NY-ESO-1/LAGE-1a / MDG1015

MDG1015 is a first-in-class, 3rd generation TCR-T therapy targeting NY-ESO-1/LAGE-1a (New York oesophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) co-expressing our PD1-41BB costimulatory switch protein (CSP) which armors and enhances the T cells in the immunosuppressive tumor microenvironment (TME). Preclinical MDG1015 data presented at 2023 AACR and ESMO conferences, demonstrates enhanced effector cytokine functionality in vitro with increased and sustained tumor cell killing activity. This data highlighting the enhancement of the TCR-T therapy through the CSP shows MDG1015’s potential to lead to improved clinical outcomes in solid tumors. MDG1015 IND filing is planned for 3Q 2024 and  CTA filing is planned for 4Q 2024.
Gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma were selected as initial clinical indications for the lead program MDG1015. Read more here

  1. Coluccio AACR 2023, 2. Crame ESMO 2023,

Gastric Cancer

  • 5th most common cancer worldwide3
  • 74,000 patients HLA & target positive4,5
  • Around 60% of patients are diagnosed
    with incurable disease6
  • Projected USD 11.5B market in 20307

Ovarian Cancer

  • 8th most common cancer in women8
  • 19,000 patients HLA & target positive 4,9
  • Only 36 % of patients respond to first line treatment (ORR)10,11
  • Projected USD 19.9B market in 203012

Myxoid/Round Cell & Synovial Sarcoma

  • Accounts for 10-20% of soft tissue sarcomas
  • Global incidence with 3,995 patients13
  • Only 15-20% of patients respond to first line treatment (ORR)13
  • Projected USD 1.3B market in 203014

3. Guan et al J Hematol Oncol 16, 57 (2023), 4. Globocan 2022 – data version 02.2024, 5. Blouch et al An of Oncol (2021) 32 sup5:S382-S406, 6. Lordick et al An of Oncol vol 33, issue 10, p1005-1020, Oct 2022, 7. Biospace Stomach Cancer Treatment Market Size, Share, Trends, Report 2022 to 2030 Aug 29, 2022, 8. WCRF accessed 2024, 9. HLA frequencies database, 10. St. Laurent et al JCO 2023 Vol 24 number 2, 11. Moore et al JCO 2023 Vol 41 number 17, 12. Straits research  Global ovarian cancer market size, top share, growth and forecast to 2031 (2021), 13. Florou et al ASCO Educational Book Vol 38, Nr 38, 14. Astute Analytica Soft  Tissue Sarcoma Market – Industry Dynamics, Market Size, and opportunity Forecast to 2030

  1. Coluccio AACR 2023, 2. Crame ESMO 2023,

3. Guan et al J Hematol Oncol 16, 57 (2023), 4. Globocan 2022 – data version 02.2024, 5. Blouch et al An of Oncol (2021) 32 sup5:S382-S406, 6. Lordick et al An of Oncol vol 33, issue 10, p1005-1020, Oct 2022, 7. Biospace Stomach Cancer Treatment Market Size, Share, Trends, Report 2022 to 2030 Aug 29, 2022, 8. WCRF accessed 2024, 9. HLA frequencies database, 10. St. Laurent et al JCO 2023 Vol 24 number 2, 11. Moore et al JCO 2023 Vol 41 number 17, 12. Straits research  Global ovarian cancer market size, top share, growth and forecast to 2031 (2021), 13. Florou et al ASCO Educational Book Vol 38, Nr 38, 14. Astute Analytica Soft  Tissue Sarcoma Market – Industry Dynamics, Market Size, and opportunity Forecast to 2030

Our approach

Using Medigene’s proprietary Allo-HLA TCR priming technology and robotic, high-throughput TCR isolation and characterization processes, an optimal affinity TCR targeting NY-ESO-1/LAGE-1a, in the context of HLA‑A*02 , was generated. The NY-ESO-1/LAGE-1a TCR was co-expressed with a PD1-41BB CSP, an armoring & enhancement technology required to improve the efficacy of TCR-T therapies in solid tumors without compromising on safety. This represents an alternative strategy urgently needed to overcome the immunosuppressive solid tumor microenvironment.

Find out more about Medigene’s TCR Generation Process here

 

Medigene’s lead candidate targeting the well-characterized cancer testis antigen NY-ESO-1 (New York esophageal squamous cell carcinoma 1) / LAGE-1a has shown to be highly expressed in a wide variety of cancer types. MDG1015 is a 3rd generation NY-ESO-1 / LAGE1-a targeted TCR-T Therapy – sensitive, specific TCR with a favorable safety profile, combined with our PD1-41BB costimulatory switch protein.

MDG1015 displayed increased T cell functionality as means of secretion of multiple cytokines when compared to the TCR without PD1-41BB switch protein “naked TCR” (TCR) or untransduced cells (UT) (Figure 1).

Figure 1:
TCR-T functionality with MDG1015 vs. naked TCR