Medigene announces indication selection for the clinical development of its TCR-T therapy program in solid tumors
- Gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma selected as initial clinical indications for lead program MDG1015
- MDG1015 is a first-in-class, third generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced by costimulatory switch protein PD1-41BB
- Clinical development in both orphan and more common cancer indications addresses high unmet medical need in large patient populations
Planegg/Martinsried, February 12, 2024. 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 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. MDG1015 is a first-in-class, third generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a), armored and enhanced by costimulatory switch protein PD1-41BB in the context of HLA-A*02 (HLA, human leukocyte antigen). Preclinical data presented in 2023 at the AACR and ESMO conferences demonstrated the clear potential of MDG1015 to improve clinical outcomes in solid tumors.
“The selection of these cancers as targets for MDG1015 is an important step as we advance towards the first-in-human trial. Following recent positive EU and US preliminary regulatory interactions, we remain on track for an IND/CTA approval in the second half of 2024,” said Dr. Selwyn Ho, Chief Executive Officer at Medigene. “While clinical data for engineered cell therapies still in development has shown benefits in some of the selected indications, we believe there is still significant room for improvement in terms of efficacy and durability of progression-free survival. We are confident that MDG1015 as a first-in-class armored and enhanced TCR-T therapy has the potential to address these challenges and improve the quality of life of patients suffering with cancer."
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.[i],[ii],[iii] Additional MDG1015 preclinical data will be presented at upcoming scientific conferences in 2024. Within the current treatment landscape, high NY‑ESO-1 expression is associated with a worse prognosis[iv] and expression increases with advanced disease stage.iv,[v] When looking only at the initially selected solid cancer indications, it is estimated that over 100,000 patients in the world’s top eight economies could be eligible for treatment with MDG1015 based on yearly incidence, target expression and HLA-A*02 positivity. These cancers are also marked by a clear need for new treatment modalities, with estimated five-year survivals for advanced gastric cancer, ovarian cancer and the two subtypes of soft tissue sarcoma as low as 5%-31%.[vi]
About Gastric Adenocarcinoma
Gastric cancer represents the fifth most common cause of cancer deaths worldwide[vii] and 90% of all gastric cancers are gastric adenocarcinomas (GACs).[viii] Overall, ∼60% of people with GAC are not eligible for curative treatment owing to late presentation or comorbidities.viii The 36% of US patients diagnosed with distant metastases have a mere 6.6% 5‑year relative survival rate.vi
About Ovarian Carcinoma
Ovarian cancer is one of the leading causes of cancer deaths among women, and in 55% of US patients distant metastases are present at the time of diagnosis.vi Despite advances in treatment, the prognosis remains poor with a 5-year relative survival rate of 31% for US epithelial ovarian cancer patients with advanced disease.vi
About Myxoid/Round Cell Liposarcoma
Myxoid/round cell liposarcoma is a type of soft tissue sarcoma originating from the fat cells and typically affects younger patients between 30–50 years of age. This disease has an incidence of up to ~1,350 patients in the US which makes it an orphan indication.vi For patients with advanced disease there is an 8% 5-year disease-specific survival rate.[ix]
About Synovial sarcoma
Synovial sarcoma is a type of soft tissue sarcoma characterized by its development in cells around joints and tendons and most often affects adolescents and young adults. The disease has an incidence in line with myxoid liposarcoma, of up to ~1,300 patients in the US making it an orphan indication.vi In 50% of synovial sarcoma cases the disease metastasizes to other areas of the body, most commonly to the lungs. For patients with advanced stage disease, the median overall survival at or after second line therapy is under a year and the 5-year overall survival is 10%.vi,[x]
