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A Fully-Integrated Biopharmaceutical Company Focused on Fibrosis, Inflammatory
This presentation contains "forward-looking statements" within the meaning of
the federal securities laws, including Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, regarding the current plans, expectations and strategies of Gyre
Therapeutics, Inc. ("Gyre") and its subsidiaries, including Cullgen Inc. ("Cullgen"), 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 Gyre's ability to leverage China operations for discovery, validation and development of therapeutics, clinical development plans,
anticipated timelines and milestones of CG923308, F528, CG620953, F351, CG001419, CG009301, and ETUARYTM, including anticipated regulatory submissions and approvals, and the potential therapeutic benefits, efficacy, safety and differentiation
of such product candidates, and market size and commercial opportunity estimates. Gyre or Cullgen's plans, objectives, goals, strategies, future events, or intentions relating to Gyre or Cullgen's products and markets, the safety, efficacy
and clinical benefits of Gyre or Cullgen's product candidates, the anticipated timing and design of any planned and ongoing preclinical studies and clinical trials, Gyre or Cullgen's research and development efforts, plans and objectives of
management for future operations and future results of anticipated product development efforts, potential addressable market size and Gyre or Cullgen's liquidity and capital resources and business trends. In some cases, you can identify
forward-looking statements by terms such as "believe," "can," "could," "anticipate", "design," "estimate," "expect," "forecast," "intend," "may," "might," "plan," "target", "potential," "predict," "objective," "should," "strategy," "will,"
"would," "forthcoming," or the negative of these terms, and similar expressions that are predictions of or indicate future events and future trends. These forward-looking statements may include express or implied statements relating to: the
estimated future financial performance and financial position of Gyre; the synergies that may be achieved between Gyre and Cullgen; the therapeutic potential and utility, efficacy and clinical benefits of the product candidates of the
combined company, including for the treatment of fibrosis, pain and solid tumors; the risk/benefit profile of the product candidates of the combined company; expectations regarding Gyre or Cullgen's research and development efforts, including
timing of initiation of Phase 2 trials for the product candidates of the combined company; Gyre or Cullgen's expectations regarding the advancement of product candidates into IND-enabling studies; and Gyre and Cullgen's expectations, hopes,
beliefs, intentions and strategies; and other statements that are not historical fact. These statements involve known and unknown risks, uncertainties and other factors that could cause Gyre or Cullgen's actual results to differ materially
from the forward-looking statements expressed or implied in this presentation, in addition to those risks and uncertainties, 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, competition from other therapies or products and the impacts of
current macroeconomic and geopolitical risks. A discussion of these and other factors, is set forth in Gyre's Annual Report on Form 10-K for the year ended December 31, 2025 filed with the Securities and Exchange Commission (the "SEC") on
March 13, 2026 and elsewhere in such other filings and in Gyre's periodic reports and subsequent disclosure documents filed with the SEC. Each of Gyre and Cullgen 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 consequences or affect Gyre or Cullgen or its business in the way 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 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 and Cullgen have no intention to publicly update or revise any forward-looking statements to reflect subsequent events or circumstances, except as required by law. Certain information contained in this presentation and
statements made orally during this presentation relate to or is based on studies, publications, surveys and other data obtained from third-party sources and Gyre or Cullgen's own internal estimates and research. While each of Gyre and Cullgen
believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness
of, any information obtained from third-party sources. In addition, no independent sources have evaluated the reasonableness or accuracy of Gyre or Cullgen's internal estimates or research, and no reliance should be made on any information or
statements made in this presentation relating to or based on such internal estimates and research. This presentation contains, trademarks, trade names and service marks of other companies which are the property of their respective owners.
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. Forward-looking Statements
Gyre Therapeutics (Nasdaq: GYRE): At-A-Glance Following Recent Acquisition of
Cullgen Pipeline ranges from discovery stage to marketed products with programs covering multiple therapeutic areas including fibrosis, inflammatory diseases and cancer ~740 Employees WW ~170 R&D ~85 Manufacturing ~370 Sales &
Marketing ~115 G&A Combined entity intends to leverage established and cost-efficient China operations for accelerated discovery, early validation, and development of next generation therapeutics based on degraders and DACs San Diego,
CA Corporate HQ - G&A, Clinical Development Shanghai, China Drug Discovery, Clinical Development Beijing, China Manufacturing, Clinical Development and Commercialization
China Innovation and Validation Engine: Driving Strategic Value and
Efficiency Fibrosis, Inflammatory Diseases, Cancer Portfolio Based on US-China Innovation F528 Chronic Obstructive Pulmonary Disease (COPD) CG923308 CDK2/Cyclin E Degrader for Solid Cancers IND Enabling Phase 1 Phase 2 Phase 3 NDA
Filed Marketed ETUARY (pirfenidone) Radiation Induced Lung Injury (Phase 2/3)Line Extension CG620953 TYK2/JAK1 Degrader for Inflammatory Diseases F351 (hydronidone) CHB-associated Liver Fibrosis F351
(hydronidone) MASH-Associated Liver Fibrosis ETUARY (pirfenidone) Idiopathic Pulmonary Fibrosis (IPF) ETUARY (pirfenidone) Pneumoconiosis Line Extension Degrader Efficient and cost-effective operations accelerate new
pipeline development and indication expansion Inflammatory Diseases Cancer Pain Others New Molecule Discovery and Optimization Target Validation Clinical Validation
Gyre's ETUARY is the Market Leader of Pirfenidone for Treatment of Organ
First Product ETUARY Demonstrates Gyre's Capability from Innovation to
Commercialization and Managing Life Cycle of Innovative Drugs Third party pirfenidone sales outside of China fell substantially during same period and never recovered due to generic competition. Upcoming line extensions for ETUARY are
expected to catalyze sales growth
Promising Preclinical and Clinical Results for Two ETUARY Line
ExtensionsPotential to Drive Market Expansion Ref 1. Bai et al. (2025) https://pubmed.ncbi.nlm.nih.gov/39546810/ Ref 2. Hou et al (2025) https://pubmed.ncbi.nlm.nih.gov/41207313/ B. A phase 2 trial demonstrates efficacy of Etuary in
treating radiation-induced lung injury (RILI)2 A. Preclinical studies demonstrate efficacy of Etuary in treating pneumoconiosis1 Gross Vital Capacity Gas Transfer Efficiency Airway Resistance / Flow BIBF: nintedanib; DLCO: Diffusing
Capacity of the Lung for Carbon Monoxide ; IC: Inspiratory Capacity; FEV: Forced Expiratory Volume; FVC: Forced Vital Capacity; PFD: Pirfenidone; Si: Silicosis Operating Lung Volume Gross Vital Capacity Airway Resistance / Flow
F351 (hydronidone) A Next Generation Liver Fibrosis Therapy
F351 (hydronidone): An NDA Stage Next-Generation Fibrosis Therapy Primary
Indication Liver fibrosis caused by Chronic Hepatitis B (CHB) and Metabolic dysfunction-Associated Steatohepatitis (MASH) Summary Next-Generation Pirfenidone: An Antifibrotic Agent with Enhanced Potency, Improved Safety, and Favorable
Metabolism. Clinical Rationale F351 modulates the Smad7-TGF- and p38 signalling pathways, preventing the activation of hepatic stellate cells (HSCs)-the primary drivers of collagen deposition and fibrotic scarring in the liver. F351 will
be positioned as a complementary therapy to agents targeting metabolic drivers of fibrosis such as agonists of GLP-1 and THR- receptors and FGF21 analog. Current Status Phase 3 trial of CHB-associated liver fibrosis was completed in China;
Last patient completed treatment Oct 2024; Reported positive topline data in Q2 2025 - met primary endpoint. NDA accepted by NMPA in May 2026 Regulatory Breakthrough Therapy designation from NMPA (March 2021) for CHB-induced liver fibrosis
by NMPA and CDE. U.S. IND for MASH filed, with anticipated Phase 2 start in 2027. Opportunity China: Largest burden of hepatitis B world-wide, with an estimated 79 - 86 million cases of chronic HBV infections1 USA: 14.9 million MASH
patients in 2020 and increases to 23.2 million by 20502 F351 Upregulates Smad7, Downregulates TGF- receptor I, and Reduces Collagen Secretion3,4 Phase 3 China Positive Phase 3 topline results in CHB-associated liver fibrosis. NDA
accepted by China NMPA in May 2026 Phase 1 China & USA Well tolerated as a single agent and upon repeated oral dosing, with no SAEs reported. Consistent safety and PK profile in US trial Phase 2 China Met primary endpoint of
improvement of liver fibrosis score (Ishak decrease of 1 point) Good tolerability The 90 mg/tid dose selected for Phase 3 F351 Development
Highlights https://pmc.ncbi.nlm.nih.gov/articles/PMC11806133/ https://pubmed.ncbi.nlm.nih.gov/39821400/ Xu et al (2023) PMID:37641479 Internal unpublished results
F351 Phase 3 Results Demonstrate New Global Potentialin Liver Fibrosis and
Cirrhosis 1-stage fibrosis regression at Week 52: F351: 52.85% (n=123) vs. Placebo: 29.84% (n=124) Delta: 23.01% p = 0.0002 (ITT1 analysis with central blinded pathology review) Consistent with fibrosis regression rates observed in
Phase 2 Primary Endpoint Met with High Statistical Significance 1-grade inflammation improvement without fibrosis progression at Week 52: F351: 49.57% (n=123) vs. Placebo: 34.82% (n=124) Delta: 14.75% p = 0.0246 Reinforces
anti-inflammatory activity Key Secondary Endpoint Reduction in Liver Inflammation Favorable SafetyProfile 1-stage fibrosis regression at Week 52: F351: 52.85% (n=123) vs. Placebo: 29.84% (n=124) Delta: 23.01% p = 0.0002 (ITT1
analysis with central blinded pathology review) Consistent with fibrosis regression rates observed in Phase 2 NDA accepted by NMPA in May 2026 Breakthrough Therapy Designation Priority Review of NDA (China NMPA, 2021, 2026)
U.S. MASH Fibrosis Market Provides Significant Opportunity for F351China First
Strategy Provides Accelerated POC USA MASH Therapeutics Sales forecast from Evaluate Pharma as of 5-13-2026 Assumes 50% of all MASH patients progress to MASH fibrosis (Stage F2) based on Luthra & Sheth (2025). 1 Le et al. (2025) JAMA;
AJMC; MASH Awareness; Estes et al. (2018) AASLD; L.E.K. interviews Current U.S. MASH prevalence is estimated at ~14 million1 MASH represents tremendous growth opportunity due to very low current MASH diagnosis rate (5-10%) Rising obesity
and diabetes increase MASH progression via liver inflammation 42% CAGR (2025 - 2032) Forecasted Market Size of MASH Fibrosis Therapies in the USA ($M USD)
Promising Path for FutureGrowth: Targeted Protein Degraders (TPDs) and
Degrader-Antibody Conjugates (DACs) Pipeline CDK2 - Cyclin E Dual-Degrader for Solid Tumors TYK2 - JAK1 Dual-Degrader for Inflammatory Diseases
13 CDK2 - Cyclin EDual-Degraderfor Solid Tumors
Hyperactivation of the CDK2-Cyclin E Complex Drives Solid Tumor Progression and
Confers Resistance to Breast Cancer Therapy A. CDK2-cyclin E promotes cell proliferation and cancer development B. Cyclin E is frequently amplified across multiple cancer types D. Diverse CDK4/6i resistance converge on activation of
CDK2/cyclin E Analyzed by cbioportal (TCGA, PanCancer) CDK2-cyclin E dual degrader blocks feedback induction of cyclin E by CDK2 inhibition and achieves sustained suppression of cell proliferation [1] Turner NC (2019) J Clin Oncol. PMID:
30807234 [2] Herrera-Abreu MT (2016) Cancer Res. PMID: 27020857 [3] Costa C (2020) Cancer Discov. PMID: 31594766 [4] Freeman-Cook (2021) Cancer Cell. PMID: 34520734 [5] Wander SA (2020) Cancer Discov. PMID: 32404308 CCNE1
overexpression Rb loss PTEN loss PI3K upregulation MYC overexpression CCNE1/2 amplification CDK2/ cyclin E CDK4/6i Resistance CDK2-cyclin E1 Degraders [1, 4, 5] [2,4] [2,5] [2] [3] [4] C. Elevated cyclin E1 and E2
expression correlates with poor patient survival and therapy resistance CCNE2 overexpression correlates with resistance to endocrine therapy in breast cancer2 High CCNE1 expression is associated with resistance to CDK4/6 inhibitor in breast
cancer3 1. TCGA (2011) Nature PMID: 21720365; 2. Milioli et al. (2020) Endocr Relat Cancer PMID: 32061162; 3. Freeman-Cook (2021) Cancer Cell PMID: 34520734 CCNE1 amplification correlates with poor survival in ovarian cancer
patients1 Patient Survival Months Survival CCNE1 diploid CCNE1 amplified
CDK2-Cyclin E Degrader for Treating CCNE1-amplified Solid Tumors and Breast
Cancer Resistant to CDK4/6 Inhibitors; IND Anticipated Q1 2027 Indication Solid tumors with CCNE1 amplification (CCNE1amp); HR+/HER2- breast cancer with CDK4/6i resistance; Patient Population Estimated in the US for 2024 by ACS
(cancer.org) and cbioportal analysis of TCGA database CCNE1amp solid cancer: >25,000 new cases/year Ovarian cancer (19,680 new cases, 19% CCNE1amp) Endometrial cancer (67,880 new cases, 10.8% CCNE1amp) TNBC (62,144 new cases, 10.7%
CCNE1amp) Esophagogastric cancer (49,260 new cases, 10.1% CCNE1amp) Non-small-cell lung cancer (187,664 new cases, 4% CCNE1amp) HR+HER2- metastatic breast cancer with CDK4/6i resistance: ~25,000 patients/year (310,720 new cases of breast
cancer, 73% are HR+, 20-30% with metastatic disease; 40-50% progression rate) Current SOC (US) Chemotherapy/ADCs Hormone therapy (ovarian, breast) Immunotherapy (breast, esophagogastric) Targeted therapy (e.g. CDK4/6i, HER2 mAb,
PARPi) Unmet Clinical Needs Chemo/ADCs/hormone/targeted therapy: drug resistance, side effects Immunotherapy: low response rate as monotherapy Clinical Position Solid tumors with CCNE1amp Breast cancer with CDK4/6i
resistance Biomarker CCNE1amp CDK4/6i resistant Proof-of-concept Study Phase 1a/1b with expansion cohorts in CCNE1amp ovarian, endometrial, TNBC, esophagogastric cancer as monotherapy; Phase 1a/1b with expansion cohorts in CDK4/6i
resistant HR+ breast cancer as monotherapy; B. Target product profile A. Deletion of CDK2/E1 re-sensitizes CDK4/6i-resistant cells to CDK4/6i1,2 C. Discovery of selective CDK2 - cyclin E dual degraders 1. Freeman-Cook (2021) Cancer Cell
PMID: 34520734; 2. Herrera-Abreu et al (2016) Cancer Res PMID: 27020857
CDK2-Cyclin E Degrader Demonstrates Greater In Vivo Anti-Cancer Efficacy Than
Phase 2/3 CDK2 Inhibitors in CDX and PDX Models All doses were well tolerated in animals, with no significant body weight loss observed during the studies B. CCNE1-amp MKN1 Gastric CDX C. CCNE1-amp HCC1599 TNBC CDX A. CCNE1-amp OVCAR3
Ovarian CDX F. Rb-deficient, CDK4/6i-resistant Breast PDX E. Chemo-resistant CCNE1-amp TNBC PDX D. CCNE1-amp HCC1569 Breast CDX
17 TYK2 - JAK1Dual-Degraderfor Inflammatory Diseases
A. TYK2/JAK - STAT signaling Tsokos GC.(2011) NEJM PMID: 22129255 McInnes
& Schett (2011) NEJM PMID: 22150039 B. SLE Mechanism C. RA Mechanism Platanias, LC. (2005) Nat Rev Immunol PMID:15864272 Significant Opportunity 125,000,000 psoriasis patients worldwide1 18,000,000 rheumatoid arthritis patients
worldwide2 ~204,000 lupus patients in the US in
Autoimmune Diseases,Focus on Systemic Lupus Erythematosus and Rheumatoid Arthritis
A. CG620953 is effective in a mouse model of systemic lupus erythematosus (SLE)
CG620953 Demonstrates Superior Efficacy in Preclinical Models of Lupus and Rheumatoid Arthritis (RA) B. CG620953 shows efficacy in a rat model of rheumatoid arthritis C. Targeted protein degradation in RA model Rat PBMC (1 month
dosing) Control CG620953 TYK2 -actin JAK1 Deucravacitinib (10 mpk, qd, po) Lupus model 10 mpk Control 30 mpk 60 mpk CG620953 (qd, po) Nose lesion score Dorsal skin lesion score Kidney histopathological Score Lupus model 10
mpk Control Vehicle 30 mpk 60 mpk Deucravacitinib (10 mpk, qd, po) CG620953 (qd, po) Kidney injury histopathology score CG620953, CG620953, CG620953,
Leveraging China Innovation Advantages to Advance Pipeline Products