May 22,2025  Hydronidone (F351) Phase 3 Trial in CHB-Associated Liver Fibrosis  - Topline Data Review  NASDAQ: GYRE 

 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 and uncertainties and are based on management’s estimates and assumptions. All statements, other than statements of historical facts included in this presentation, are forward-looking statements, including statements concerning: Gyre’s plans, objectives, goals, strategies, future events, or intentions relating to Gyre’s products and markets; the safety, efficacy and clinical benefits of Gyre’s product candidates; the anticipated timing and design of any planned or ongoing preclinical studies and clinical trials; Gyre’s research and development efforts; timing of expected clinical readouts, including timing of initiation of Gyre’s Phase 2 trial in the U.S. for F351 for the treatment of MASH-associated liver fibrosis, timing of completion of Gyre’s Phase 2 clinical trial in the PRC of F573 for ALF/ACLF, Gyre’s initiation of Phase 1 trial of F230 for the treatment of PAH and IND submission of F528 in COPD, the expectations regarding commercial launch of nintedanib and avatrombopag maleate tablets, management’s plans and objectives for future operations and future results of anticipated product development efforts; potential addressable market size; and Gyre’s liquidity and capital resources and business trends. In some cases, you can identify forward-looking statements by terms such as “believe,” “can,” “could,” “design,” “estimate,” “expect,” “forecast,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “objective,” “should,” “strategy,” “will,” “would,” or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors that could cause Gyre’s actual results to differ materially from the forward-looking statements expressed or implied in this presentation, such as the uncertainties inherent in the clinical drug development process, the regulatory approval process, the timing of any regulatory filings, the potential for substantial delays, the risk that earlier study results may not be predictive of future study results, manufacturing risks, and competition from other therapies or products, as well as those described in “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition” in Gyre’s Annual Report on Form 10-K for the year ended December 31, 2024 filed on March 17, 2025 with the Securities and Exchange Commission (the “SEC”) and elsewhere in such filing and in Gyre’s other periodic reports and subsequent disclosure documents filed with the SEC.  Gyre cannot assure you that it will realize the results, benefits or developments that it expects or anticipates or, even if substantially realized, that they will result in the expected consequences or affect Gyre or its business in the ways expected. Forward-looking statements are not historical facts, and reflect management’s current views with respect to future events. Given the significant uncertainties, you should evaluate all forward-looking statements made in this presentation in the context of these risks and uncertainties and not place undue reliance on these forward-looking statements as predictions of future events. All forward-looking statements in this presentation apply only as of the date made and are expressly qualified in their entirety by the cautionary statements included in this presentation. Gyre has no intention to publicly update or revise any forward-looking statements to reflect subsequent events or circumstances, except as required by law. Gyre obtained the data used throughout this presentation from its own internal estimates and research, as well as from research, surveys and studies conducted by third parties. Internal estimates are derived from publicly available information and Gyre’s own internal research and experience, and are based on assumptions made by management based on such data and its knowledge, which it believes to be reasonable. In addition, while Gyre believes the data included in this presentation is reliable and based on reasonable assumptions, Gyre has not independently verified any third-party information, and all such data involve risks and uncertainties and are subject to change based on various factors.  This presentation concerns a discussion of investigational drugs that are under preclinical and/or clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated.  2 

 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 without fibrosis progression at Week 52:    Hydronidone: 49.57% vs. Placebo: 34.82%    (P = 0.0246)  Favorable Safety Profile  Serious Adverse Events: 4.88% (6/123, Hydronidone) vs. 6.45% (8/124, Placebo)  No discontinuations due to adverse events  Clinical and Regulatory Pathways  Breakthrough Therapy Designation (China NMPA2, 2021), potentially first-in-class approval   New Drug Application (NDA) to NMPA expected in Q3 2025, with accelerated approval to be sought  U.S. IND filing for Phase 2 trial in MASH fibrosis expected in 3Q 2025; trial initiation planned for 2H 2025  1. ITT = Intent-To-Treat. 2. NMPA = National Medical Products Administration of China 

 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  Key Exclusion Criteria  Statistical Method  Age: 18–65, CHB with significant fibrosis (Ishak ≥3)  Positive HBV-DNA; ALT < 8× ULN  No antiviral, antifibrotic herbal meds within 3 months  Decompensated cirrhosis, liver cancer suspicion, BMI > 30  GI bleeding, high bilirubin/AFP, platelet ≤60×10⁹/L  Hepatitis C or non-viral hepatitis, serious comorbidities  Pregnancy or recent participation in other trials  Sample size: 248 patients (1241 per arm)  Efficacy evaluated in ITT and PPS population using χ² test, Wilcoxon rank-sum test, and ANCOVA.  1. One patient in the Hydronidone treatment group did not receive any dose of the study medication and was therefore excluded from the final analysis. 

 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 decrease in the Ishak stage score of liver fibrosis ≥ 1 after 52 weeks of treatment compared to baseline.  Key Secondary Endpoint:  A decrease in liver inflammation grade by ≥1 after 52 weeks of treatment relative to baseline, without progression of fibrosis (Scheuer score).  Assessment:  Liver biopsies at baseline and week 52; read independently by three blinded expert pathologists.  Wk 0  Wk 4  Wk 8  Wk 12  Wk 24  Wk 36  Wk 52  Regular follow-ups   Liver Biopsy  Liver Biopsy  1. The trial initially planned for 44 hospital centers. 39 were activated, and 35 ultimately enrolled patients, reflecting common variability in multicenter trial execution. 

 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 (35.03)  54.76 (44.32)  Total Bilirubin (TBIL), mean (SD), µmol/L  15.66 (6.20)  16.39 (7.72)  HBV DNA, log10 IU/mL, mean (SD)  4.82 (1.94)  5.24 (1.92)  HBeAg Positive, n (%)  42 (34.15)  49 (39.52)  FibroScan LSM, mean (SD), kPa  12.87 (6.19)  12.85 (6.51)  On Entecavir at Baseline, n (%)  123 (100%)  124 (100%)  Baseline Demographics  6 

 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  Included in PPS (per-protocol)  115  112  Patient Disposition  7 

 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 = 123  N = 124  Primary endpoint achieved  +23.0% treatment delta vs. placebo  Highly statistically significant (p=0.0002)  Consistent with fibrosis regression rates observed in Phase 2  Note: P = 0.0002 (Cochran-Mantel-Haenszel test). 95% CI based on Newcombe-Wilson method. Trial was designed to detect ≥20% absolute delta in fibrosis regression at 52 weeks. 

 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%  33.87%  33.87%   Grade ≥3 ADRs  1.63%  1.63%  1.61%  1.61%   Discontinuation due to AE  0  0  0  0   Temporary interruption due to AE  0  0  0.81%  0.81%   Dose reduction due to AE  0  0  0  0   Any SAE  6 (4.88%)  6 (4.88%)  8 (6.45%)  8 (6.45%)   Due to Investigational Drug:   Possibly unrelated  2  3   Unrelated  4  5   Death  0  0  Safety Profile  9 

 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/poisoning/complications  Radius Fracture  1  0  Humerus Fracture  1  0  Infections and Infestations  Infectious Pneumonia  1  0  Upper Respiratory Infection  0  1  All SAEs were assessed to be unrelated to the investigational drug (Hydronidone).  No discontinuations due to SAEs across either treatment arm​.  Summary of all Serious Adverse Events (SAEs)  10 

 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 (including cysts and polyps)   Benign Epididymal Neoplasm  0  1  Cardiac disorders   Arrhythmia  0  1  TOTAL  9  8  Summary of all Serious Adverse Events (SAEs cont’d)  11 

 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 improvement without progression of fibrosis at Week 52  (ITT analysis)  N = 123  N = 124  Statistically significant (p=0.0246)  +14.75% treatment delta vs placebo  Reinforces anti-inflammatory activity  Note: Additional secondary endpoints were evaluated but are not shown here as they were not the focus of this topline announcement.  Note: P = 0.0246 (Cochran-Mantel-Haenszel test). 95% CI based on Newcombe-Wilson method. This was a secondary endpoint without pre-specified power; interpretation is exploratory. 

 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 Opportunity  In the U.S., the MASH fibrosis market is approximately 7.2 times larger than the CHB fibrosis market.  Clinical Rationale  Hydronidone modulates TGF-β / p38γ / Smad7 signaling pathway — directly targeting fibrosis progression and offering a differentiated approach from metabolic agents.  Regulatory Pathway  Hydronidone’s CHB data helps to reduce risks in MASH development and potentially supports accelerated regulatory review and fast track.  Competitive Differentiation  Hydronidone’s unique anti-fibrotic approach positions it as a complementary therapy — not a competitor — to metabolic agents like THR-β, GLP-1s, and FGF21. 

 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 & Smad7  Rationale for MASH expansion: Hydronidone targets the same core fibrotic biology - TGF-β, p38γ, and Smad7 - underlying both CHB and MASH, providing a mechanistically de-risked path into MASH. 

 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  Attribute  Pirfenidone  Hydronidone   Benefit  Structure  Parent compound  Analog with –OH group  ↑ Smad7  MoA  TGF-β  TGF-β + p38γ + Smad7  ↑ Potency  Metabolism  Phase I (oxidation)  Phase II (conjugation)  ↓ Toxicity  Hepatic Safety  Known liver risk  Improved  ↑ Tolerability  MASH Evidence  Some benefit (PROMETEO, model)2  Strong effect in a validated preclinical model  ↑ Rationale  1. Phase II metabolism is associated with improved hepatic safety due to faster detoxification.. 2. González-Huezo M, et al. Real-life proof-of-concept trial of prolonged-release pirfenidone in advanced liver fibrosis (PROMETEO study). Hepatol Int. 2021;15(2):377–388.  Hydronidone enhances pirfenidone’s anti-fibrotic effect by also inhibiting p38γ and upregulating Smad7, improving hepatic safety and supporting its expansion into metabolic liver diseases like MASH. 

 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  Prominent ballooning  Mild improvement  Moderate to marked improvement  NASH Score  Elevated NAS score  Partial improvement in NAS score  Substantial improvement in NAS score  Hydronidone reduced fibrosis and ballooning in a dose-dependent manner.  Outperformed Pirfenidone in the model, demonstrating superior potency in fibrosis reversal.  Validates anti-fibrotic activity in a metabolic disease setting, supporting MASH expansion.  Note: 100 mpk not shown due to plateaued efficacy or potential toxicity. Study conducted in a CCl₄ + HFD-induced NASH model using histology-based endpoints (fibrosis, ballooning, NAS). Full scientific package available upon request. 

 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 HIGH  Resolve steatohepatitis  Prevent fibrosis progression  Prevent progression to cirrhosis  Prevent decompensation  Metabolic drugs / obesity drugs  Metabolic + anti-fibrotic drugs  Potent anti-fibrotic + metabolic  Potent anti-fibrotic therapies  Hydronidone Primary Target 1  1. We estimate ~650K compensated F2–F4 MASH patients in the U.S., based on market data and internal modeling. F351 is expected to target the full group, with a core focus of ~450K patients, excluding low-risk F2s and prioritizing the top 15–20% of F2s with progressive fibrosis. 

 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  MOA  TGF-β   THR-β  THR-β  FGF21   FGF21   GIP/GLP-1   GLP-1  GLP-1/glucagon  Population  ITT  ITT  ITT  ITT  ITT  ITT  ITT  Modified ITT  ITT  N (Active/Placebo)  123/124  ~319/~309  44/41  43/43  63/61  81/45  219/219  80/80  77/77  Total ITT  248  966  181  126  181  192  659  320  295  Focus  F2 - F4  F2 - F3  F2 - F3  F2 - F3  F4  F2 - F3  F2 - F3  F2 - F3  F2 - F3  Duration  52 wks  52 wks  52 wks  96 wks  24 wks  52 wks  72 weeks  46 weeks  Fibrosis Improvement  52.9%  ~26%  56.8%  49%  29%  27%  54.9%  43%  36%  Placebo  29.8%  ~10%  34.1%  19%  12%  7%  29.7%  33%  22%  Placebo-Adjusted  +23.0%  +16%  +22.7%  +30%  +17%  +20%  +25.2%  +10%  +14%  Note: This illustrative comparison includes data from distinct disease settings (CHB and MASH). While fibrosis is a shared endpoint, differences in etiology, pathophysiology, and trial design limit direct comparability. Cross-indication interpretation is hypothetical and does not imply therapeutic equivalence.  Rezdiffra (Madrigal) sets the benchmark as the first FDA-approved therapy for MASH.  Hydronidone offers a fibrosis-first approach, acting directly on fibrotic tissue, and is the only agent with a demonstrated focus on F4 (cirrhotic) patients.  Hydronidone is designed to be complementary, not competitive — potentially used as an add-on alongside metabolic agents.  Our regulatory aim is to establish a new standard for direct fibrosis reversal in MASH patients.  Comparator data sourced from published studies and company press releases (e.g., Madrigal, Viking, Akero, 89bio, Lilly, Novo Nordisk, Boehringer Ingelheim). Differences in disease, design, and population limit direct comparison.  

 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 improvement without fibrosis progression: Hydronidone: 49.57% vs. Placebo: 34.82% (P = 0.0246)  Reinforces anti-inflammatory activity  Favorable Safety Profile  Serious Adverse Events: 4.88% (6/123, Hydronidone) vs. 6.45% (8/124, Placebo)  No discontinuations due to adverse events; All SAEs were assessed to be unrelated to Hydronidone  Key Next Steps  Received Breakthrough Therapy Designation from China NMPA in 2021; potential first-in-class approval - Gyre’s second, following Pirfenidone in 2011.  NDA submission to NMPA expected in Q3 2025, seeking accelerated approval based on positive Phase 3 results.  IND filing for MASH-associated liver fibrosis planned for Q3 2025; pending FDA clearance, Phase 2 trial expected to begin in 2H 2025. 

 21  APPENDIX: Clinical Trial - Common Adverse Events Detail    &   F351 - Mechanism of Action  

 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 events (≥5% Incidence)  No major safety signal emerged throughout the 52-week treatment period.  Adverse events were balanced between Hydronidone and placebo groups.  Most events were mild and not treatment-limiting.  No increases in pruritus, hepatotoxicity, or lipid-related abnormalities. 

 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 isoform plays a pivotal role in TGF-β-stimulated collagen production. F351 attenuates fibrosis, at least in part, by targeting the p38 MAPK transduction pathway.  During hepatic injury, TGF-β upregulation triggers hepatic stellate cell (HSC) activation and differentiation into myofibroblasts. This phenotypic transformation is characterized by cytoskeletal remodeling, including α-smooth muscle actin (α-SMA) expression, which serves as a specific marker for myofibroblasts and the onset of fibrogenesis.  Extensive preclinical and clinical studies indicate that activated myofibroblasts with elevated α-smooth muscle actin (α-SMA) expression serve as the dominant producers of fibrillar collagen and key ECM proteins, thereby driving hepatic fibrogenesis.  Liver Injury → TGF-β ↑ triggers multiple fibrosis pathways: 1. → p38γ → HSC Activation → α-SMA ↑ → ECM Accumulation → Fibrosis 2. → Smad2/3 (phosphorylation) → Fibrosis 3. ⊣ Smad7 (inhibitory) → Upregulation of TGF-beta signaling → Activation of both p38gamma and SMAD2/3 cascades 

 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 therapeutic strategies to fight liver fibrosis  24  Xu, Xianjun et al. “Hydronidone ameliorates liver fibrosis by inhibiting activation of hepatic stellate cells via Smad7-mediated degradation of TGFβRI.” Liver international : official journal of the International Association for the Study of the Liver vol. 43,11 (2023): 2523-2537. doi:10.1111/liv.15715  TGF-β plays important role in liver fibrosis by activating HSCs 

 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.  25  Animal studies demonstrated Hydronidone upregulated the expression of Smad7 and inhibited phosphorylation of Smad2/3 

 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 prevent the formation of active metabolites and covalent binding to proteins, suggesting a mechanistic basis for hydronidone’s improved hepatic safety profile compared with Pirfenidone.  Phase II metabolism  Phase I metabolism  Optimization  Achieve higher P38γ binding affinity  Pirfenidone  Hydronidone  Kinase Inhibition Profile  In vitro kinase assay shows that both hydronidone and Pirfenidone effectively inhibit p38γ activity, with hydronidone exhibiting a higher inhibition potency than Pirfenidone.  These findings indicate that hydronidone exhibits stronger inhibition of the p38γ pathway, potentially contributing to its enhanced antifibrotic activity. 

 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 metabolism, known for safer detoxification and fewer reactive byproducts  Primarily metabolized through Phase I oxidation (CYP1A2), which can generate reactive metabolites  Liver Safety  Designed to reduce hepatotoxicity; favorable liver safety profile in trials  Observed increases in liver enzymes in some patients; rare hepatic events documented  Fibrosis Efficacy (in humans)  Shown to reverse fibrosis in 55% of patients with CHB (270 mg group)1  Exploratory clinical data in liver fibrosis; not approved for fibrotic liver disease  1. Cai et al. Clin Gastroenterol Hepatol. 2023;21(7):1893–1901. doi:10.1016/j.cgh.2022.05.056 

 28  Thank you  Contact:  David Zhang  David.Zhang@Gyretx.com