Kasik迪's Novel Drug CS0159 Receives FDA Breakthrough Therapy Designation, Marking a Key Milestone in Global Expansion

VCBeat has learned that Cascade Pharmaceuticals, Inc. announced,Its self-developed Class 1 new drug, CS0159 oral tablets, has received FDA Breakthrough Therapy Designation.Given the outstanding clinical potential of CS0159 in the field of primary biliary cholangitis (PBC), its internationalization process has reached a significant milestone.

CS0159 is a novel, potent, non-steroidal small-molecule agonist of the farnesoid X receptor (FXR), developed through crystal structure-assisted design by the team of Xu Huaqiang, founder of CASCADE, in collaboration with the team of Li Jia from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.CS0159 possesses unique pharmacokinetic properties that enable pulsatile FXR activation, aligning with the natural rhythm of bile acid fluctuations. Once-daily dosing provides superior efficacy while minimizing adverse reactions.This innovative design sets it apart among numerous FXR agonists, holding promise for delivering a superior therapeutic experience to patients.

The FDA’s Breakthrough Therapy Designation is a fast-track mechanism established for drugs intended to treat serious conditions, where preliminary clinical evidence indicates substantial improvement over existing therapies. Obtaining this designation means that CS0159 will benefit from the FDA’s priority review pathway, reducing the standard review timeline from 10 months to 6 months, while also receiving direct guidance from senior FDA officials and the convenience of rolling submission reviews.

Research data indicate that drugs granted Breakthrough Therapy Designation have an average clinical development time that is 30% shorter than that of conventional drugs. This holds significant importance for patients with primary biliary cholangitis (PBC) who are in urgent need of new treatment options, as it will substantially accelerate the market approval process for this innovative therapy.

Dr. Xu Huaqiang, the company’s founder, stated that the FDA’s Breakthrough Therapy Designation affirms CS0159’s ability to address significant unmet clinical needs and marks a critical step toward its global expansion.To date, CS0159 has completed multiple pivotal clinical studies and has received triple designations: FDA Fast Track designation for metabolic dysfunction-associated steatohepatitis (MASH), Orphan Drug designation for primary sclerosing cholangitis (PSC), and Breakthrough Therapy designation.

This triple designation fully demonstrates the significant therapeutic potential of CS0159 as an FXR agonist. In the field of MASH, CS0159 has completed Phase II clinical trials in the United States, showing encouraging efficacy and safety data. In the rare disease area of PSC, its orphan drug designation provides important regulatory and market advantages for future commercialization. Furthermore, the receipt of Breakthrough Therapy Designation for PBC further validates its significant value in the treatment of cholestatic liver diseases.

Currently, the Phase II clinical trial of oral CS0159 tablets for MASH has been completed in the United States, with study results demonstrating excellent performance in improving markers of hepatic steatosis and fibrosis. In China, the core Phase II study of CS0159 for the indication of primary biliary cholangitis (PBC) has been completed, showing significant efficacy and a favorable safety profile. These findings not only provide strong support for FDA Breakthrough Therapy Designation but also lay a solid foundation for the upcoming Phase III clinical trials.

The Phase III clinical trial for PBC has entered the preparatory stage and is expected to officially launch in the second half of 2025.This study will further validate the efficacy and safety of CS0159 in a larger patient population.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease. Its global prevalence has been rising in recent years. The disease progressively destroys the small intrahepatic bile ducts and, if left untreated, can lead to cirrhosis and even liver failure.Currently, approximately 40–50% of patients with primary biliary cholangitis (PBC) exhibit an inadequate response to the first-line therapy ursodeoxycholic acid (UDCA), creating an urgent need for more effective treatment options. To address the clinical needs of this patient population, no new drugs have yet been approved in China.

The unique mechanism of action of CS0159 not only effectively improves cholestasis but also significantly alleviates hepatocellular injury, while avoiding the drug-induced liver injury associated with traditional FXR agonists, thereby offering patients a safer and more effective therapeutic option.

CASCADE is actively expanding its pipeline in liver diseases and metabolic disorders, including novel THR-β agonists, with the potential to offer new therapeutic approaches for metabolic diseases through monotherapy or combination regimens from multiple perspectives.The Phase II clinical trial for the investigational candidate CS060380 in MASH is imminent; meanwhile, another candidate, CS060304, has enrolled multiple cohorts in its SAD study, underscoring the company’s robust expertise in nuclear receptor drug development.

By combining drugs with these diverse mechanisms of action, CASCADE is poised to deliver more precise and personalized treatment regimens for complex metabolic diseases.

Cascade Pharmaceuticals, Inc. (Shanghai), established in 2017, is an emerging biotechnology company specializing in the source discovery and clinical development of innovative drugs targeting nuclear receptors and G protein-coupled receptors (GPCRs). Recognized as a Shanghai “Specialized, Refined, Differential, and Innovative” enterprise, the company focuses primarily on metabolic diseases such as metabolic dysfunction-associated steatohepatitis (MASH) and primary biliary cholangitis (PBC).

Multiple drug candidates have entered clinical development, all filed for regulatory approval in both China and the United States. The core product, CS0159, is poised to enter Phase III clinical trials. Its successful development will not only bring new therapeutic hope to patients but also, as more pipeline products advance, enable the company to build a comprehensive treatment platform covering various metabolic diseases, with the aim of becoming one of the global leaders in this field.