Slide 1: Hydronidone (F351) Phase 3 Trial in CHB-Associated Liver Fibrosis - Topline Data Review
May 22,2025 Hydronidone (F351) Phase 3 Trial in CHB-Associated Liver Fibrosis - Topline Data Review NASDAQ: GYRE
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the federal securities laws regarding the current plans, expectations and strategies of Gyre Therapeutics, Inc. and its subsidiaries (“Gyre”), which statements are subject to substantial risks an
Slide 3: Summary of Topline Results
3 Summary of Topline Results Primary Endpoint Met with High Statistical Significance ≥1-stage fibrosis regression at Week 52: Hydronidone: 52.85% vs. Placebo: 29.84% (P = 0.0002; ITT1 analysis with central blinded pathology review) Key Secondary Endpoint Achieved ≥1-grade inflammation improvement wi
Slide 4: Phase 3 Clinical Trial Overview
4 Phase 3 Clinical Trial Overview Objective: To evaluate the efficacy and safety of Hydronidone (270 mg/day) - the most effective dose identified in the Phase 2 study - in combination with Entecavir for the treatment of liver fibrosis associated with chronic hepatitis B (CHB) Key Inclusion Criteria
Slide 5: Phase 3 Trial Design: CHB-Associated Liver Fibrosis
5 Hydronidone: 270mg/day + Entecavir 0.5mg/day Placebo: Matching placebo capsules + Entecavir 0.5mg/day R1:1 Phase 3 Trial Design: CHB-Associated Liver Fibrosis 52-week, multicenter, double-blind, placebo-controlled (39 sites1 in China) Primary Endpoint: Efficacy of fibrosis reversal, defined as a d
Slide 6: Baseline Demographics
Baseline Characteristic Hydronidone (N=123) Placebo (N=124) Age, mean (SD), years 44.24 (10.30) 44.25 (10.24) Male, n (%) 87 (70.7) 98 (79.03) Female, n (%) 36 (29.27) 26 (20.97) BMI, mean (SD), kg/m² 24.05 (3.01) 23.58 (3.06) ALT, mean (SD), U/L 59.37 (55.74) 68.43 (62.43) AST, mean (SD), U/L 48.74
Slide 7: Patient Disposition
Patient Status Hydronidone (N=123) Placebo (N=124) Randomized 124 124 Received at least 1 dose 123 124 Completed 52 weeks of treatment 118 116 Discontinued early 6 8 – Due to AE 0 0 – Lost to follow-up 1 1 – Withdrew consent 4 7 – Other (e.g., protocol deviation) 1 0 Included in ITT analysis 123 124
Slide 8: Primary Endpoint Met with Statistically Significant Fibrosis Regression
8 Primary Endpoint Met with Statistically Significant Fibrosis Regression Hydronidone Placebo 52.85% 29.84% 0 10 P = 0.0002 % patients with ≥1-stage fibrosis regression at week 52 20 30 50 40 Treatment Delta 23.01% (95% CI: 10.75% – 34.32%) ≥1-stage Fibrosis Regression at Week 52 (ITT analysis) N =
Slide 9: Safety Profile
Safety Event Hydronidone (N=123) Hydronidone (N=123) Placebo (N=124) Placebo (N=124) Any TEAE 98 (79.67%) 98 (79.67%) 103 (83.06%) 103 (83.06%) Grade 1 AEs 27.64% 27.64% 33.06% 33.06% Grade 2 AEs 43.90% 43.90% 43.55% 43.55% Grade ≥3 AEs 8.13% 8.13% 6.45% 6.45% Drug-related AEs (ADRs) 32.52% 32.52% 3
Slide 10: Summary of all Serious Adverse Events (SAEs)
System Organ Class Preferred Term Hydronidone (N=123) Placebo (N=124) All SAEs 6 (4.88%) / 9 cases 8 (6.45%) / 8 cases Gastrointestinal Disorders Ascites 2 0 Hemorrhoids 1 0 Inguinal Hernia 0 1 Musculoskeletal Disorders Carpal Tunnel Syndrome 1 0 Disc Herniation 1 0 Spondyloarthritis 0 1 Injury/pois
Slide 11: Summary of all Serious Adverse Events (SAEs cont'd)
System Organ Class Preferred Term Hydronidone (N=123) Placebo (N=124) Renal and Urinary Disorders Nephrolithiasis 0 1 Renal Cyst 0 1 Respiratory, Thoracic and Mediastinal Disorders Pulmonary Mass 1 0 Hepatobiliary Disorders Cholestatic jaundice 0 1 Neoplasms benign, malignant and unspecified (includ
Slide 12: Key Secondary Endpoint Met: Significant Reduction in Liver Inflammation
12 Key Secondary Endpoint Met: Significant Reduction in Liver Inflammation Hydronidone Placebo 49.57% 34.82% 0 10 P = 0.0246 % patients with ≥1-grade inflammation improvement without fibrosis progression at week 52 20 30 50 40 Treatment Delta 14.75% (95% CI: 1.90% – 26.91%) ≥1-Grade inflammation imp
Slide 13: Expanding Hydronidone's Potential: From CHB Fibrosis in China to MASH in the U.S.
13 Expanding Hydronidone’s Potential: From CHB Fibrosis in China to MASH in the U.S. 1. Based on analysis of third-party epidemiological research, published academic studies, and internal modeling. Compensated F2-F4 MASH diagnosed population: ~650K1 CHB diagnozed population: ~ 90K1 Market Opportunit
Slide 14: CHB and MASH Share Common Fibrotic Signaling Pathway
14 CHB and MASH Share Common Fibrotic Signaling Pathway CHB- Associated Liver Fibrosis MASH- Associated Liver Fibrosis Etiology Viral (HBV) Metabolic (Obesity, T2 diabetes) Fibrosis Driver Target Cell Type F351 Mechanism TGF-β / p38γ / Smad7 Hepatic Stellate Cells Anti-fibrotic via TGF-β, p38γ & Sma
Slide 15: Hydronidone is Purpose-Built on Pirfenidone's Foundation
Hydronidone is Purpose-Built on Pirfenidone’s Foundation - with Enhanced Potency and Safety 15 Pirfenidone → [Structural Analog + Hydroxyl Group] → Hydronidone ↓ ↓ Modest Liver Activity Enhanced Smad7 Upregulation + Phase II Metabolism 1 ↑ Hepatotoxicity → ↓ Hepatotoxicity + ↑ Anti-fibrotic Potency
Slide 16: Hydronidone Demonstrates Dose-Dependent Anti-Fibrotic Efficacy in Preclinical MASH Model
Hydronidone Demonstrates Dose-Dependent Anti-Fibrotic Efficacy in Preclinical MASH Model 16 Vehicle Hydronidone-15mpk Hydronidone-50mpk Endpoint Vehicle Hydronidone (15 mpk) Hydronidone (50 mpk) Fibrosis Extensive fibrosis Moderate reduction in fibrosis Marked reduction in fibrosis Ballooning Promin
Slide 17: Hydronidone Targets Fibrosis Specifically for Advanced MASH
17 Hydronidone Targets Fibrosis Specifically for Advanced MASH FIBROSIS STAGING Risk Staging based on: Fibrosis Progression Liver Events CV Events Primary Treatment Objectives: Improve glycemic control Improve dyslipidemia Reduce weight Primary Therapeutic Options F1 F2 F3 F4 LOW MEDIUM HIGH VERY HI
Slide 18: Meaningful Fibrosis Regression Observed in Ishak (F4) Patients in Two Independent Trials
Meaningful Fibrosis Regression Observed in Ishak 6 (F4) Patients in Two Independent Trials Subgroup-based analysis; not powered for statistical significance.(Biopsy-confirmed results from 52-week, randomized, double-blind trials with blinded reads by independent pathologists) Phase 2: • 36% (5/14) o
Slide 19: Positioning Hydronidone In The Evolving MASH Treatment Landscape
19 Positioning Hydronidone In The Evolving MASH Treatment Landscape t ORAL INJECTABLE Hydronidone Rezdiffra VK2809 EFX Pegozafermin Tirzepatide Semaglutide Survodutide Indication CHB MASH MASH MASH MASH MASH MASH MASH Study Phase Phase 3 Approved Phase 2b Phase 2b Phase 2b Phase 2b Phase 2 Phase 2 M
Slide 20: Key Takeaways and Next Steps
20 Key Takeaways and Next Steps Primary Endpoint Met with High Statistical Significance ≥1-stage fibrosis regression at Week 52: Hydronidone: 52.85% vs. Placebo: 29.84% (P = 0.0002) Consistent with fibrosis regression rates observed in Phase 2 Key Secondary Endpoint Achieved ≥1-grade inflammation im
Slide 21: APPENDIX: Clinical Trial - Common Adverse Events Detail & F351 - Mechanism of Action
21 APPENDIX: Clinical Trial - Common Adverse Events Detail & F351 - Mechanism of Action
Slide 22: Most common adverse events (≥5% Incidence)
Preferred Term Hydronidone (%) Placebo (%) Upper Respiratory Tract Infection 25 (20.33) 21 (16.94) COVID-19 14 (11.38) 8 (6.45) Urinary Tract Infection 10 (8.13) 7 (5.65) Hyperlipidemia 12 (9.76) 13 (10.48) Hepatic Steatosis 8 (6.50) 12 (9.68) Liver pain 8 (6.50) 8 (6.45) 22 Most common adverse even
Slide 23: Comparison of Hydronidone and Pirfenidone metabolism
23 Comparison of Hydronidone and Pirfenidone metabolism Hepatic cell Hepatic stellate cell Myofibroblasts Liver fibrosis Activation As a key profibrotic cytokine, TGF-β drives hepatic stellate cell (HSC) activation, promotes extracellular matrix (ECM) deposition, and triggers fibrogenesis. The p38γ
Slide 24: TGF-β plays important role in liver fibrosis by activating HSCs
Smad7 is a negative regulator of TGF-β signaling. Smad7 knockdown can promote HSC activation and liver fibrosis. Smad7 overexpression can prevent liver fibrosis. Hydronidone is believed to effectively target this pathway. Inhibiting HSC activation is believed to be one of the most effective therapeu
Slide 25: Animal studies demonstrated Hydronidone upregulated Smad7 expression
Smad7 is a known negative regulator of liver fibrosis, suggesting clinical potential in a recognized cascade Note: Statistical significance: *p < .05, **p < .01, *p < .001 (one-way ANOVA with post hoc tests). Data from Xu et al., Liver International (2023), 43(11): 2523–2537. doi:10.1111/liv.15715.
Slide 26: Hydronidone vs. Pirfenidone: Mechanistic and safety advantages
26 Hydronidone vs. Pirfenidone: Mechanistic and safety advantages The introduction of a hydroxyl group shifts its metabolic profile from Pirfenidone’s dominant Phase I oxidation to preferential Phase II conjugation (M3/M4 metabolites). Phase II metabolism, known as “detoxification metabolism,” can p
Slide 27: Hydronidone shaping up to be Pirfenidone 2.0
27 Hydronidone shaping up to be Pirfenidone 2.0 Feature Hydronidone Pirfenidone Mechanism of Action Tri-pathway mechanism: inhibits p38γ, upregulates Smad7, and suppresses TGF-β/Smad2/3 signaling Broadly downregulates TGF-β levels, with less defined pathway specificity Metabolism Undergoes Phase II
Slide 28: Thank you
28 Thank you Contact: David Zhang David.Zhang@Gyretx.com