GSK Discontinues Phase II Trial of LAG-3 Monoclonal Antibody GSK2831781 in Ulcerative Colitis

On January 22, Immutep announced that its partner GSK had terminated the Phase II clinical study of the LAG-3 monoclonal antibody GSK2831781 (IMP731) for active ulcerative colitis. GSK made this decision after completing the planned interim analysis and discussing with the Data Review Committee. Further evaluations of efficacy, safety, and biological mechanisms are ongoing to determine the next steps in the clinical development plan for GSK2831781.

LAG-3 (lymphocyte activation gene 3, LAG-3, CD223) is an immune checkpoint receptor protein primarily expressed on activated T cells, NK cells, B cells, plasmacytoid dendritic cells, and conventional dendritic cells. LAG-3 binds to MHC class II molecules, thereby downregulating T cell activity. Additionally, LAG-3 enhances the suppressive activity of regulatory T cells (Tregs). Therapeutic antibodies targeting LAG-3 can block its inhibitory effects on T cells, thereby enhancing the body’s immune response.

In many autoimmune diseases, chronic T-cell activation is one of the major pathogenic factors. GSK2831781 is a cytotoxic antibody that depletes activated T cells and, in theory, can be used to treat chronic autoimmune diseases.

On January 6, 2011, GSK reached an agreement with Immutep to obtain the global exclusive development rights for GSK2831781, with a total transaction value of £64 million ($100 million), including upfront payments and milestone payments. If the product is commercialized in the future, GSK will also be required to pay additional sales royalties.

Although the Phase II program for ulcerative colitis was terminated, the collaboration between GSK and Immutep remains in effect, and GSK retains exclusive global rights to GSK2831781. In addition to ulcerative colitis, GSK is also developing GSK2831781 for the indication of psoriasis, which is currently in Phase I.

Immutep is a pioneer in the development of LAG-3 immunotherapies for the treatment of cancer and autoimmune diseases. In addition to GSK2831781, which has been licensed to GSK, the company has three other core LAG-3 products in its pipeline: eftilagimod alpha, a first-in-class antigen-presenting cell (APC) activator (a LAG-3 fusion protein developed in collaboration with Pfizer, Merck & Co., and Yiteng Jingang); ieramilimab, an oncology asset for which global rights have been granted to Novartis; and IMP761, a LAG-3 agonist intended for the treatment of autoimmune diseases. GSK’s recent termination of the Phase II program of GSK2831781 for ulcerative colitis will not affect the development plans for Immutep’s other three products.