Gyre Therapeutics details pipeline and CG923308 data

Rhea-AI Filing Summary

Gyre Therapeutics, Inc. furnished a scientific presentation it will deliver at a conference in Shanghai, outlining its strategy as a fully integrated biopharmaceutical company focused on fibrosis, inflammatory diseases and cancer, including the recently announced acquisition of Cullgen.

The presentation highlights a broad pipeline from discovery to marketed products and a global footprint with headquarters in San Diego and major discovery, development, manufacturing and commercial operations in China. Gyre reports about 740 employees worldwide across R&D, manufacturing, sales and marketing, and G&A functions.

A key focus is CG923308, a CDK2/cyclin E degrader for CCNE1-amplified solid tumors and HR+/HER2- breast cancer resistant to CDK4/6 inhibitors. Preclinical data show potent, selective protein degradation, oral bioavailability in multiple species, strong in vitro and in vivo anti-cancer activity versus Phase 2/3 CDK2 inhibitors, and tolerability in animal models. Cullgen anticipates submitting an Investigational New Drug application for CG923308 in the first quarter of 2027. The presentation is furnished as Exhibit 99.1 under Item 7.01 and is not deemed filed under the Exchange Act.

8-K Event Classification

2 items: 7.01, 9.01

2 items

Item 7.01 Regulation FD Disclosure Disclosure

Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.

Item 9.01 Financial Statements and Exhibits Exhibits

Financial statements, pro forma financial information, or exhibit attachments filed with this report.

Key Figures

Workforce size: 740 employees R&D staff: 170 employees Manufacturing staff: 85 employees +5 more

8 metrics

Workforce size 740 employees Worldwide headcount across all functions

R&D staff 170 employees Research and development roles within total workforce

Manufacturing staff 85 employees Manufacturing roles within total workforce

Sales & marketing staff 370 employees Sales and marketing roles within total workforce

G&A staff 115 employees General and administrative roles within total workforce

CCNE1amp solid cancers >25,000 new cases/year Estimated annual U.S. CCNE1-amplified solid tumor incidence

HR+/HER2- CDK4/6i-resistant breast cancer 25,000 patients/year Estimated annual U.S. patient population

CG923308 IND timing Q1 2027 Anticipated Investigational New Drug application submission

Key Terms

forward-looking statements, Investigational New Drug (IND) application, targeted protein degradation, CDK2/Cyclin E Degrader, +2 more

6 terms

forward-looking statements regulatory

"This presentation contains “forward-looking statements” within the meaning of the federal securities laws"

Forward-looking statements are predictions or plans that companies share about what they expect to happen in the future, like estimating sales or profits. They matter because they help investors understand a company's outlook, but since they are based on guesses and assumptions, they can sometimes be wrong.

Investigational New Drug (IND) application regulatory

"Cullgen anticipates submitting an Investigational New Drug (IND) application for CG923308 in the first quarter of 2027"

An investigational new drug (IND) application is a formal request submitted to a drug regulator asking permission to begin testing a new medicine in people. It compiles lab results, manufacturing details and proposed human trial plans so regulators can judge safety before human studies start; for investors, an accepted IND is a key milestone that opens the clinical development pathway and can materially change a company’s risk profile and potential value, like getting a license to road-test a prototype.

targeted protein degradation technical

"Cullgen Was Founded on Pioneering Research in the Ubiquitin Pathway and Targeted Protein Degradation Field"

Targeted protein degradation is a drug approach that uses small molecules to mark harmful or malfunctioning proteins inside cells so the cell’s own disposal system breaks them down, rather than simply blocking their activity. For investors, it matters because this method can potentially tackle diseases that traditional drugs cannot reach, offering a new class of therapies with broad commercial and patent potential—like switching from silencing a problem to removing it entirely.

CDK2/Cyclin E Degrader medical

"CG923308 CDK2/Cyclin E Degrader for Solid Cancers"

CCNE1 amplification medical

"Indication Solid tumors with CCNE1 amplification (CCNE1amp); HR+/HER2- breast cancer with CDK4/6i resistance"

CDK4/6i resistance medical

"HR+HER2- metastatic breast cancer with CDK4/6i resistance: ~25,000 patients/year"

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Gyre Therapeutics (GYRE) disclose in this 8-K filing?

Gyre Therapeutics furnished a scientific presentation it will deliver in Shanghai. The deck outlines its integrated biopharma model, pipeline across fibrosis, inflammatory diseases and cancer, and key programs such as CG923308, and is furnished under Item 7.01 rather than filed.

What is Gyre Therapeutics’ core business focus and footprint?

Gyre Therapeutics is a fully integrated biopharmaceutical company targeting fibrosis, inflammatory diseases and cancer. It operates from a corporate headquarters in San Diego, with discovery, development, manufacturing and commercialization capabilities centered in Shanghai and Beijing to leverage cost-efficient China operations.

How many employees does Gyre Therapeutics (GYRE) have and how are they allocated?

Gyre reports about 740 employees worldwide. Approximately 170 are in R&D, 85 in manufacturing, 370 in sales and marketing, and 115 in general and administrative roles, supporting its discovery-to-commercialization activities across the United States and China.

What is CG923308 and which cancers is Gyre targeting with it?

CG923308 is a CDK2/cyclin E degrader for solid tumors with CCNE1 amplification and HR+/HER2- breast cancer resistant to CDK4/6 inhibitors. The presentation emphasizes its selective protein degradation, strong preclinical anti-tumor activity and a planned Investigational New Drug application in the first quarter of 2027.

How large is the potential patient population for Gyre’s CDK2-cyclin E degrader?

The presentation estimates more than 25,000 new CCNE1-amplified solid cancer cases annually in the United States. It also cites roughly 25,000 HR+/HER2- metastatic breast cancer patients per year with CDK4/6 inhibitor resistance as another targeted population for CG923308.

What role does Cullgen play in Gyre Therapeutics’ strategy?

Cullgen contributes pioneering work in targeted protein degradation and the ubiquitin pathway, now integrated into Gyre’s strategy following a recently announced acquisition. Its expertise underpins the CDK2-cyclin E degrader program and a broader degrader pipeline spanning multiple oncology and inflammatory indications.

How does Gyre Therapeutics plan to use its China operations?

Gyre plans to use its established, cost-efficient China operations to accelerate discovery, early validation and development of next-generation therapeutics. Facilities in Shanghai and Beijing support drug discovery, clinical development, manufacturing and commercialization to advance degrader and DAC-based therapies toward U.S. markets.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Accepted by SEC EDGAR 05/14/2026 - 05:25 PM EDT Learn about SEC filing dates

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): May 14, 2026

Gyre Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	000-51173	56-2020050
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

12730 High Bluff Drive Suite 250 San Diego, CA		92130
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: (858) 284-0115

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock		GYRE		The Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD Disclosure.

On May 15, 2026, Gyre Therapeutics, Inc. will be presenting the attached presentation at a scientific conference in Shanghai, China.

A copy of the presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein. The exhibit furnished under Item 7.01 of this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, regardless of any general incorporation language in such filing.

Item 9.01 Financial Statements and Exhibits

(d) Exhibits.

Exhibit No.	Description
99.1	Presentation, dated May 2026
104	Cover page interactive data file (embedded within the inline XBRL document)

2

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	GYRE THERAPEUTICS, INC.
Date: May 14, 2026	By:	/s/ Thomas Eastling
	Name:	Thomas Eastling
	Title:	Chief Financial Officer

3

Exhibit 99.1

 A Fully-integrated Biopharmaceutical Company Focused on Fibrosis, Inflammatory Diseases and Cancer  May 2026 

 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 of CG923308 and the potential therapeutic benefit of CG923308. 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. 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 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: At-A-Glance   Including Recently Announced Acquisition of Cullgen  Gyre Therapeutics, Inc. (Nasdaq: GYRE)  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 

 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 

 China Innovation & Validation Engine: Driving Strategic Value and Efficiency  Robust Portfolio: Fibrosis, Inflammatory Diseases, Cancer and 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  ETUARYTM  (pirfenidone)  Radiation Induced Lung InjuryLine Extension  CG620953  TYK2/JAK1 Degrader for Inflammatory   Diseases  F351  (hydronidone)  CHB-associated  Liver Fibrosis  F351   (hydronidone)  MASH-Associated  Liver Fibrosis + CHB  ETUARYTM   (pirfenidone)  Idiopathic Pulmonary  Fibrosis (IPF)  ETUARYTM   (pirfenidone)   Pneumoconiosis  Line Extension  Degrader  Efficient & cost-effective operation accelerates new pipeline development and indication expansion  Inflammatory Diseases  Cancer  Pain  Others  New Molecule Discovery & Optimization  Target   Validation  Clinical   Validation 

 Ying Luo, Ph.D.   Chief Executive Officer  Thomas Eastling  Chief Financial Officer  Weiguo Ye  Chief Operating Officer  Yue Xiong, Ph.D.   Chief Scientific Officer  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     US Management Team  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 

 7  Targeted CDK2-Cyclin E Protein Degradation for Cancer Therapy  Expanding the drug design paradigm 

 Hijacking the Ubiquitin Proteasome System to Target Undruggable Disease-causing Proteins 

 Cullgen Was Founded on Pioneering Research in the Ubiquitin Pathway and Targeted Protein Degradation Field  Cullgen Discovery  Cullgen co-founders’ discovery  TPD field Discovery  Promising phase I/II PROTAC clinical trial results reported  Discovery  of ROC1, ROC2   Discovery of CRL3 assembly mechanism  Discovery of DDB1 as CUL4 linker  Discovery  of CAND1   Cullgen founded  ALK degrader  MEK degrader  1999  2005  2001  2003  2004  2006  2007  2008  2009  2020  2010  2015  2011  2012  2013  2014  2016  2017  2018  2019  2000  2002  2021  Viral hijacking of Cullin E3  Discovery of CRL4 assembly mechanism  PROTAC proposed  Thalidomide binding to CRBN  Discovery of IMiD mechanism  CRBN- and VHL-based PROTAC  1st PROTAC in clinical trail  MDM2-recruiting PROTAC  BIRC2-recruiting PROTAC  First structure of E3-PROTAC-substrate ternary complex  2022-2025  TRK degrader   BRAF degrader   EZH2 degrader   Opto-PROTAC  EGFR degrader  PRMT5 degrader  Folate-PROTAC  CDK4/6 degrader  TF-PROTAC  AKT degrader  WDR5 degrader  NSD3 degrader  JAK degrader   KEAP1 E3 ligand  P300/CBP degrader   Novel E3 ligand  AKT PROTAC  LDH degrader  NSD2 PROTAC  EGFR degrader  Bridged PROTAC  2026  1st PROTAC approved!  Yue Xiong  Jian Jin 

 CDK2-Cyclin E Drives Solid Cancers and Breast Cancer Resistant to CDK4/6 Inhibitors  A. CDK2-cyclin E promotes cell proliferation and cancer development  B. Cyclin E is frequently amplified across multiple cancer types  C. Diverse CDK4/6i resistance converge on activation of CDK2/cyclin E  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]   [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  Analyzed by cbioportal (TCGA, PanCancer)  CDK2-cyclin E degrader blocks feedback induction of cyclin E by CDK2 inhibition and achieves sustained suppression of cell proliferation 

 CDK2-Cyclin E Degrader for Treating CCNE1-amplified Solid Cancers and Breast Cancer Resistant to CDK4/6 Inhibitors  Turner NC (2019) J Clin Oncol. PMID: 30807234; Freeman-Cook (2021) Cancer Cell PMID: 34520734; Herrera-Abreu MT (2016) Cancer Res. PMID: 27020857  Howlader (2014) J Natl Cancer Inst PMID: 24777111; Gehrchen ML et al. BJC Rep. 2024 PMID: 39516670  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;  C. Target Product Profile  A. CCNE1 highly correlates with poor patient survival  B. Deletion of CDK2/E1 re-sensitizes Palbo-resistant cells to Palbo 

 CG923308 Induces Potent and Selective CDK2-Cyclin E Degradation in Multiple Cancer Types  No degradation against known IMiD neosubstrates (GSPT1, SALL4, IKZF1/3, ZFP91, CK1α, et al)  CCNE1-amp Gastric MKN1  CG923308 (nM)  0  1  3  10  30  100  CDK2  CyclinE1  β-actin  p-Rb  DC50 (nM)  CDK2  Cyclin E1  Cyclin E2  MKN1  <0.3  0.5  <0.3  OVCAR3  0.6  30  0.9  HCC1599  0.4  1.4  0.3  MCF7  0.7  8.1  2.6  HEK293T  0.9  6.7  1.6  A. Potent degradation of CDK2 and Cyclin E  B. Selective degradation of CDK2 and Cyclin E1  Cyclin E1: not identified in HEK293T  Degrader concentration: 100-fold of DC50  CyclinE2 

 CG923308 Induced CDK2-Cyclin E Degradation Is Mediated Through Cullin, Proteasome and CRBN  CDK2  β-actin  CG923308 (nM)  Parental OVCAR3 cells  CRBN KO OVCAR3 cells  0  3  10  30  100  300  0  3  10  30  100  300  CRBN  p-Rb  1 Bortezomib: proteasome inhibitor  2 MLN4924: neddylation inhibitor  3 MG132: proteasome inhibitor  CDK2  Cyclin E1  CDK1  β-actin  MKN1  DMSO  CG923308  -  BTZ1  MLN2  MG3  -  BTZ1  MLN2  MG3  A. POI- and CRBN-dependent Ternary complex formation  B. Proteasome and Cullin-dependent degradation  C. CRBN-dependent degradation  Cyclin E1 

 CG923308 Induces Senescence, Cell Cycle Arrest and Growth Inhibition of CCNE1-amp Solid Tumors  A. CG923308 induces cell senescence and cell cycle arrest at G1 in CCNE1-amp solid tumors   B. CG923308 induces potent and selective cell growth inhibition in CCNE1-amp solid tumors   CG923308  Gastric MKN1  DMSO  β-gal  Ovarian OVCAR3  CG923308  DMSO 

 CG923308 Induces Cell Senescence and Growth Inhibition of HR+/HER2- Breast Cancer Resistant to CDK4/6 Inhibitors  Characterization of Abemaciclib-resistant MCF7 clone (by WB):  Loss of Rb  Cyclin D1 upregulation  Cyclin E1 upregulation  DMSO  Abemaciclib-resistant, Rb-deficient MCF7  Abemaciclib  β-gal  CG923308  Abemaciclib  CG923308  -  +  -  -  +  -  A. Abemaciclib-resistant, Rb-deficient MCF7 clones  B. Palbociclib-resistant, Rb-deficient MCF7 clone  Palbociclib   CG923308  -  +  -  -   +   -  Characterization of Palbociclib-resistant MCF7 clone (by RNAseq):  Loss of Rb  CDK2 upregulation  Cyclin E1 upregulation 

 CG923308 Shows Superiority Over Phase 2/3 CDK2 Inhibitors In Vitro  CG923308 overcomes feedback induction of cyclin E1  CG923308 induces deeper and more sustained pRb suppression  CG923308 induces more potent growth inhibition  CCNE1-amp Gastric MKN1 (nM)  CG923308  INCB123667  0  1  3  10  30  100  0  1  3  10  30  100  CDK2  Cyclin E1  p-Rb  GAPDH 

 CG923308 Is Orally Bioavailable Across Preclinical Species  CG923308 is orally bioavailable across preclinical species  B. Orally administrated CG923308 induces CDK2-cyclin E degradation in tumors  HCC1599 Xenograft Tumor  Vehicle  Low dose  Medium dose  High dose  CDK2  Cyclin E1  p-Rb  β-actin  Mouse  Rat  Dog  Monkey  F%  >60  >60  >20  >15 

 CDK2-Cyclin E Degrader Shows More Potent In Vivo Anti-cancer Efficacy Over Phase 2/3 CDK2 Inhibitors in CDX Models  Vehicle’ and INCB123667 treatment were conducted in a separate experiment  B. CCNE1-amp MKN1 Gastric CDX  C. CCNE1-amp HCC1599 TNBC CDX  A. CCNE1-amp OVCAR3 Ovarian CDX  Vehicle’ and INCB123667 treatment were conducted in a separate experiment  All doses were well tolerated, with no significant body weight loss observed during the studies  

 CDK2-Cyclin E Degrader Shows More Potent In Vivo Anti-cancer Efficacy Over Phase 2/3 CDK2 Inhibitors in PDX Models  All doses were well tolerated, with no significant body weight loss observed during the studies   B. Rb-deficient, CDK4/6i-resistant HR+HER2- Breast PDX   PDX was derived from a patient with HR+HER2- breast tumor resistant to Fulvestrant and CDK4/6 inhibitors  Vehicle’ and Palbociclib treatment were conducted in a separate experiment  A. Chemo-resistant CCNE1-amp TNBC PDX  PDX was derived from a patient with CCNE1-amp TNBC tumor resistant to chemo drugs 

 CDK2-Cyclin E Degrader: A Potential Therapeutic for Multiple Solid Cancers  Cullgen has developed CDK2-cyclin E dual degraders that induce highly selective and potent targeted protein degradation  CDK2-cyclin E dual degrader induces senescence, cell cycle arrest and growth inhibition of CCNE1-amp solid tumors and HR+/HER2- breast tumor resistant to CDK4/6 inhibitors  CDK2-cyclin E dual degrader shows superiority over Phase 2/3 CDK2 inhibitors in vitro: 1) Degrader overcomes feedback induction of cyclin E1; 2) Degrader induces deeper and more sustained pRb suppression; 3) Degrader induces more potent growth inhibition on CCNE1-amp tumors  CDK2-cyclin E dual degrader is orally bioavailable across preclinical species  CDK2-cyclin E dual degrader shows more potent in vivo anti-cancer efficacy over Phase 2/3 CDK2 inhibitors in CCNE1-amp ovarian, gastric and TNBC CDX/PDX models and CDK4/6i-resistant HR+HER2- breast PDX model  CDK2-cyclin E dual degrader is well-tolerated in animals with sufficient therapeutic window  CDK2-cyclin E dual degrader has potential for the treatment of solid tumors with CCNE1 amplification and HR+/HER2- breast cancers with CDK4/6i resistance  Cullgen anticipates submitting an Investigational New Drug (IND) application for CG923308 in the first quarter of 2027 

 Thank You! 

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