Key Products

F351 (Hydronidone)

F351 is Gyre’s lead development candidate for the treatment of liver fibrosis that is being developed for two different indications. It is a structurally modified derivative of pirfenidone designed to optimize metabolic properties while targeting the TGF-β1 signaling pathway, a key mediator of fibrogenesis. Gyre is developing F351 for two primary indications: Chronic hepatitis B (CHB)-associated liver fibrosis in the PRC and MASH-associated liver fibrosis initially in the United States.

CHB-Associated Liver Fibrosis (PRC)

Liver fibrosis is a condition where healthy tissues in the liver become scarred in response to chronic inflammation. If left untreated, it can progress to cirrhosis—the final, severe stage where extensive scarring permanently distorts the liver’s architecture and significantly impairs its vital functions. Viral hepatitis is estimated to cause up to 50% of fibrosis and 65% cirrhosis worldwide. Without intervention, liver fibrosis and cirrhosis typically progress from manageable organ damage to systemic, life-threatening liver failure and hepatocellular carcinoma (HCC). No non-viral directed therapy has been shown to reduce fibrosis in viral induced hepatitis. F351 is a next-generation anti-fibrotic agent developed to address this unmet medical need. Mechanistically, F351 modulates key intracellular signaling pathways linked to fibrosis, and prevents the activation of hepatic stellate cells (HSCs)—the primary drivers of collagen deposition and fibrotic scarring in the liver. F351 offers an encouraging clinical profile characterized by enhanced potency and a favorable safety profile consistent with prior clinical experience. Based on these results, Gyre has filed a New Drug Application (NDA) with China’s National Medical Products Administration (NMPA).

MASH-Associated Liver Fibrosis (USA)

In addition to viral hepatitis, liver fibrosis and cirrhosis can be caused by a wide range of chronic injuries, including metabolic conditions, alcohol abuse, autoimmune responses, and genetic disorders. Globally, advanced liver fibrosis and cirrhosis affect an estimated 3.3% and 1.3% of the population, respectively. A primary contributor is Metabolic Dysfunction-Associated Steatohepatitis (MASH), a progressive liver disease caused by excess fat buildup triggering inflammation and cell damage. With a global adult prevalence of 5% to 6%, MASH has emerged as a leading driver of liver fibrosis and cirrhosis. Developing effective therapeutics for MASH-driven fibrosis and cirrhosis addresses a profound unmet medical need and represents a transformative clinical and commercial opportunity.

While the cause of the initial liver injury may vary, the progression from chronic liver injury to fibrosis and then to cirrhosis converges on a shared core molecular and cellular pathway. This process begins with initial hepatic damage to the activation of TGF-β signaling, which triggers HSCs to persistently produce and secrete collagen, leading to subsequent liver fibrosis. Preclinical studies demonstrate that F351 interrupts the injury-TGFβ-HSC-collagen cascade by downregulating TGF-β and profibrotic genes in HSC and inducing HSC apoptosis, as shown in preclinical models of toxin- and bile-induced liver fibrosis. Combined with its clinical success in HBV-related fibrosis, these results support F351’s potential to treat liver fibrosis and cirrhosis from diverse etiologies, such as MASH.

In the United States, Gyre has completed a Phase 1 clinical trial in healthy volunteers evaluating F351’s safety, tolerability, and PK. Gyre plans to file an Investigational New Drug (IND) application in the U.S. by the end of 2026, and, if the IND becomes effective, initiate a Phase 2 clinical trial.

F528

This molecule was discovered by Gyre using a rational design strategy to modify traditional macrolide compounds, selectively eliminating their antibacterial activity while preserving immunomodulatory properties. Through iterative medicinal chemistry optimization and screening, F528 was identified as a lead compound exhibiting potent anti-inflammatory effects with no detectable antibacterial activity.

Chronic Obstructive Pulmonary Disease (COPD)

COPD is the fourth leading cause of death worldwide, causing 3.5 million deaths in 2021, approximately 5% of all global deaths. The disease is characterized by persistent respiratory symptoms and progressive airflow limitation. Mechanistically, COPD drives a maladaptive wound-healing response leading to peribronchiolar fibrosis and the resulting accumulation of excess collagen narrows the small airways, directly contributing to permanent airflow obstruction. Current treatment options include long-acting bronchodilators and inhaled corticosteroids to manage airway constriction, and targeted immunomodulators and long-term macrolide antibiotics to reduce the frequency of acute exacerbations. However, these therapies cannot reverse established lung damage or halt disease progression and are often hampered by therapy resistance and the risks associated with chronic antibiotic exposure. Consequently, developing novel therapeutics to address these profound unmet needs represents a significant clinical and commercial opportunity.

Macrolide antibiotics, characterized by a large macrocyclic lactone ring, bind to 23S rRNA in the 50S subunit of the bacterial ribosome, thereby blocking bacterial protein synthesis and growth. Although macrolides have been used to treat respiratory infections since the 1950s, it was not until the late 1980s that their potent immunomodulatory properties were recognized, with their antibacterial effects being considered secondary in the management of COPD. Non-antibacterial macrolides represent a promising class of novel respiratory therapeutics, offering potent immunomodulatory benefits while mitigating the risks of antibiotic resistance and dysbiosis-related side effects. In multiple preclinical models of COPD, F528 demonstrated robust therapeutic efficacy, as evidenced by significant improvements in emphysema, airway inflammation, and lung function. Moreover, preclinical safety studies revealed a more favorable therapeutic window and improved safety profile compared with traditional antibiotics, supporting its potential as a first-in-class, non-antibacterial macrolide for the treatment of COPD. Gyre anticipates submitting an IND application for F528 in the first quarter of 2027.

CDK2-Cyclin E Dual Degrader for Cancers

The cell cycle is the fundamental process governing cellular growth, DNA replication, and division; its dysregulation is a hallmark of major human pathologies, most notably cancer.

The cell cycle process is tightly regulated by cyclin-dependent kinases (CDKs), a family of enzymes that remain catalytically inactive until bound to specific regulatory cyclins. In particular, the cyclin E-CDK2 complex serves as the critical G1/S switch, acting as a molecular gatekeeper to ensure DNA synthesis begins only when the cell is fully prepared for division. Elevated cyclin E—driven by gene amplification or protein overexpression—locks this switch in a constitutive “on” state, driving uncontrolled proliferation. This aberration is prevalent in several aggressive malignancies, including ovarian, endometrial, gastroesophageal, breast, and lung cancers, and serves as a primary mechanism of resistance to CDK4/6 inhibitors in HR+ HER2- breast cancer.

Developing specific, effective therapeutics targeting cyclin E-CDK2 addresses a profound unmet medical need and offers a paradigm-shifting opportunity for both clinical practice and the commercial market. To this end, Gyre is developing CG923308, a highly potent and selective dual degrader of CDK2 and cyclin E. In preclinical models characterized by cyclin E amplification or CDK4/6 inhibitor resistance, CG923308 demonstrated precise target degradation and outperformed leading late-stage clinical CDK2 inhibitors in blocking cell proliferation and achieving durable tumor suppression. Furthermore, CG923308 exhibits a favorable pharmacokinetic (PK) and safety profile. Gyre anticipates submitting an Investigational New Drug (IND) application for CG923308 in the first quarter of 2027.

TYK2-JAK1 Dual Degrader for Autoimmune Diseases

Autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), arise from systemic immune dysregulation that leads to chronic inflammation. This persistent inflammatory state triggers a maladaptive wound-healing response characterized by the excessive deposition of extracellular matrix components, leading to fibrosis and the progressive loss of organ function. Despite a rapidly evolving therapeutic landscape, a significant number of patients continue to experience inadequate disease control or treatment-limiting toxicities, highlighting a critical unmet medical need for therapies that target both inflammatory and fibrotic pathways.

Central to the pathogenesis of autoimmune diseases are the dysregulation of cytokine signaling pathways, particularly those mediated by the Janus kinase (JAK) family. JAK1 and TYK2 (Tyrosine Kinase 2) are two JAK family members that serve as critical intracellular transducers for various pro-inflammatory cytokine receptors. In many autoimmune disorders, aberrant JAK1 and TYK2 signaling drives a self-sustaining inflammatory feedback loop. While JAK1 is a primary mediator of the broad inflammatory cascades characteristic of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), TYK2 is more specifically implicated in the Type I interferon signatures and interleukin pathways that define lupus and psoriasis. Consequently, the selective targeting of these two kinases has emerged as a compelling therapeutic strategy for suppressing pathologic signaling while minimizing systemic side effects, with the potential to improve therapeutic outcomes in autoimmune diseases.

Gyre is developing CG620953, a highly potent and selective dual degrader of TYK2 and JAK1. In preclinical studies, CG920953 demonstrated selective target degradation and outperformed commercialized TYK2 and JAK1 selective inhibitors in reducing disease activity. CG620953 also exhibits a favorable pharmacokinetic (PK) and safety profile, providing rationale for further evaluation in the clinic. Gyre anticipates submitting an Investigational New Drug (IND) application for CG620953 in the first quarter of 2027.