3D-189 (Galinpepimut-S, GPS)
Galinpepimut-S (GPS) is an WT1-targeting artificially engineered synthetic heteroclitic immunotherapeutic in development for hematological malignancies and solid tumors characterized by an overexpression of the WT1 (Wilms Tumor Protein) antigen. GPS consists of a mixture of four peptide fragments, aiming at optimal immunogenicity and mitigation of immune tolerance by the vaccinated host. GPS targets 25 carefully selected and validated WT1 antigenic epitopes and is applicable across the majority of HLA types on a global scale. It can stimulate a strong immune response of the auto-immune system to the WT1 antigen. Both as monotherapy and in combination with checkpoint inhibitors, GPS can effectively kill tumor cells in the body and enhance the immune system's immune surveillance of tumor cells. In January, 2020, SELLAS commenced a Phase 3 clinical trial (the REGAL study) of GPS in patients with acute myeloid leukemia (AML) who have reached second complete remission.
We obtained IND approval for 3D189 in China in April 2022 and completed the first patient dosing in the Phase I clinical study in China in October 2022 for WT1-positive AML patients in complete remission after completion of at least first-line standard therapy and patients with multiple myeloma, non-Hodgkin’s lymphoma, or high-risk group myelodysplastic syndromes who have achieved complete remission or whose best treatment response is partial remission.
WT-1 and tumor antigen
Wilms Tumor 1 (WT1) is a well-recognized tumor antigen and ranked as top 1 among cancer antigens by the National Cancer Institute. WT-1 is highly and broadly expressed in malignant diseases of both Hematopoietic malignancies and solid tumor, including acute myeloid leukemia (AML), multiple myeloma (MM), lung cancer, esophageal cancer, gastric cancer, biliary duct cancer, and other tumor types, for which there are huge unmet medical needs in China.
Clinical trials of 3D-189
GPS is optimally positioned either as a maintenance monotherapy in various clinical settings where the residual disease burden after prior debulking is very low, such as complete remission status in AML, or in combination with other therapeutic agents, most notably immune checkpoint inhibitors in order to achieve better efficacy. Based on current results of clinical trials, GPS has shown high rates of induction of immunogenicity and the ability to delay disease relapse with an overall low incidence of adverse events, mainly low grade local inoculation reactions. GPS is currently being evaluated in a Phase 3 clinical trial as monotherapy for AML patients who are in second complete remission, and in Phase 1 and Phase 2 studies in combination with checkpoint inhibitors. GPS was evaluated for four indications, which was granted Fast Track Designation or Orphan Drug Product Designation for AML, MPM, and MM and other indications respectively from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).