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/CTA filing is planned for 2H 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

Targeting NY-ESO-1 / LAGE-1a with TCR-T therapies

NY-ESO-1 and LAGE-1a, homologous genes located in the same chromosomal region, encode cancer-testis antigens (CTA) that are expressed in multiple solid tumor types (Figure 1).
In several solid cancer types, NY-ESO-1 expression has been correlated with increased relapse rate, poor treatment response and overall reduced survival. The global target population of solid tumors expressing NY-ESO1 / LAGE-1a is estimated to be more than 200,000 patients each year1.
NY-ESO-1 / LAGE-1a, are well-described targets for cancer vaccines and adoptive cell therapies since only limited expression is observed in normal adult tissues but frequent expression is seen in diverse tumors such as melanoma and carcinoma of the lung, esophagus, ovarian, stomach, prostate, ovary, and bladder, enabling many patient groups to be treated with NY-ESO-1 / LAGE-1a-specific immunotherapies.

Figure 1:
Global Target Population 1,2

  1. Medigene; Internal Sources; SEER, GCO IARC (WHO), GlobalData. (8MM = Top Eight Major Markets – USA, China (Urban only), EU4, Japan, UK)
  2. Corrected for NY-ESO-1 and LAGE-1a expression and HLA-A*02:01 prevalence in each population (Allele Frequencies Net Database)

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