Kylo-0603, a Novel Liver-Targeted THR-β Agonist for NASH, Completes First-in-Human Dosing in Phase I Clinical Trial in China

On March 28, 2023, Kylo-0603, a Thyroid Hormone Receptor-β (THR-β) agonist drug independently developed by Shanghai Hygieia Pharmaceuticals Co., Ltd. for the treatment of Nonalcoholic Steatohepatitis (NASH), successfully completed its first-in-human dosing in Phase I clinical trials at the First Affiliated Hospital of Zhejiang University School of Medicine.

The study (CTR20230472) is a Phase I dose-escalation clinical trial involving single and multiple dosing in healthy subjects. Its primary objective is to evaluate the pharmacokinetic (PK) profile, safety, tolerability, and food effect following single and multiple administrations of Kylo-0603 in Chinese healthy subjects, to support the subsequent clinical development of Kylo-0603 for indications such as non-alcoholic steatohepatitis (NASH).

About Kylo-0603

Kylo-0603 possesses both a GalNAc structure and a T3-like thyroid hormone structure, offering active and highly efficient liver tissue targeting as well as high affinity and selectivity for THR-β. This drug leverages liver targeting to deliver thyroid hormone analogs into the liver, thereby eliminating or reducing side effects on extrahepatic organs. Thus, Kylo-0603 exhibits dual targeting characteristics for the liver and THR-β receptor.

Animal experiments show that Kylo-0603 can first effectively reduce the serum of high-fat diet mice.Cholesterol(Chol), low-density lipoprotein (LDL-C), triglycerides (TG), and alanine aminotransferase (ALT), while also improving NASH conditions in liver tissue. It can halt the progression of liver fibrosis and reverse symptoms akin to hypothyroidism in models. Compared with traditional single-target small molecule drugs, Kylo-0603 is a hepatic-targeted selective THR-β agonist with clear advantages, demonstrating excellent pharmacokinetics and drug safety in preclinical studies, and has the potential to become the best-in-class therapeutic drug in this field.

NASH is a metabolic disorder disease caused by multiple factors, and alsoNon-alcoholic fatty liver disease(NAFLD) progresses to end-stage liver diseases such as cirrhosis, liver failure, or hepatocellular carcinoma, making the early detection and treatment of NASH particularly crucial for controlling disease progression.

It is estimated that by 2030, 357 million people worldwide will have their lives affected by NASH. The number of liver disease patients in China is approximately 400 million, among which the number of non-alcoholic fatty liver disease (NAFLD) patients is the highest, reaching up to 173 million to 310 million people. Globally, the prevalence rate of NAFLD in ordinary adults is 15%-30%, of which 15%-25% progress to NASH, and the incidence of cirrhosis in NASH patients is as high as 15%-25% within 10-15 years. The number of NASH patients in the United States is about 15-30 million, while in China there are approximately 50 million NASH patients.