MDG2011 / Medigene - LARVOL DELTA

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 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'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'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 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

Medigene presents new data for MDG2011, the first TCR in a novel KRAS library, demonstrating capability of its proprietary E2E Platform to generate multiple enhanced TCR-T therapies against mKRAS G12V A*11 (GlobeNewswire) - "Medigene AG...presents novel preclinical data of their MDG2011 program lead candidates which are optimal affinity Kirsten rat sarcoma viral oncogene homologue mutation (mKRAS)-specific T cell receptors (TCRs) targeting human leukocyte antigens (HLA) A*11, in combination with a PD1-41BB costimulatory switch protein (CSP) at the Society for Immunotherapy of Cancer (SITC) 2023 November 1-5, 2023, in San Diego, USA....The presented data demonstrate, utilizing a high-throughput approach, the generation of optimal affinity TCRs targeting the mKRAS G12V neoantigen presented by multiple HLA-A*11 subtypes through use of the Company’s unique E2E Platform and shows further in vitro characterization with regards to specificity, sensitivity, and safety (3S), of the multiple TCR candidates in combination with the PD1-41BB-CSP."

Preclinical • Oncology

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

Medigene Reports Financial Results and Corporate Update for Q3 2023 (GlobeNewswire) - "Medigene AG...today reported financial results and provided a corporate update for the third quarter of 2023...Due to the prolonged funding and development pause by Hongsheng Sciences of the partnered program that included Medigene’s NY-ESO-1-targeted TCR, the parties have mutually agreed to terminate the partnership agreement as it relates to the NY-ESO-1 asset in Q3 2023....In September, the Company was granted a patent by the European Patent Office protecting its PD1-41BB costimulatory switch protein technology. The patent complements the PD1-41BB IP-portfolio with similar patents already granted in the United States, China and Japan."

Commercial • Patent • Oncology • Solid Tumor

Medigene to present new pre-clinical data for pipeline TCR-T therapies at the ESMO Congress 2023 (GlobeNewswire) - "Medigene AG...will be presenting at the ESMO Congress 2023 being held on October 20-24, 2023, in Madrid, Spain. The data to be presented shows that optimal affinity T cell receptors (TCRs) when combined with Medigene’s PD1-41BB costimulatory switch protein (CSP), provides strong protection of T cell receptor engineered T cells (TCR-T) against multiple mechanisms of solid tumor microenvironment immunosuppression, including CSP-enhanced poly-cytokine secretion, proliferation and mitigation against exhaustion of the TCR-T in vitro."

Preclinical • Solid Tumor

Medigene AG Announces Lead Selection for MDG2011 Representing the First TCR-T Therapy of its KRAS Library (GlobeNewswire) - "Medigene AG...announces today that it has selected its lead candidate for MDG2011, a T cell receptor engineered T cell (TCR-T) therapy targeting KRAS (Kirsten rat sarcoma viral oncogene homologue) G12V with HLA-A*11 and being developed in combination with the Company’s PD1-41BB costimulatory switch protein (CSP) technology....We look forward to presenting the first pre-clinical data on MDG2011 at upcoming scientific conferences in the last quarter of 2023."

Pipeline update • Preclinical • Oncology • Solid Tumor

Medigene Announces Pipeline Expansion into Neoantigens with Programs Targeting Multiple KRAS Mutations and HLAs (GlobeNewswire) - "Medigene AG...today announces its pipeline expansion into neoantigens (also known as oncogenic driver mutations) with KRAS (Kirsten rat sarcoma viral oncogene homologue) as the first target in its MDG10xx program, a T cell receptor engineered T cell (TCR-T) therapy being developed in combination with the company’s PD1-41BB switch receptor technology. The first KRAS antigens and HLAs (human leukocyte antigens) of the library announced today are targeting: KRAS G12V-A11 (MDG2011); KRAS G12V-A03 (MDG2012); KRAS G12D-A11 (MDG2021)..."

Pipeline update • Oncology • Solid Tumor