Exhibit 99.1
A Fully-Integrated Biopharmaceutical Company Focused on Fibrosis, Inflammatory Diseases and Cancer
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 Fibrosis
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-β and p38γ 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-β 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-β 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 20183 https://www.psoriasis.org/psoriasis-statistics/ https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis https://www.niams.nih.gov/health-topics/lupus/basics/symptoms-causes Dual Targeting of TYK2 and JAK1 for 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 β-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
Gyre’s China Innovation and Validation Engine Provides Ability to Leverage China’s Unique Ecosystem Pillars ARC Group Insights – July 21, 2025 Comparison vs. Boehringer Ingelheim nerandomilast phase 3 study Drug Discovery Capabilities Streamlined Clinical Enrollment Cooperative Regulatory Environment Rapid enrollment (weeks vs. months)1 Dense urban clinical sites (Beijing, Shanghai, Guangzhou) Treatment-naïve patient base1 Lower operational costs Affordable STEM talent Early-stage development up to 55% faster1 Similar IND approval speed as U.S. FDA Priority review and breakthrough designation Harmonization with int’l standards NMPA reforms Established network of healthcare providers ETUARY™ Phase 3 IPF study enrolled patients 3x faster than most recent Phase 3 IPF study in USA2. Creation of >1,000 functional degraders each year since inception DAC creation to NHP testing in as few as 3 months F351 Breakthrough designation F351 Priority Review status CLINICAL DISCOVERY REGULATORY China Ecosystem Opportunities Examples of Gyre Success China Advantage: Speedy Timelines International Standards Cost-effective Operations
Degraders for Cancer andCancer-induced Bone Pain- TRK degrader (CG001419)- GSPT1 degrader (CG009301)
Targeting TRK for Pain and Cancer Cocco, Scaltriti & Drilon (2018) Nat Rev Clin Oncol PMID: 30333516 B. Activation of TRK in multiple solid tumors A. TRK signaling pathways
Clinical Development of CG001419 for Cancer Future Data Points Data from first 22 patients demonstrated no observed DLTs, treatment-related SAEs or grade ≥3 treatment related AEs. Enrollment in Phase 1b (dose expansion portions) began Q1 2026. RDE Phase 1a Dose Escalation 1b Dose Expansion Phase 2 Basket Trial Dose level 1, n =3~6 Dose level 2, n=3~6 Dose level 3, n=3~6 Dose level 4, n=3~6 “3+3” Group 1: NTRK fusion w/o prior TRK-TKI Group 2: NTRK fusion failed prior TRK-TKI Group 3: NTRK point mutations Group 4: NTRK gene amplification or overexpression Dose #1, n=6~15 R2PD Dose #2, n=6~15 Dose level 5, n=3~6 Dose level 6, n=3~6 Dose level 7, n=3~6
Summary of CG001419 for Cancer 2 1 3 Clinical Strategy Clinical Development Plan Positioning and Differentiation Exploratory study in cancer patients with NTRK amplification, overexpression and point mutations A rational, step-wise, biomarker-driven Phase 1/2 study design with expansion cohorts to provide early efficacy readout and assess the safety, PK and PK/PD relationships in selected tumors If successful, expected accelerated regulatory pathway toward early approval, including breakthrough designation Early incorporation of biomarker strategy supports development of precision treatment and associated companion diagnostic (CDx) First-in-Class, selective, oral TRK degrader for the treatment of adult cancer patients with NTRK gene abnormalities Potential use in cancer patients with NTRK gene fusion who acquire resistance to prior TRK kinase inhibitors via NTRK mutations
NGF And TRK Are Key Mediators of Acute and Chronic Pain A. Nerve growth factor (NGF) stimulates the TrkA signaling pathway to transmit pain to the central nervous system TrkA Dorsal root ganglion (DRG) NGF Injury / Inflammation Brain NGF-TRKA complex C. Blocking NGF reduces cancer bone pain B. TRKA mutations cause congenital insensitivity to pain and anhidrosis (CIPA) Mutations identified in: 22 genes Mutation in TRKA: 20 patients Mutation in NGF: 2 patients Mutation in Nav1.7: 22 patients Other 19 genes: 34 patients Indo et al (1996) Nat Genet. PMID: 8696348 Lischka et al (2023) Brain PMID: 37769650 Sequencing of a cohort 78 CIPA patients Fallon et al. (2023) Oncologists PMID: 37343145
Summary of Phase 1 PD, PK and Safety Study of CG001419 CG001419-101 (NCT06636500): a SAD/MAD/FE study in healthy subjects in Australia The surrogate PD assay demonstrated DC50 and DC90 values of 2.4 nM and 18.2 nM, respectively Single and multiple oral doses of CG001419 up to the highest dosing levels were safe and well tolerated by the healthy subjects In the SAD/FE of the study, 72.2% had a TEAE and in the MAD 83.9% had a TEAE Most TEAEs were considered mild or moderate at their maximum severity in both parts of the study. No Grade 4 (potentially life-threatening) TEAEs were reported The most frequently reported TEAEs by SOC were general disorders and administration site conditions. Since the drug was administered orally, these were likely due to blood collection procedures Following a single oral dose, the exposure to CG001419 increased in a dose-proportional manner The food-effect cohort demonstrated a higher systemic exposure under the fed condition For the MAD cohorts after multiple daily dosing for 7 days, exposure to CG001419, metabolite M2 and M8 increased in a less than dose-proportional manner Single Ascending Dose (SAD) PK Dose level 1 (n = 6) Dose level 3 (n = 12) Dose level 5 (n = 6) Dose level 2 (n = 5) Dose level 4 (n = 6) Dose level 6 (n = 6) Nominal Time (hours) Concentration (ng / mL) DC50=2.4 nM DC90=18.2 nM Surrogate PD assay Multiple Ascending Dose (MAD) PK (Day 7) Dose level 5 (n = 6) Dose level 3 (n = 6) Dose level 6 (n = 6) Dose level 4 (n = 6) Nominal Time (hours) Concentration (ng / mL) DC90
CG001419: Differentiated as a Potential First in Class Non-Opioid Medicine for the Treatment of Pain Opioids NSAIDs Cebranopadol Journavx (Suzetrigine,VX-548) VX-993 LTG-001 STC-004 CG001419 Safety Concerns Risk to develop dependency GI issues, headache, dizziness Nausea - - - - - Effective Moderate Moderate Moderate Did not meet acute pain primary endpoint TBD TBD Preclinical studies MOA Neuron hyperpolarization COX inhibitor Dual-NMR (NOP and opiate receptor) agonist First-in-class Nav1.8 inhibitor First-in-class Nav1.8 inhibitor Fast-follower Nav1.8 inhibitor Fast-follower Nav 1.8 inhibitor Fast-follower TRK degrader First-in-class Non-addictive Rapid development (< 5 – 14 days) TBD Phase Approved Approved Phase 3 Trials Complete Approved Discontinued as monotherapy for acute pain Phase 1 Complete Phase 1 Complete Phase 1 Complete
Cancer-induced Bone Pain Market Opportunity Current pharmacological therapies to treat CIBP are inadequate, with 70% treated with opioids reporting continued bone pain1 Tanezumab, an NGF antibody, showed reduction in pain in phase III trials of cancer patients with bone pain2 Opioids – Marginally effective at relieving CIBP and come with significant side-effects (nausea, vomiting, constipation) especially for advanced or palliative stage cancer patients where quality of life is paramount 1. https://pubmed.ncbi.nlm.nih.gov/30627511 2. https://pubmed.ncbi.nlm.nih.gov/37343145 3. https://pubmed.ncbi.nlm.nih.gov/22570568 4. https://pubmed.ncbi.nlm.nih.gov/26229504 4. https://pubmed.ncbi.nlm.nih.gov/23344095 6. https://pubmed.ncbi.nlm.nih.gov/25919474 7. https://pubmed.ncbi.nlm.nih.gov/37343145 8. Estimates based on treatment pricing of $10 / day
2 1 3 Clinical Strategy Clinical Development Plan Positioning and Differentiation Rational, mechanism-based selection of indications and target populations Planned Phase 2 study in cancer-induced bone pain applications Objectives: 1) magnitude and time course of CG001419 analgesia relative to placebo 2) safety of CG001419 compared to placebo 3) PK characteristics of CG001419 Phase 1a trial in Australia to assess PK and safety completed Q4 2025 Phase 2 POC trial in patients with cancer-induced bone pain or other metastatic cancer pain syndromes First-in-class TRK degrader as an analgesic for acute and chronic pain Potential for differentiation in efficacy and safety from NSAIDs, opioids, and NAV1.8 inhibitors via novel mechanism of action Summary of CG001419 for Pain
Targeting GSPT1 for AML and MYC+ Cancers GSPT1 controls protein translation termination and plays important function for leukemia stem cells and tumor cells with MYC overproduction. GSPT1 lacks an active site and is often considered “undruggable”. Cullgen has developed a potent and selective GSPT1 degrader, CG009301. Preclinical studies have validated the selectivity, potency and safety of CG009301. US Patient Population 1 2024 by American Cancer Society estimates 2 The Cancer Genome Atlas (TCGA) estimates 3 Schaub et al (2018) Cell Syst PMID: 29596783 4 Volpe et al. (2022) Clin Lymphoa Myelom Leuk, PMID: 34544674 AML1 MDS1 ALL1 MYC-amplified solid tumors2,3 ~20,800 new cases ~10,000 new cases ~6,500 new cases 28% 11,220 mortality 30-40% MDS progress to AML4 1,330 mortality Worldwide
Dose Escalation Stage Dose Expansion Stage* Dose level 1, n =1 Dose level 2, n=1 Dose level 3, n=3~6 Dose level 6, n=6~12 Dose level 7, n=6~12 BOIN Design Dose #1, n=9~18 Dose #2, n=9~18 Dose level 4, n=3~6 Dose level 5, n=3~6 Accelerated Titration Phase 2* R/R AML or HR-MDS or R/R ALL RDE Dose level 8, n=3~6 Dose level 9, n=3~6 Dose level 10, n=3~6 Dose escalation stage currently underway Data from first 8 patients demonstrated no observed DLTs Anticipate enrollment of approximately 30 – 45 patients Clinical Development of CG009301 in Patients with Recurrent or Refractory Hematologic Malignancies * Subject to regulatory alignment RP2D
2 1 3 Clinical Strategy Clinical Development Plan Positioning and Differentiation Cullgen initiated a Phase 1 clinical trial in subjects with refractory hematologic malignancies in April 2025 in China. The expansion cohorts will focus on R/R AML, HR-MDS and ALL patients with hopes of identifying the optimal cohort for subsequent Phase 2 testing. The Phase 1a/1b data is expected to be submitted as the basis for an IND application to conduct the Phase 2 studies in the chosen disease population Relapsed / refractory AML, HR-MDS, and ALL patients Potential to also treat relapsed / refractory MYC-driven solid tumors Pre-clinical leukemia models indicate strong anti-tumor activity Summary of CG009301 for Cancer
34 Degrader-Antibody Conjugates (DACs)
Degrader-Antibody Conjugates (DACs) Are the Next-Generation of ADCs DAC (Degrader antibody conjugate) TPD (Targeted protein degradation) E3 ligase E3 ligase ADC (Antibody drug conjugate) Modality ADCs TPD DAC Mechanism of Delivery Intravenous Oral or IV Intravenous Payload Indiscriminate Tumor target selective Target selective Efficacy Requires potent payload Catalytic & potent Catalytic & potent Tumor Selective Delivery Tumor cell selective Depends on E3 Tumor cell selective Ability to Reduce Off Target Toxicity No Depends on E3 Yes Need for oral bio-availability or cell permeability optimization No Yes No
DAC Mechanism of Action Overview The catalytic mechanism of action of TPDs ensures small quantity of degrader delivered by the antibody to achieve sufficient efficacy. HIGH POTENCY Extended half-life, reduced systemic clearance, improved solubility, and bypassing the need for oral bio-availability or cell permeability optimization. IMPROVED pk Reduced toxicity through dual target selectivity at the cell surface (antibody-tumor associated antigen) and intracellularly (degrader-target protein). IMPROVED SAFETY
Epigenetic Factor DAC Demonstrates Potent and TAA-dependent Target Degradation and Cell Killing Cell Line TAA Positive Cell Line Compounds (nM） DMSO Degrader DAC DMSO Linker-degrader DMSO 0.01 0.1 1 10 100 0.01 0.1 1 10 100 0.01 0.1 1 10 100 Lane 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Cell Line TAA Negative Cell Line Compounds (nM） DMSO Degrader DAC DMSO Linker- degrader mAb DMSO 0.01 0.1 1 10 100 0.01 0.1 1 10 100 0.01 0.1 1 10 100 10 100 Lane 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 p300 CBP Actin p300 CBP GAPDH A. Cullgen epigenetic factor DAC induces potent protein target degradation in a TAA-dependent manner in vitro B. Cullgen epigenetic factor DAC kills cancer cells in a TAA-dependent manner Linker-degrader (IC50: 24.25 nM) Naked antibody (IC50: > 1uM) Degrader (IC50: 0.08nM) DAC (IC50: 0.08 nM) TAA Positive Cells Linker-degrader (IC50: 103 nM) Naked antibody (IC50: > 1uM) Degrader (IC50: 0.61 nM) DAC (IC50: 138 nM) TAA Negative Cells Protein 1 Protein 2 Protein 1 Protein 2
Degrader-Antibody Conjugates: Durable Tumor Regression, Superior to Dxd-ADC, and Overcoming Resistance in CDX and PDX Animal Models A. DACs exhibit durable tumor growth inhibition in various solid tumor models B. DACs are more effective than Dxd-based ADCs C. DACs are effective in a CRPC PDX model resistant to enzalutamide
Degrader 2 Gyre Has Established a Robust DAC Platform DACs represent the next generation of ADC therapies Cullgen has developed >7,000 active degraders targeting >20 distinct proteins, serving as a valuable resource for payload selection We have successfully generated multiple DACs and demonstrated their selectivity, efficacy and safety Conjugating a diverse array of degraders to different antibodies offers the opportunity to selectively target different cancer types Degraders May be Combined with Different mAbs to Create Novel DACs Targeting Specific Cancers Degraders TAAs (Tumor-assisted Antigens) Clinical Indications Developing therapies for: Degrader 1 mAb 1 mAb 2 mAb 3 mAb 4 mAb 6 mAb 5 Degrader 1 interactions Degrader 2 interactions + other cancers Breast Cancer UC Prostate cancer NSCLC SCLC Gastric Cancer HNSCC NPC AML
Ying Luo, Ph.D. Chief Executive Officer Thomas Eastling Chief Financial Officer Weiguo Ye Chief Operating Officer Yue Xiong, Ph.D. Chief Scientific Officer Mark Marino, M.D. Senior Vice President –Clinical Development Michael Plewe, Ph.D. Senior Vice President - Medicinal Chemistry Leslie Robinson, Ph.D., J.D. Vice President - Intellectual Property and Licensing Liang Zhao VP Corporate Controller U.S. Management Team with Cross-Culture Operational Experience Jialiang Wang, Ph.D. Executive Vice President, General Manager Joshua Bergmann, J.D. General Counsel and Corporate Secretary Ruoyu Chen Chief Information Officer Seth Goldblum, MBA Senior Vice President - Corporate Development Jing Liu, Ph.D. Senior Vice President – Platform Chemistry
Key Value Drivers Robust and balanced therapeutic pipeline including assets from discovery to marketed products, with established manufacturing and commercialization operations 1 Utilization of highly efficient and cost-effective drug discovery and innovation capabilities in China to advance risk-mitigated products to the United States 2 Strong foundation in protein degrader development provides distinct advantage for the development of DACs as next generation ADC therapeutics 3 Accomplished management team in the United States and China with extensive international business operations experience 4
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