SUZHOU, China, April 19, 2026 /PRNewswire/ — CStone Pharmaceuticals (“CStone,” HKEX: 2616) presented the latest preclinical data for three proprietary pipeline assets at the American Association for Cancer Research (AACR) Annual Meeting (April 17 to 22). The assets include CS5007 (EGFR/HER3 ADC), CS5006 (ITGB4 ADC), and CS5008 (DLL3/SSTR2 ADC).
CStone’s ADC technology platform
All three antibody-drug conjugates (ADCs) presented at AACR are developed using CStone’s proprietary ADC technology platform, which includes:
- High stability and precise payload release: The platform uses CStone’s proprietary CSL20 linker, designed as a hydrophilic construct to enhance stability in circulation. Payload release is triggered selectively via a tandem cleavage mechanism involving β-glucuronidase and cathepsin.
- Potent payload: Each ADC uses exatecan, a clinically validated topoisomerase I inhibitor with a strong bystander effect and reduced sensitivity to multidrug resistance.
CS5007 (EGFR/HER3 bispecific ADC)
CS5007 is designed to dual-target EGFR and HER3, which are frequently co-overexpressed in human epithelial malignancies. The company said dual targeting aims to address adaptive resistance driven by compensatory HER3 signaling and HER-family heterodimerization that can limit the long-term benefit of single-target EGFR therapies.
CS5007 is a bispecific ADC comprising an anti-EGFR and HER3 human IgG1 antibody, the CSL20 linker, and exatecan (Exa) as the payload, with a drug-to-antibody ratio (DAR) of approximately 4.
Key preclinical highlights
- Superior molecular stability: In vitro plasma stability testing showed free payload release below 0.5% after 7 days of incubation, outperforming the DS-8201 (trastuzumab deruxtecan) benchmark.
- Dual signaling pathway blockade: Western blot analysis using the naked antibody J17 (the antibody component of CS5007) assessed signal blocking across tumor cell lines under ligand-stimulated conditions (TGF-α/EGF and/or NRG1 β1). The company reported inhibition of downstream Akt and MAPK pathways. It said J17 abrogated HER3/Akt signaling in A431 and FaDu cells even under ligand-stimulated conditions, while SI-B001 (the naked antibody of BL-B01D1) failed to interrupt HER3/Akt signaling in those cells.
- Rapid and deep internalization: Using Incucyte real-time live-cell imaging with pH sensor dye, CS5007 was reported to be efficiently and rapidly internalized across multiple tested tumor cell lines (A431, BxPC-3, FaDu, SW620, and MDA-MB-468) in a concentration-dependent manner and trafficked to lysosomes. The company also reported that in SW620 cells with low EGFR expression, CS5007 maintained efficient drug delivery via HER3-mediated internalization.
- Potent, broad-spectrum in vitro anti-tumor activity: In CellTiter-Glo assays across six human tumor cell lines, CS5007 showed nanomolar-level, antigen-dependent cytotoxicity across NSCLC, SCC, CRC, SCCHN, pancreatic cancer (PANC), and breast cancer (BC).
- Significant bystander killing effect: In a co-culture system using NCI-H1568 (antigen-positive) and NCI-H524 (antigen-negative) cells, CS5007 was reported to eliminate both antigen-positive and adjacent antigen-negative tumor cells, addressing tumor heterogeneity.
In vivo activity, PK/PD, and safety
- Broad in vivo anti-tumor activity: CS5007 inhibited tumor growth in cell line-derived xenograft (CDX) models across NSCLC, CRC, BC, SCCHN, and SCC.
- Activity in resistant models: CS5007 was reported effective in osimertinib-resistant H1975 (EGFR C797S mutation) and achieved tumor clearance in SW620 (low EGFR/high HER3) where the comparator BL-B01D1 showed no meaningful activity.
- PK/PD advantages vs. BL-B01D1 (FaDu CDX): At 5 mg/kg, exposure (AUC) was comparable between the two ADCs, but tumor regression was significantly greater with CS5007 (p < 0.05). CS5007 also maintained a half-life of approximately 20 hours across dose levels versus approximately 10 hours for BL-B01D1 at 5 mg/kg.
- Safety and tolerability: In non-human primates (NHPs), CS5007 showed favorable metabolic stability with a half-life of approximately 2 days. In human FcRn transgenic mice, the half-life was approximately 2.5–8 days. GLP toxicology reported the highest non-severe toxic dose (HNSTD) as 30 mg/kg, with no lethal toxicity observed; skin toxicity occurred only at the high-dose level.
Planned clinical development
CStone plans to initiate the Investigational New Drug (IND) application for CS5007 in the first half of 2026. The planned CS5007-101 study is described as a monotherapy dose-escalation and expansion trial to evaluate safety and a recommended phase II dose (RP2D) in patients with advanced solid tumors. The company said the study will enroll approximately 70 adult patients with advanced solid tumors that have progressed on or are ineligible for standard treatment or have no effective treatment options.
CS5006 (ITGB4 targeting ADC)
CS5006 targets integrin β4 (ITGB4), which pairs with integrin α6 (ITGA6) to form the α6β4 heterodimer, a receptor for laminin. CStone said ITGB4 is highly expressed on the surface of multiple solid tumors, including CRC, NSCLC, HNSCC, and ESCC, while expression in normal tissues is low. The company also said ITGB4’s cytoplasmic domain may facilitate rapid antigen turnover and that ITGB4 signaling can integrate with pathways including ErbB2, PI3K, FAK/Akt, and c-Met, and can upregulate PD-L1 and mediate anti-PD-1 resistance via MEK/ERK signaling.
CS5006 is described as a novel ADC using a humanized anti-ITGB4 IgG1 antibody conjugated via the CSL20 linker (with tandem-cleavage technology) to exatecan, with an average DAR of 4.
Key preclinical highlights
- Superior molecular stability: The linker-payload system showed less than 0.6% free payload release after 7 days of incubation in human or monkey serum, compared with GGFG-DXd-based model ADCs targeting ITGB4.
- Rapid and deep internalization: CS5006 was reported to trigger rapid and deep internalization on ITGB4-positive tumor cells.
- Potent and specific in vitro anti-tumor activity: The company reported nanomolar-level, antigen-dependent cytotoxicity against tumor cell lines with high ITGB4 expression and exatecan sensitivity, with killing potency positively correlated with ITGB4 surface expression.
- Significant bystander killing effect: CS5006-treated ITGB4-positive tumor cell supernatants were reported to induce cytotoxicity in ITGB4-negative tumor cells.
- Broad-spectrum in vivo anti-tumor activity: CS5006 demonstrated tumor growth inhibition in CDX models across NSCLC, BC, CRC, SCCHN, urothelial cancer (UC), ESCC, and gastric cancer (GC).
PK and safety
- Favorable PK and safety in NHPs: CS5006 was reported to have a half-life of approximately 3.5 days and a tentative HNSTD of 45 mg/kg.
CStone said it expects to initiate the IND application for CS5006 in the second half of 2026.
CS5008 (DLL3/SSTR2 bispecific ADC)
CStone said DLL3 and SSTR2 are highly overexpressed in small cell lung cancer (SCLC) and neuroendocrine tumors/carcinomas (NETs/NECs). The company reported DLL3 is overexpressed in more than 70% of SCLC and 64% of NECs patients, while SSTR2 is overexpressed in over 50% of SCLC and approximately 90% of G1/G2 NETs patients. It said dual targeting may help address intra- and inter-tumoral heterogeneity in SCLC and NETs/NECs and potentially broaden the addressable patient population.
The company also noted that despite initial sensitivity to chemotherapy and/or radiotherapy, most SCLC patients develop therapeutic resistance within one year. It said evidence links SCLC heterogeneity and plasticity to distant metastases and chemoresistance.
CS5008 is described as a bispecific ADC comprising an anti-DLL3 and SSTR2 human IgG1 antibody, the CSL20 linker, and exatecan (Exa) as the payload, with a DAR of approximately 4.
Key preclinical highlights
- Excellent in vitro serum stability: After 7 days at 37°C in human and cynomolgus monkey serum, CS5008 showed toxin release below 0.5%.
- Rapid and deep internalization: CS5008 was reported to trigger rapid and deep internalization on SSTR2- and/or DLL3-positive tumor cells, with higher internalization rates in SCLC tumor cells compared with mono-specific ADC counterparts.
- Potent, antigen-dependent in vitro killing: The company reported efficient and specific killing of DLL3- or SSTR2-expressing tumor cells, with killing correlated with antigen expression (SSTR2+DLL3).
- Broad-spectrum in vivo anti-tumor activity: In SCLC CDX models, CS5008 was reported to induce tumor regression after a single dose across models with different antigen expression levels. It also reported CS5008 outperformed DLL3-CSL20-Exa in the H446 (DLL3-negative SCLC) CDX model, suggesting potential to address tumor heterogeneity.
- PK and safety profile in cynomolgus monkeys: CS5008 was reported to have a half-life of approximately 14 days and a provisional HNSTD of 60 mg/kg, with no lethal toxicity observed.
Strategy to address subtype switching resistance
CStone said CS5008’s dual targeting may address resistance associated with therapy-driven molecular subtype switching in SCLC (e.g., from SCLC-A to SCLC-N). The company cited that subtype switching occurred in approximately 50% of patients during therapy, and that recent data showed 75% (3/4) of SCLC-A converted to SCLC-N versus 100% (2/2) of SCLC-N stability. It also said SCLC-N is associated with NEUROD1-driven SSTR2 overexpression, and that a bispecific DLL3/SSTR2 ADC may offer a strategy to overcome resistance resulting from subtype switching.
CStone said it expects to initiate the IND application for CS5008 in the second half of 2026.
About CStone
CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on research and development of therapies for oncology, autoimmune/inflammation, and other key disease areas. The company said it has launched four innovative drugs and secured approvals for 21 new drug applications covering nine indications. CStone said its pipeline includes 16 promising candidates spanning antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies, and precision medicines.
Forward-looking statements
The company’s forward-looking statements relate to events or information as of the article’s publication date. Except as required by law, CStone said it undertakes no obligation to update or revise forward-looking statements after the date of publication.
