Suzhou, China, April 20th, 2026—CStone Pharmaceuticals (“CStone,” HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, immunology, inflammation, and other key disease areas, today announced that the Company presented the latest preclinical data for three proprietary pipeline assets at the American Association for Cancer Research (AACR) Annual Meeting (from April 17 to 22), including CS5007 (EGFR/HER3 ADC), CS5006 (ITGB4 ADC), and CS5008 (DLL3/SSTR2 ADC).

CStone's Proprietary ADC Technology Platform

All three antibody-drug conjugates (ADCs) presented at AACR – CS5007 (EGFR/HER3 ADC), CS5006 (ITGB4 ADC), and CS5008 (DLL3/SSTR2 ADC) – are developed utilizing CStone’s proprietary ADC technology platform, which incorporates the following core features:

• High Stability & Precise Payload Release: The platform utilizes CStone’s proprietary CSL20 linker, a hydrophilic construct designed for enhanced stability in circulation. Payload release is triggered selectively through a tandem cleavage mechanism involving the synergistic action of β-glucuronidase and cathepsin.
• Potent Payload: Each ADC employs exatecan, a clinically validated and highly potent topoisomerase I inhibitor with a strong bystander effect and reduced sensitivity to multidrug resistance.

CS5006 – ITGB4 Targeting ADC

Integrin β4 (ITGB4) exclusively pairs with Integrin α6 (ITGA6) to form the α6β4 heterodimer, a receptor for the basement membrane protein laminin. ITGB4 is highly expressed on the surface of various solid tumors, including CRC, NSCLC, HNSCC and ESCC, while its expression in normal tissues is low. Distinct from other β integrins, ITGB4 features a unique 1,000-amino acid cytoplasmic domain that may facilitate a rapid antigen turnover. Furthermore, ITGB4 integrates with and amplifies key signaling cascades—including ErbB2, PI3K, FAK/Akt, and c-Met—thereby driving tumor progression. It also upregulates the expression of PD-L1 and mediates anti-PD-1 resistance via MEK/ERK signaling.

CS5006 is a novel ADC targeting ITGB4, composed of a humanized anti-ITGB4 IgG1 antibody conjugated via a highly stable, hydrophilic CSL20 linker (with tandem-cleavage technology) to a clinically validated exatecan payload, with an average DAR of 4.

Notes:^*Beta-glucuronidase exclusively functions within the cell and is highly expressed in tumor cells.

Key Highlights:

1. Superior Molecular Stability

The linker-payload system of CS5006 demonstrates superior in vitro plasma stability to GGFG-DXd-based model ADCs targeting ITGB4, with less than 0.6% free payload released after 7 days of incubation in human or monkey serum, indicating a low risk of off-target toxicity.

2. Rapid and Deep Internalization

CS5006 triggers rapid and deep internalization on ITGB4-positive tumor cells.

Notes: polatuzumab and polatuzumab-CLS20-Exa, isotype control antibody and isotype control ADC; Fabfluor-pH Red, a pH-sensitive dye used for real-time dynamic monitoring of antibody internalization.

3. Potent and Specific In Vitro Anti-tumor Activity

CS5006 exhibits nanomolar-level, antigen-dependent cytotoxic activity against tumor cell lines with high ITGB4 expression and sensitivity to exatecan in vitro. Its killing potency is significantly positively correlated with the expression level of ITGB4 on the tumor cell surface.

Notes: H1975-OsiR, an osimertinib-resistant cell line which was established by stably expressing human EGFR harboring the L858R, T790M, and C797S mutations; ABC, antibody binding capacity; TI, therapeutic index, calculated as follows: TI=IC₅₀ of Polatuzumab-CSL20-Exa / IC₅₀ of CS5006.

4. Significant Bystander Killing Effect

CS5006 demonstrates an excellent bystander killing effect. Supernatants from ITGB4-positive tumor cells incubated with CS5006 induced significant cytotoxicity in ITGB4-negative tumor cells.

Notes: TAs, test articles; conditioned DMEM medium collected from TA-treated HARA cell cultures; conditioned 1640 medium collected from TA-treated KU-19-19 cell cultures; detection concentration: 8 nM for all TAs.

5. Broad-Spectrum and Deep In Vivo Anti-Tumor Activity

CS5006 demonstrated potent and broad-spectrum tumor growth inhibition (TGI) activity in CDX models covering multiple tumor types, including NSCLC, BC, CRC, SCCHN, urothelial cancer (UC), ESCC, and gastric cancer (GC).

Notes: 1) Relative tumor growth volume (TGv, %) was calculated according to the following equation: if T_i<T₀, TGv (%) = 100 × (T_i -T₀)/T₀, and if not, TGv (%) = 100 × (T_i -T₀)/(V_i-V₀); based on the equation, we defined TGv<0 as tumor regression; 2) Best regression, the best TGv after the 1st cycle of treatment (7 days); 3) The dose of H86.2-DXd (DAR8) was determined as the dose level providing molar-equivalent payload carried by 5 or 10 mg/kg CS5006; 4) n.d. not determined yet, in progress.

6. Favorable PK Profile and Safety

In NHPs, CS5006 exhibits a favorable PK and safety profile, with a half-life of approximately 3.5 days and a tentative HNSTD of 45 mg/kg.

CS5006 is a highly promising first-in-class ADC targeting ITGB4, combining broad-spectrum and potent anti-tumor activity with favorable safety and PK profiles. Preclinical studies have demonstrated rapid, deep internalization and potent, specific killing of ITGB4-positive cells, with bystander-mediated elimination of ITGB4-negative cells, thereby exhibiting broad-spectrum and robust in vivo anti-tumor activity in xenograft models. In NHPs, CS5006 exhibits a favorable HNSTD and half-life. Furthermore, it also demonstrates impressive CMC profiles, including high antibody yield, strong ADC stability, and favorable developability. Collectively, the preclinical data provide strong support for the clinical development of CS5006.

CStone expects to initiate the IND application for CS5006 in the second half of 2026.

About CStone

CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, autoimmune/inflammation, and other key disease areas. Dedicated to addressing patients’ unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 21 new drug applications covering 9 indications. The company’s pipeline is balanced by 16 promising candidates, featuring antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization.

For more information about CStone, please visit: www.cstonepharma.com.

IR contact: ir@cstonepharma.com

PR contact: pr@cstonepharma.com

Forward-looking statements

The forward-looking statements made in this article only relate to events or information as of the date when the statements are made in this article. Except as required by law, we undertake no obligation to update or publicly revise any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. All statements in this article are made on the date of publication of this article and may change due to future developments.

Disclaimer: only for communication and scientific use by medical and health professionals, it is not intended for promotional purposes.