HT-KIT

HT-KIT is a novel synthetic antisense oligonucleotide therapeutic designed to target the proto-oncogene cKIT by inducing mRNA frameshifting, leading to exclusion of exon 4 in KIT mRNA and resulting in premature stop codons that reduce KIT protein expression. This mechanism inhibits proliferation, survival, and differentiation of bone marrow-derived hematopoietic stem cells and induces apoptosis in neoplastic mast cells. It is being developed primarily for treatment of rare and aggressive KIT-driven cancers such as systemic mastocytosis (including aggressive systemic mastocytosis, mast cell leukemia), gastrointestinal stromal tumors (GIST), acute myeloid leukemia, and other cKIT-driven malignancies. HT-KIT offers a novel gene-silencing approach that may overcome resistance seen with tyrosine kinase inhibitors targeting KIT. The drug has received orphan drug designation from the FDA for treatment of mastocytosis and is advancing toward clinical trials with preclinical data showing tumor growth inhibition without observable systemic toxicity.[1][3][4][5][6][7][8]