Developing Anti-Fibrotic Therapeutics for Chronic Organ Diseases Corporate Presentation April 2025 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 Gyre T ...

Company Overview - Gyre Therapeutics is a biopharmaceutical company focused on advancing fibrosis-first therapies across various organ systems affected by chronic diseases [1][6] - The company is headquartered in San Diego, CA, and is primarily engaged in the development and commercialization of Hydronidone for liver fibrosis, including metabolic dysfunction-associated steatohepatitis (MASH) [6] Clinical Development - Gyre has successfully dosed the first volunteer in a Phase 1 clinical trial for F230, a novel endothelin A receptor antagonist aimed at treating pulmonary arterial hypertension (PAH) [1][4] - The Phase 1 trial is designed to evaluate the safety, tolerability, and pharmacokinetics of F230 in healthy volunteers [4] - F230 is a fully synthetic small molecule that selectively blocks the ETA receptor, intended to reduce pulmonary vascular remodeling and lower pulmonary pressure, which are critical factors in PAH progression [3] Market Potential - Gyre's entry into the PAH field is significant due to the condition's rarity, progressive nature, and high mortality rate, with limited treatment options available [2] - The PAH market in China was valued at $370 million in 2023 and is projected to grow to $480 million by 2031, highlighting the commercial potential for Gyre's F230 [2] Pipeline and Future Plans - F230 joins Gyre's pipeline alongside its lead candidate Hydronidone (F351), which has met the primary endpoint in a pivotal Phase 3 trial for chronic hepatitis B (CHB)-induced liver fibrosis [5] - A New Drug Application (NDA) submission for F351 to China's National Medical Products Administration (NMPA) is planned for the third quarter of 2025 [5] - Gyre is also planning a pre-IND meeting with the U.S. Food and Drug Administration for an expected Phase 2 trial in MASH fibrosis [5]

Core Viewpoint - Gyre Therapeutics has successfully completed a public offering of 2,555,555 shares at a price of $9.00 per share, raising approximately $23.0 million in gross proceeds to advance its clinical trials and operations [1][3]. Group 1: Offering Details - The public offering included the full exercise of an option by underwriters to purchase an additional 333,333 shares [1]. - Jefferies acted as the lead book-running manager, while H.C. Wainwright & Co. served as co-manager for the offering [2]. Group 2: Use of Proceeds - The net proceeds from the offering will be utilized to advance Gyre's Phase 2 clinical trial of F351 for MASH-associated liver fibrosis, along with funding for research and development, manufacturing scale-up, and general corporate purposes [3]. Group 3: Company Overview - Gyre Therapeutics is focused on developing and commercializing therapies for liver fibrosis, particularly targeting MASH in the U.S. market [6]. - The company leverages its experience in mechanistic studies and clinical trials related to liver fibrosis [6].

Core Viewpoint - Gyre Therapeutics has announced a public offering of 2,222,222 shares at a price of $9.00 per share, aiming to raise approximately $20 million to support its clinical trials and operational needs [1][3]. Group 1: Offering Details - The public offering consists of 2,222,222 shares priced at $9.00 each, with an option for underwriters to purchase an additional 333,333 shares [1]. - The gross proceeds from the offering are expected to be around $20 million before deducting underwriting discounts and commissions [1]. - The offering is anticipated to close on or about May 27, 2025, pending customary closing conditions [1]. Group 2: Use of Proceeds - Gyre plans to utilize the net proceeds from the offering, along with existing cash and cash flows, to advance its Phase 2 clinical trial of F351 for liver fibrosis associated with metabolic dysfunction [3]. - The funds will also be allocated for research and development, manufacturing scale-up, working capital, and general corporate purposes [3]. Group 3: Company Background - Gyre Therapeutics is a biotechnology company based in San Diego, focusing on organ fibrosis, particularly liver fibrosis related to metabolic dysfunction [6]. - The company is advancing a pipeline in China through its indirect controlling interest in Gyre Pharmaceuticals, which includes various therapeutic developments [6].

Core Viewpoint - Gyre Therapeutics has initiated an underwritten public offering of its common stock to fund its clinical trials and operational needs [1][2]. Group 1: Offering Details - Gyre is granting underwriters a 30-day option to purchase additional shares at the public offering price, subject to market conditions [1]. - The offering is made under a shelf registration statement effective since November 22, 2024, and will be conducted via a prospectus [4]. Group 2: Use of Proceeds - The net proceeds from the offering will be used to advance Gyre's Phase 2 clinical trial of F351 for MASH-associated liver fibrosis, along with funding for research, development, manufacturing, and general corporate purposes [2]. Group 3: Management of the Offering - Jefferies is the lead book-running manager for the offering, with H.C. Wainwright & Co. serving as co-manager [3]. Group 4: Company Overview - Gyre Therapeutics is focused on developing and commercializing treatments for liver fibrosis, including MASH, and has a pipeline that includes various therapeutic programs in the U.S. and China [6].

Core Insights - Gyre Therapeutics announced that its lead compound, Hydronidone (F351), successfully met the primary endpoint in a pivotal Phase 3 trial for treating liver fibrosis in patients with chronic hepatitis B in China [1][2][3] Trial Details - The Phase 3 trial was a 52-week, multicenter, double-blind, placebo-controlled study involving 248 patients with CHB fibrosis across 39 hospitals in China [2][12] - Patients were randomized 1:1 to receive either Hydronidone (270 mg/day) or placebo, alongside entecavir antiviral therapy [2][12] - The trial achieved a statistically significant proportion of patients showing a ≥1-stage regression in liver fibrosis with Hydronidone compared to placebo (52.85% vs. 29.84%, P=0.0002) [6][7] Efficacy and Safety Results - Hydronidone demonstrated a statistically significant regression in liver fibrosis and improvement in liver inflammation compared to placebo [5][6] - Key secondary endpoint results showed a ≥1-grade improvement in inflammation (49.57% for Hydronidone vs. 34.82% for placebo, P=0.0246) [6] - The safety profile of Hydronidone was favorable, with serious adverse events occurring in 4.88% of patients compared to 6.45% in the placebo group, and no discontinuations due to adverse events [7][9] Future Plans - Gyre plans to submit a New Drug Application (NDA) to China's NMPA in Q3 2025 for accelerated approval of Hydronidone [7][11] - A Phase 2 trial in the U.S. for MASH-associated liver fibrosis is expected to begin in the second half of 2025 [7][11] Market Opportunity - Approximately 75 million people in China are chronically infected with hepatitis B, with an estimated 2.6 million diagnosed with compensated F2-F4 CHB fibrosis, representing a significant addressable market for Hydronidone [13][14] - Currently, there are no approved anti-fibrotic therapies for CHB fibrosis in China, highlighting the urgent medical need that Hydronidone aims to address [13][14] About Hydronidone - Hydronidone is a structural analogue of Pirfenidone, exhibiting enhanced potency in inhibiting key drivers of liver fibrosis [15][16] - The compound has shown robust anti-fibrotic activity in multiple preclinical models and is positioned to transform the treatment landscape for liver fibrosis [16] Company Overview - Gyre Therapeutics is a biopharmaceutical company focused on developing and commercializing Hydronidone for liver fibrosis, including MASH in the U.S. [18] - The company is advancing a broad pipeline through its indirect controlling interest in Gyre Pharmaceuticals, including therapeutic expansions and development programs [18]

Commercialization and Product Development - Gyre Pharmaceuticals successfully advanced pirfenidone to commercialization in the PRC for the treatment of idiopathic pulmonary fibrosis (IPF) and has acquired commercial rights to Nintedanib, enhancing its position in the pulmonary fibrosis market[116] - Nintedanib is expected to be commercialized in the PRC in Q2 2025, aimed at offsetting declines in ETUARY sales due to increased competition and economic fluctuations[116] - Pirfenidone is undergoing a Phase 3 trial in the PRC for pneumoconiosis and has received approval for a new indication for radiation-induced lung injury[118] - F351, a lead development candidate, has shown statistically significant improvement in liver fibrosis in a Phase 2 trial, with a confirmatory Phase 3 trial ongoing[120] - The Phase 3 trial of Hydronidone in CHB-associated liver fibrosis is on track to report topline results in Q2 2025[120] - The commercialization of avatrombopag in the PRC was initiated in March 2025, targeting thrombocytopenia in chronic liver disease[123] - Gyre Pharmaceuticals is preparing to launch a clinical trial for F230, a selective endothelin receptor agonist for pulmonary arterial hypertension[122] - The company is also evaluating F528, a novel anti-inflammation agent, in preclinical studies for chronic obstructive pulmonary disease[122] Financial Performance - For the three months ended March 31, 2025, the company reported revenues of $22.1 million, a decrease of $5.1 million or 19% compared to $27.2 million in the same period of 2024[150] - The net income for the three months ended March 31, 2025, was $3.7 million, down 62% from $9.9 million in the same period of 2024[137] - Research and development expenses increased by $0.9 million, or 42%, for the three months ended March 31, 2025, totaling $3.1 million compared to $2.2 million in 2024[155] - Selling and marketing expenses decreased by $1.7 million, or 14%, for the three months ended March 31, 2025, totaling $10.8 million compared to $12.5 million in 2024[154] - The cost of revenues for the three months ended March 31, 2025, was $0.9 million, a decrease of 9% from $1.0 million in the same period of 2024[153] - The provision for income taxes was $0.9 million for the three months ended March 31, 2025, down from $2.5 million in 2024, primarily due to lower profits[159] Cash Flow and Financial Position - The company had cash and cash equivalents of $15.0 million as of March 31, 2025, an increase from $11.8 million as of December 31, 2024[137] - The accumulated deficit as of March 31, 2025, was $70.8 million, a slight improvement from $73.5 million as of December 31, 2024[137] - Cash used in operating activities was $0.1 million, reflecting a net income of $3.7 million, offset by non-cash items totaling $0.5 million[166] - Cash provided by investing activities for the same period was $2.0 million, primarily from $11.2 million cash acquired from maturing certificates of deposit, offset by $8.4 million in purchases of certificates of deposit[168] - Cash provided by financing activities for the three months ended March 31, 2025, was $1.3 million, driven by $0.9 million from stock options exercise and $0.5 million from common stock issuance[170] - As of March 31, 2025, the aggregate amounts of restricted capital and statutory reserves not available for distribution were $64.3 million[171] Commitments and Obligations - The company has committed to allocate $32.7 million toward future research and development activities as of March 31, 2025[175] - The company has fixed lease payment obligations of $1.8 million as of March 31, 2025, with $0.8 million payable within 12 months[173] - The company has commitments related to the purchase of property and equipment totaling $4.8 million as of March 31, 2025[176] - The company expects to pay a total of $1.0 million to New Jiyuan for the transfer of minocycline hydrochloride foam, with $0.7 million paid as of March 31, 2025[174] Reporting Status - The company remains a smaller reporting company but became an "accelerated filer" as of December 31, 2024, requiring compliance with additional reporting requirements[180]

Core Viewpoint - Gyre Therapeutics reported a net income of $3.7 million for Q1 2025 and reaffirmed its full-year revenue guidance of $118 to $128 million, indicating a strategic focus on expanding its market presence and product portfolio in the organ fibrosis treatment space [1][12]. Financial Performance - Revenues for Q1 2025 were $22.1 million, down from $27.2 million in Q1 2024, primarily due to a $5.2 million decline in ETUARY sales, which was anticipated following a one-time marketing campaign in early 2024 [12][18]. - The company reported a decrease in income from operations to $2.3 million from $8.1 million year-over-year, attributed to lower revenues [18]. - Non-GAAP adjusted net income for Q1 2025 was $2.9 million, down from $8.2 million in the same period last year, reflecting the decline in revenue and a slight increase in operating expenses [18][28]. Business Highlights - The launch of avatrombopag in March 2025 is expected to enhance Gyre's presence in hepatology and hematology, targeting thrombocytopenia in adults with chronic liver disease [5][6]. - ETUARY (pirfenidone) generated $21.7 million in sales during Q1 2025, maintaining its position as the market leader for idiopathic pulmonary fibrosis (IPF) in China, despite a year-over-year sales decline [3][12]. - Nintedanib is on track for commercial launch in May 2025, aimed at treating multiple forms of fibrosing interstitial lung disease, which is anticipated to support revenue growth in the second half of 2025 [4][12]. Pipeline Development - Gyre received NMPA approval to initiate a clinical trial of pirfenidone for radiation-induced lung injury (RILI), marking its entry into oncology supportive care, with plans for an adaptive Phase 2/3 trial in the second half of 2025 [6][7]. - The company is also advancing F573, a caspase inhibitor for acute liver failure, with a Phase 2 clinical trial completion expected by the end of 2026 [8][12]. - F230, a selective endothelin receptor agonist for pulmonary arterial hypertension, is set to begin a Phase 1 trial in Q2 2025 [9]. Corporate Updates - In March 2025, Gyre appointed Ping Zhang as Executive Chairman of the Board of Directors, indicating a strategic leadership change [11]. Cash Position - As of March 31, 2025, Gyre held $51.3 million in cash, cash equivalents, and deposits, which the company believes will be sufficient to fund its operating and capital requirements for the next 12 months [12][18].

Financial Performance - Net income for Q1 2025 was $3.7 million, down from $9.9 million in Q1 2024, primarily due to lower revenue and unfavorable changes in fair value of warrant liabilities [19]. - Q1 2025 revenue was $22.1 million, a decrease of $5.1 million compared to $27.2 million in Q1 2024, attributed to a decline in ETUARY® sales and weaker economic conditions in China [14]. - Revenues for Q1 2025 were $22,058 million, a decrease of 18.5% compared to $27,172 million in Q1 2024 [27]. - Net income for Q1 2025 was $3,734 million, down 62.5% from $9,935 million in Q1 2024 [27]. - The company reported a non-GAAP adjusted net income of $2,887 million for Q1 2025, compared to $8,204 million in Q1 2024, reflecting a decline of 64.8% [32]. - Basic net income per share attributable to common stockholders was $0.03 for Q1 2025, down from $0.09 in Q1 2024 [27]. Sales and Revenue Guidance - ETUARY® (pirfenidone) generated $21.7 million in sales during Q1 2025, maintaining its position as the market leader for idiopathic pulmonary fibrosis (IPF) in China [4]. - Gyre Therapeutics reaffirmed its full-year 2025 revenue guidance of $118 to $128 million, compared to $105.8 million in 2024 [14]. Research and Development - The company completed data collection for the pivotal Phase 3 trial of Hydronidone in Chronic Hepatitis B-associated liver fibrosis, with topline results expected in Q2 2025 [5]. - Research and development expenses increased to $3.1 million in Q1 2025, up from $2.2 million in Q1 2024, driven by clinical research costs [16]. - Gyre received NMPA approval to initiate a clinical trial of pirfenidone for radiation-induced lung injury, marking its entry into oncology supportive care [8]. Commercialization Efforts - Commercialization of avatrombopag was initiated in March 2025, targeting thrombocytopenia in adults with chronic liver disease [7]. - Nintedanib is on track for commercialization in May 2025, expanding treatment options for pulmonary fibrosis [6]. Financial Position - As of March 31, 2025, Gyre held $51.3 million in cash and cash equivalents, sufficient to fund operations for the next 12 months [13]. - Cash and cash equivalents increased to $15,045 million as of March 31, 2025, up from $11,813 million at the end of 2024 [30]. - Total assets rose to $129,790 million as of March 31, 2025, compared to $125,406 million at the end of 2024 [30]. - Total liabilities decreased to $25,488 million as of March 31, 2025, down from $27,004 million at the end of 2024 [30]. - The company’s accumulated deficit improved to $(70,755) million as of March 31, 2025, from $(73,453) million at the end of 2024 [30]. Operating Expenses - Operating expenses totaled $19,785 million in Q1 2025, slightly up from $19,101 million in Q1 2024, with significant increases in research and development expenses from $2,182 million to $3,095 million [27]. - The weighted average shares used in calculating diluted net income per share were 101,970,672 for Q1 2025, compared to 102,594,197 for Q1 2024 [27].

Core Viewpoint - Gyre Therapeutics has received approval from the National Medical Products Administration (NMPA) in China for a clinical trial application to evaluate pirfenidone for treating radiation-induced lung injury (RILI) and immune-related pneumonitis (CIP) in cancer patients [1][2]. Company Overview - Gyre Therapeutics is a biotechnology company focused on organ fibrosis, with a commercial-stage product, pirfenidone, which is currently approved for idiopathic pulmonary fibrosis (IPF) [1][7]. - The company is headquartered in San Diego, CA, and is advancing a broad pipeline in China through its indirect controlling interest in Gyre Pharmaceuticals [8]. Clinical Trial Details - The approved trial will utilize an adaptive Phase 2/3 design to explore dosing and confirm efficacy for pirfenidone in the new indication [2]. - Gyre plans to initiate the trial in the second half of 2025 at leading academic and oncology centers across China [6]. Medical Context - RILI affects 5%–25% of lung cancer patients undergoing radiation therapy, which can limit treatment efficacy [3]. - CIP occurs in 13%–19% of patients treated with immune checkpoint inhibitors, contributing to a significant percentage of immune-related adverse event deaths [4]. - Currently, there are no targeted therapies for lung injuries caused by radiation or immunotherapy, with corticosteroids being the standard treatment despite their long-term side effects [5]. Drug Mechanism - Pirfenidone is an orally administered small molecule that inhibits TGF-β signaling and fibroblast proliferation, showing clinical benefits in slowing lung function decline in IPF [7].