On September 18, 2023 Medigene AG (Medigene, the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported 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 (Press release, MediGene, SEP 18, 2023, View Source [SID1234635218]).

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Medigene’s end-to-end (E2E) platform, has successfully generated not one but three KRAS G12V-HLA-A*11 TCRs, each with distinct, multiple HLA-A*11 subtype recognition patterns that exceed the Company’s selection criteria for highly specific, sensitive and potentially safer (3S) TCRs. After deploying Medigene’s proprietary algorithms for evaluation of the unique characteristics of each of the 3S TCRs, including peptide specificity, tumor cell recognition and off-target toxicity, the Company has prioritized one of the 3S TCRs as the lead to move forward to the pre-clinical stage for Medigene’s MDG2011 program.

"The unique approach of our E2E platform to generate and optimize 3S TCRs, has continued to deliver above expectations and we are delighted to have been presented with the positive challenge of having to select a lead from three strong candidates for our MDG2011 program targeting KRAS G12V-A11," said Dr. Selwyn Ho, Chief Executive Officer at Medigene.

"The selection of this first mKRAS (mutant KRAS) lead TCR further validates our capabilities to generate 3S TCRs across both neoantigens and cancer-testis antigens. By combining all our TCRs with our PD1-41BB or CD40L-CD28 costimulatory switch proteins, we remain convinced that our approach will consistently deliver best-in-class TCR-T therapies leading to improved outcomes for patients suffering from difficult-to-treat solid tumors. We look forward to presenting the first pre-clinical data on MDG2011 at upcoming scientific conferences in the last quarter of 2023."

The Company’s E2E platform continues to generate 3S TCRs with unique attributes that add additional dimensions to the potential of Medigene’s TCR-T therapies as well as to confirm the Company’s discovery research efforts. One such attribute is the identification of a TCR candidate demonstrating bi-specific recognition for both the KRAS G12V and G12C mutations. Directed TCR discovery efforts in the future will enable identification of an optimal KRAS G12C-specific TCR lead. The two remaining KRAS G12V-A11 TCRs not selected for the MDG2011 program will be added to Medigene’s KRAS TCR library for potential future programs that align the product vision with the profile of each TCR. Patents have been filed for each of the three TCRs.

MDG2011 is the first program of Medigene’s pipeline expansion into a library of neoantigens (also known as oncogenic driver mutations) that comprise multiple KRAS mutations and HLAs (human leukocyte antigens) including, but not limited to:

KRAS G12V-HLA-A*11 (MDG2011)
KRAS G12V-HLA-A*03 (MDG2012)
KRAS G12D-HLA-A*11 (MDG2021)

These TCRs will be combined with the PD1-41BB and/or the CD40L-CD28 costimulatory switch proteins to enhance penetration, proliferation, persistence and enhanced cytotoxic function of Medigene’s TCR-T cells while mitigating the immunosuppressive effects of the tumor microenvironment.

Neoantigens are tumor-specific antigens, which play a critical role in the growth and maintenance of tumors. These mutations are found in many solid tumors and their prevalence varies depending on the cancer type. Importantly, if present, these mutations are found in each tumor cell. KRAS mutations are widely recognized as the most common oncogene mutations in difficult to treat solid tumors existing in ~30% of solid tumors, such as pancreatic, colorectal, endometrial and non-small-cell lung cancer. Global incidence of solid tumors expressing KRAS mutations is estimated to be in excess of 300,000 patients.