recombinant T cell receptor (rTCR) engineered T cell functionality as well as a favorable safety profile when rTCR-T cells are armored and enhanced with the PD1-41BB costimulatory switch protein (CSP) at the American Association for Cancer Research (AACR) Annual Meeting 2024 taking place April 5-10, 2024, in San Diego, USA....It represents a safe and effective approach to improve clinical outcomes in hard-to-treat solid tumor indications such as gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma....The data presented in the poster demonstrated that the CSP-mediated costimulatory signal is TCR-gated, such that costimulation only takes place when a specific peptide-human leukocyte antigen (pHLA) complex is present on a tumor cell and triggers a signal through the rTCR expressed by the TCR-T cells."

Preclinical • Solid Tumor

Medigene AG Reports Full-Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Following recent positive EU and US preliminary regulatory interactions, the Company remains on track for an IND/CTA approval in the second half of 2024. Subject to financing, the Company expects to initiate a first in-human trial for MDG1015 by the end of 2024...MDG2021 is our second candidate within the KRAS library targeting KRAS G12D (HLA-A*11) with lead selection expected in the first half of 2024. The lead selection for the Company’s third announced KRAS-targeted program MDG2012, KRAS G12V (HLA-A*03), is expected in 2025."

IND • New trial • Pipeline update • Solid Tumor

Medigene's MDG1015, a Third-Generation TCR T Therapy Incorporating the PD1-41BB Costimulatory Switch Protein, Advancing to the Clinic (IO-SUMMIT EUROPE 2024) - "For TCR-T therapies to be successful in inducing deep and durable clinical responses in solid tumours, a specific, sensitive and safe (3S) TCR, armored and enhanced to overcome the immunosuppressive tumor microenvironment, utilizing a manufacturing process generating an optimal Drug Product, is required. Here we discuss data from MDG1015 (NY-ESO-1/LAGE-1a) and MDG2011 (KRASG12V mutation), third generation, targeted TCR-T therapies co-expressing a 3S TCR and PD1-41BB costimulatory switch protein."

IO biomarker • Oncology • Solid Tumor • CTAG1B • CTAG2 • KRAS • PD-1

Medigene to Present Favorable Safety Profile of TCR-T Cells upon Addition of Costimulatory Switch Protein with a Poster Presentation at AACR 2024 Annual Meeting (GlobeNewswire) - "Medigene AG...will present a poster at the American Association for Cancer Research Annual Meeting (AACR) 2024 taking place from April 5-10, 2024 in San Diego, USA as well as an oral presentation at the ELRIG-Forum 2024 to be held in Darmstadt, Germany on March 7, 2024....The work to be presented shows that recombinant T cell receptor engineered T cells (rTCR-T cells), when armored and enhanced by the PD1-41BB CSP, exhibit superior TCR-T cell functionality and safety as well as a favorable safety profile, revealing the strong potential for improving treatment of cancer patients suffering from advanced solid tumor malignancies....The Company is planning a first-in-human trial for MDG1015...with IND/CTA filing targeted for 2H 2024."

IND • New trial • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Synovial Sarcoma

Medigene AG Expands Patent Portfolio in Japan for iM-TCR Technology to Directly Control TCR-T Safety and Efficacy, In Vivo (GlobeNewswire) - "Medigene AG...announced that the Company has been issued a patent by the Japan Patent Office protecting its inducible Medigene T cell receptor (iM-TCR), a control mechanism to regulate efficacy and safety of its T cell receptor engineered T cell (TCR-T) therapies...TCR-T therapies have demonstrated that they can effectively kill tumor cells. However, excessive activation of T cells may lead to premature exhaustion or cell death, as well as unwanted overactivity and potential development of inflammatory responses in the body. The iM-TCR technology modifies the TCR to achieve control of TCR surface expression, allowing for fine-tuning of activity against tumor cells and thereby reducing potential inflammatory responses in the body....MDG1015 is expected to receive IND/CTA approval in the second half of 2024."

IND • Patent • Solid Tumor

Medigene Announces Indication Selection for the Clinical Development of its Lead 3rd Generation TCR-T Therapy Program in Solid Tumors (GlobeNewswire) - "Medigene AG...today announced the selection of gastric cancer, ovarian cancer and two types of soft tissue sarcomas, myxoid/round cell liposarcoma and synovial sarcoma, as the initial clinical indications for its lead candidate MDG1015....Following recent positive EU and US preliminary regulatory interactions, we remain on track for an IND/CTA approval in the second half of 2024....The indications were selected predominantly based on target and/or PD-L1 expression, with 34-60%, 35-55% and 75-80% of gastric cancer, ovarian cancer and the two subtypes of soft tissue sarcoma expressing NY-ESO-1/LAGE-1a, respectively. Additional MDG1015 preclinical data will be presented at upcoming scientific conferences in 2024."

European regulatory • IND • New trial • Preclinical • Gastric Cancer • Liposarcoma • Oncology • Ovarian Cancer • Soft Tissue Sarcoma • Solid Tumor

Medigene AG Announces Prioritization of Pipeline and Resource Allocation as well as Extension of Cash Runway (GlobeNewswire) - "Medigene’s lead program MDG1015 remains on track for IND/CTA approval in 2H 2024. In line with the Company’s previous communication, the clinical Phase I trial will commence as soon as possible thereafter and remains subject to financing. In 2024, Medigene will focus on the development of two of its previously announced KRAS-targeted programs. By optimizing the technology and processes for the development of MDG2011 (targeting KRAS G12V with HLA-A*11; lead selected in Q3 2023) and MDG2021 (targeting KRAS G12D-HLA-A*11; lead selection in 1H 2024), the Company expects an accelerated development for future KRAS progams as well as other cancer targets. As such, the lead selection for the Company’s third announced KRAS-targeted program MDG2012 has been moved to 2025 (previously 2H 2024)."

IND • Pipeline update • Solid Tumor

Mitigation of tumor microenvironment-mediated immunosuppression using a PD1-41BB switch protein with optimal affinity tcrs for first-in-class, 3rd generation TCR-T therapies (ESMO 2023) - "Methods Two first-in-class, 3rd generation TCR-T therapies, MDG1015 and MDG2011, were developed using optimal affinity TCRs specific for a cancer-testis antigen, NY-ESO-1/LAGE-1a, and a neoantigen, mutated KRAS G12V, respectively. Conclusions The combination of optimal affinity TCRs combined with the PD1-41BB CSP provides strong protection of TCR-T cells against two variable mechanisms of TME immunosuppression based on the demonstration of CSP-enhanced poly-cytokine secretion, proliferation and mitigation against exhaustion in vitro. This observation warrants application in the clinic for this novel approach to potentially overcome the major challenges in solid tumor TMEs."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • Solid Tumor • CTAG1B • CTAG2 • KRAS • PD-1 • TNFRSF9