A Phase 2a Study of Kylo-0603 Capsule in Participants With Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic stress-related liver injury closely associated with insulin resistance, with a global prevalence of approximately 25%. It may progress to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to cirrhosis, end-stage liver disease, and increased cardiovascular risk, representing a major unmet medical need. Thyroid hormone receptor beta (THRβ) is predominantly expressed in the liver; selective agonism regulates hepatic lipid metabolism, reduces fat accumulation, suppresses hepatic inflammation and fibrosis, and may delay MASH progression. Kylo-0603 is a liver-targeted, highly selective THRβ agonist modified with GalNAc to enrich hepatic exposure and reduce peripheral effects. This multicenter, randomized, double-blind, placebo-controlled Phase 2a study will evaluate the efficacy, safety, and pharmacokinetics of once-daily oral Kylo-0603 capsules in approximately 120 participants with MASLD and overweight or obesity. Participants will be randomized 1:1:1:1 to Kylo-0603 8 mg, 12 mg, 16 mg, or placebo for 12 weeks. The primary endpoint is the percentage change from baseline in liver fat content assessed by MRI-PDFF at Week 12.