Verismo plans to initiate a phase 1, first-in-human trial of SynKIR-110 in the first quarter of 2023.
The FDA has granted orphan drug designation to Verismo Therapeutics’ SynKIR-110, a killer immunoglobulin-like receptor - chimeric antigen receptor (KIR-CAR) T-cell therapy, for the treatment of mesothelin-expressing mesothelioma.1
"Orphan Drug Designation is another major milestone for Verismo following the acceptance of our SynKIR-110™ IND," Bryan Kim, DMD chief executive officer, Verismo Therapeutics, said in a statement.1 "Mesothelioma is a rare and deadly disease for which few other treatment options currently exist. We look forward to working with the mesothelioma community to advance SynKIR-110 as a potential treatment while we continue to expand clinical investigation of this novel platform in other cancers in the solid tumor space.
SynKIR-110 is developed using Verismo’s next-generation KIR-CAR platform that is designed to improve persistence and efficacy against solid tumors.The therapy is being developed for indications including mesothelin-expressing ovarian cancer, mesothelioma and cholangiocarcinoma, which are areas of high unmet medical need, with 5-year survival rates of 49.7%, 30%, and 10%, respectively.
The multi-chain KIR-CAR construct that makes up the platform is based on natural killer (NK) cell receptors and is designed to reduce T cell exhaustion by utilizing the natural on/off switch that will allow cells to rest when not bound to the tumor. The construct is also designed to improve the performance of cells in the solid tumor microenvironment with enhanced surface stability and DAP12 costimulatory chains to aid additional T-cell stimulating pathways and further improve cell persistence.
The FDA cleared Verismo’s investigational new drug application for SynKIR-110 just a few days prior to this announcement.2 Verismo will initiate the phase 1, first-in-human trial STAR-101 (SynKIR T cell Advanced Research) of SynKIR-110 in the first quarter of 2023 for mesothelin-expressing ovarian cancer, mesothelioma and cholangiocarcinoma. The trial’s first clinical site will be the Hospital of the University of Pennsylvania.
"Pre-clinical data have shown enhanced efficacy in murine models with no additional safety concerns. The FDA's clearance of our SynKIR-110 IND represents a new chapter for Verismo as we initiate the first-ever clinical trial for KIR-CAR T cells. It also validates the years of innovative research and hard work by industry pioneers at Penn and the Verismo team," Kim said upon the IND clearance.2
The KIR-CAR platform has demonstrated ongoing regression of solid tumors refractory to traditional CAR T-cell therapies in preclinical studies. Verismo believes the platform will be able to be combined with other emerging techniques including in vivo gene editing, allogeneic cell therapies, advanced T cell selection, and combination therapies to further improve options and outcomes for patients.
"SynKIR-110 is the first product to use the novel KIR-CAR platform. Our technology incorporates a natural on/off switch that allows KIR-CAR T cells to rest when not exposed to tumor antigens, as well as providing an enhanced cell-surface stability of the KIR-CAR," Laura Johnson, PhD, chief scientific officer, Verismo, added to the statement.2 "These enhancements will allow KIR-CAR T cells to better cope with the harsh tumor microenvironment of solid tumors and, potentially, lead to better outcomes for our patients."