Full Press Release Details
Corporate Presentation April 2025 Developing Anti-Fibrotic Therapeutics for
Chronic Organ Diseases
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 topline data from Gyre Pharmaceuticals' Phase 3 clinical trial evaluating F351 for the treatment of CHB-associated liver
fibrosis in the PRC, 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, 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 Gyre Therapeutics (Nasdaq: GYRE): At a glance 1ST to receive IPF1 treatment
approval (pirfenidone) in China (2011); Pioneering fibrosis treatment with a track record of success #1 IPF market share in China for 10 consecutive years2 (~50% market share, 90% + share in pirfenidone in 2024) ~ 600 dedicated global
employees; ~ 400 commercial team across China and the U.S. ~ 70 focused on R&D 150,000 + IPF patients treated with pirfenidone 3,000+ hospitals and pharmacies covered in China across 870+cities EBITDA positive since 20173, while
revenue grew at ~32% compounded annual growth rate (CAGR)3 during the same period 2024 Revenue: $105.8M 2 state-of-the-art, GMP compliant manufacturing facilities built for growth in China, currently running at 40% and 18% capacity 1. IPF
= Idiopathic Pulmonary Fibrosis. 2. Per IQVIA. 3. Financial data inclusive of pro forma data prior to GNI Group and Catalyst Biosciences business combination for comparison purposes only.
4 Investment Thesis: Pioneering anti-fibrotic solutions for unmet global health
needs Strong Pipeline Our lead asset, F351 (Hydronidone), has the potential to become a first-in-class therapy for CHB-related liver fibrosis, addressing a significant unmet medical need in China. Robust pipeline spanning various clinical
stages focused on treating organ diseases. Efficient R&D Strategy China-first validation strategy leveraging faster patient enrollment and cost efficiency, followed by expansion into the U.S. helps mitigate clinical and regulatory risks.
F351 is expected to initiate a Phase 2 trial in the U.S. for the treatment of MASH-associated liver fibrosis Proven Commercial Execution Maintaining market leadership since the commercialization of first-in-class pirfenidone in 2014, with
extensive and effective nationwide commercial coverage in China across more than 3,000 hospitals and pharmacies. Fully Integrated Platform Comprehensive in-house capabilities covering discovery, clinical development, regulatory affairs,
manufacturing, and commercialization. Two GMP-compliant manufacturing facilities are strategically located to support robust expansion.
5 Innovative fibrosis focused development pipeline with sentinel indications in
liver and lung CANDIDATE INDICATION PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 MARKETED RIGHTS TRIAL F351(Hydronidone) MASH-associated Liver Fibrosis Global Chronic Hepatitis B (CHB) Liver Fibrosis First F573 Acute Liver Failure /
Acute-on-Chronic Liver Failure F230 Pulmonary Arterial Hypertension (PAH) F528 Chronic Obstructive Pulmonary Disease (COPD) ETUARY(pirfenidone) Idiopathic Pulmonary Fibrosis (IPF) China First Radiation-induced lung injury (RILI) with
or without immune-related pneumonitis (CIP) Pneumoconiosis (PD) Diabetic Kidney Disease (DKD) Q2 2025: Ph2 IND Filing Q2 2025: Phase 3 Top-line Results 4Q 2025: Complete enrollment 4Q 2025: Start Phase 2/3 Trial (Adaptive Approach)
6 Our lead asset, Hydronidone, targets CHB fibrosis -- a high-need and untapped
market in China The market for CHB-associated liver fibrosis is significantly unmet. Current standard of treatment, e.g. entecavir, tenofovir, focuses on only reducing liver inflamation. Patients with F2 - F4 fibrosis are at a high risk of
progression to cirrhosis and HCC, major causes of liver-related mortality. Note: The Fourth National Serological Survey on HBV in China (2020) provided baseline HBV prevalence data. The 60-70M total HBV cases and F2-F4 fibrosis estimates are
derived using internal modeling based on this survey's fibrosis prevalence rates and awareness levels. Hydronidone, a structural analog of pirfenidone, reverses fibrosis by modulating TGF- / p38 / Smad7 signaling pathway - a key driver of
fibrosis progression. It received Breakthrough Therapy designation from PRC's NMPA in 2021, enabling expedited review. Initial Target Total HBV Infected Population in China 60 - 70 Million Chronic Hepatitis B (CHB) Diagnosed
Population 14.7 Million Progressed to Significant Fibrosis Population 5.5 Million Diagnosed Compensated F-2-F4 2.6 Million
7 Hydronidone demonstrates significant fibrosis regression with improved safety
profile in previous Phase 2 trial Trial Overview2 Description Patient Population Treatment Groups Testing Method Primary Endpoint Multicenter, double-blinded, placebo-controlled, Phase 2 trial evaluating Hydronidone in CHB-associated
liver fibrosis 168 patients with biopsy-confirmed fibrosis (F2-F4) 180mg, 270mg, 360mg Hydronidone + Entecavir vs. placebo Liver biopsy (histological fibrosis stage) 1 stage fibrosis improvement (Ishak score) at week 52 1. The reported %
of fibrosis improvement is based on the Intent-to-Treat (ITT) population. 2. Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial, Clinical Gastroenterology and Hepatology
(2022). A total of 7 patients (4.2%) experienced SAEs, comparable to placebo (4.6%). Most SAEs were mild/ moderate and resolved after stopping treatment.
8 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 The U.S. MASH
fibrosis market is 7.2x larger than CHB fibrosis. Clinical Rationale Hydronidone modulates TGF- / p38 / 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- , GLP-1s, and FGF21.
9 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- / p38 / Smad7 Hepatic Stellate Cells Anti-fibrotic via TGF- , p38 &
Smad7 Rationale for MASH expansion: Hydronidone targets the same core fibrotic biology - TGF- , p38 , 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 10 Pirfenidone [Structural Analog + OH] 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- TGF- + p38 + Smad7 Potency Metabolism Phase I (oxidation) Phase II (conjugation) Toxicity Hepatic
Safety Known liver risk Improved in Ph2 study Tolerability MASH Evidence Some benefit (PROMETEO, model)2 Stronger effect in a validated preclinical model Rationale 1. Phase II metabolism is associated with improved hepatic safety
due to faster detoxification.. 2. Gonz lez-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 p38 and upregulating Smad7, improving hepatic safety and supporting its expansion into metabolic liver diseases like MASH.
Hydronidone reduces fibrosis in a validated MASH mouse
model 11 Vehicle Hydronidone-15mpk Hydronidone-50mpk Endpoint Vehicle F351 (15 mpk) F351 (50 mpk) Fibrosis Severe Ballooning Present NASH Score High Hydronidone reduced fibrosis and ballooning in a
dose-dependent manner. Validates anti-fibrotic activity in a metabolic disease setting, supporting MASH expansion. Note: 100mpk not shown due to plateaued efficacy or potential toxicity. Validated in CCl + HFD-induced NASH model. Will
provide scientific package upon request.
12 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.
13 Positioning Hydronidone in the evolving MASH treatment
landscape ORAL INJECTABLE Hydronidone Rezdiffra VK2809 EFX Pegozafermin Tirzepatide Semaglutide Survodutide Indication CHB MASH MASH MASH MASH MASH MASH MASH Study Phase Phase 2 Approved Phase 2b Phase
2b Phase 2b Phase 2b Phase 2 Phase 2 MOA TGF- THR- THR- FGF21 FGF21 GIP/GLP-1 GLP-1 GLP-1/glucagon Population ITT ITT ITT ITT ITT ITT ITT Modified ITT ITT N
(Active/Placebo) 42/43 ~319/~309 44/41 43/43 63/61 81/45 219/219 80/80 77/77 Total ITT 168 966 181 126 181 192 659 320 295 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 54.8% ~26% 56.8% 49% 29% 27% 59.1% 43% 36% Placebo 25.6% ~10% 34.1% 19% 12% 7% 32.8% 33% 22% Placebo-Adjusted +29.2% +16% +22.7% +30% +17% +20% +26.3% +10% +14% Combination
Potential - 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. 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
Strategic moves to strengthen our pirfenidone franchise and prepare for potential
future hydronidone launch 14 ETUARY (pirfenidone)1 Nintedanib - Acquired in 2024 Avatrombopag - Acquired in 2024 2017 2024 $15.3m $105.8m 32% CAGR1 Expanding Our IPF Market: Gyre's ETUARY has dominated China's IPF market. Through
the strategic acquisition of a generic Nintedanib, we further strengthen our leadership by offering physicians a full spectrum of IPF treatments. Securing a Foothold in Liver Disease We acquired rights to a generic Avatrombopag as a strategic
entry point into the liver physician network-paving the way for the future launch of Hydronidone. ETUARY was approved in 2011 before the Reference Listed Drug (RLD) requirement. Without RLD, generic competitors can not conduct the required
bioequivalence (BE) studies. This creates a market exclusivity beyond patent protection. Financial data inclusive of proforma data prior to GNI Group and Catalyst Science merger for comparison purposes only. Note: 2017 sales number is
audited (China) and 2024 is audited (U.S. GAAP). See Note 2 above for further clarification. 2025 Sales Forecast: $118m-$128m
15 Transitioning into a fully integrated global biopharma company Beijing
Office Shanghai Office Shunyi Manufacturing Facility CangZhou Manufacturing Facility Dual Global Headquarters San Diego, CA Beijing, China Integrated Manufacturing Infrastructure Shunyi Facility (Beijing): State-of-the-art R&D and
manufacturing center - adding annual capacity of 700 million capsules. Cangzhou Facility: Robust API production center with 50 tons annual capacity. Rigorous Quality Systems Integrated Quality Management System to ensure consistent product
identity, safety, and efficacy. San Diego Headquarters
Expected milestones for Hydronidone 16 1H 2025 2H 2025 1H 2026 Gyre plans to
advance additional pipeline compounds including pirfenidone, F573, F528, and F230in a variety of fibrotic and inflammatory diseases Submission of New Drug Approval 2Q 2025 NMPA Approval 2026 Initiate Phase 2 in MASH-Associated liver
Fibrosis FDA Meeting Q2/3 2025 2H 2026
Market leader in IPF with ETUARY in China. China-first, U.S.-second development
strategy. De-risked approach with efficient resource allocation. Integrated platform: R&D, regulatory, manufacturing, commercial. 17 Gyre: Building on proven success with a measured, de-risked approach to drive sustainable
growth Scientific Innovation Demonstrated fibrosis reversal in CHB Phase 2 trial, Phase 3 read-out expected in 2Q25. Breakthrough Therapy designation in China. Distinct anti-fibrotic MoA; complementary to metabolic agents. U.S. Phase 2 in
MASH expected in 2025. Proven Execution Strategic Growth Hydronidone currently planned for dual-market success (CHB + MASH). Positioned to become a category leader in fibrosis care. Significant unmet global markets with multi-billion
potential. Backed by long-term parent GNI Group .