SKY-1214

SKY-1214 is a first-in-class, oral small molecule drug developed by Skyhawk Therapeutics. It functions as an RNA splicing modulator specifically targeting FANCL and FANCI, which are critical components of the Fanconi anemia DNA damage repair pathway. By modulating the splicing of FANCL and FANCI pre-mRNA, SKY-1214 induces exon skipping and introduces premature termination codons, leading to degradation of these mRNAs. This disrupts the DNA repair mechanisms that multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) cells rely on for genomic stability under replicative stress. Preclinical studies have demonstrated potent anti-cancer activity both in vitro and in vivo—including tumor regression in xenograft models—across high-risk MM and NHL cell lines. The compound has shown synergistic effects when combined with standard therapies such as dexamethasone, vincristine, or selinexor[3][5][7][8].