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Built on the RenLite® platform, BCG048 utilizes common light chain technology to eliminate heavy/light chain mispairing, ensure seamless assembly, simplify manufacturing, and provide a developable antibody backbone for the ITGB6 × B7-H3 dual-target ADC design.
BCG048 integrates vcMMAE (DAR=2) with our proprietary BLD1102 linker–payload system (BCPT02, DAR=4)—a highly potent topoisomerase I (TOP1) inhibitor with greater cytotoxic activity than DXd, addressing the limitations of single-payload ADCs.
The preclinical data supporting BCG048 include target co-expression analysis, dual-payload conjugation feasibility, dual-payload pharmacokinetics, bispecific antibody backbone internalization, and antitumor efficacy in a colorectal PDX model, supporting the development of BCG048 as an ITGB6 × B7-H3 dual-payload bispecific ADC for broad potential solid tumor indications.
Figure 1. Co-expression analysis of ITGB6 and B7-H3 in solid tumors based on TCGA transcriptomic data. Expression levels of ITGB6 and B7-H3 were evaluated using log2-transformed TPM values from the TCGA database. These data demonstrate a positive correlation between the two targets, supporting the rationale for evaluating ITGB6 × B7-H3 dual-targeting strategies in selected solid tumors, including esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), bladder urothelial carcinoma (BLCA), lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and pancreatic adenocarcinoma (PAAD).
Figure 2. Antigen binding analysis of a trastuzumab-based dual-payload ADC in HCC1954 cells. The trastuzumab-vcMMAE-BLD1102 ADC (red line) retained HER2 binding activity comparable to both unconjugated trastuzumab and the single-payload trastuzumab-vcMMAE ADC, confirming that dual-payload conjugation does not compromise antigen affinity.
Figure 3. Pharmacokinetic (PK) profile of a vcMMAE and BLD1102 dual-payload ADC. Following a single intravenous administration at 3 mg/kg, plasma concentrations of the dual-payload ADC, single-payload controls, and free payloads were quantified over time. The dual-payload ADC (yellow line) exhibited a PK profile comparable to that of the single-payload controls, confirming sustained systemic ADC exposure after dual-payload conjugation with vcMMAE and BLD1102.
Figure 4. Internalization kinetics of the BCG048 ITGB6 × B7-H3 bispecific antibody backbone in tumor cells. Internalization was evaluated across HCC70, HCC1954, and BXPC-3 cells with different ITGB6 and B7-H3 expression levels. The BCG048 bsAb-5 clone (green line) demonstrated rapid, progressive internalization over time, outperforming single-target ITGB6 or B7-H3 parental antibody analogs and mutant controls, confirming enhanced internalization driven by the ITGB6 × B7-H3 bispecific antibody design.
Figure 5. Antitumor efficacy of BCG048 dual-payload ADC in the BP0847 colorectal PDX model. BCG048 (red line) showed superior antitumor efficacy compared with single-payload ADCs (A) and benchmark ADCs (B), supporting the antitumor potential of the ITGB6 × B7-H3 dual-targeting and dual-payload ADC design in this preclinical model.
Biocytogen welcomes partnership discussions to further evaluate the development potential of BCG048.
BCG048 is designed as a first-in-class dual-payload bispecific ADC (bsAD2C) asset. While clinical evidence shows that single-payload ADCs often fail to eliminate all tumor clones, BCG048 addresses tumor heterogeneity by simultaneously targeting two overexpressed solid tumor antigens: ITGB6 and B7-H3. Furthermore, it delivers two complementary cytotoxic payloads to provide a multi-dimensional attack, allowing it to outperform benchmark ADC comparators in vivo.
A dual-payload ADC overcomes treatment resistance through a "Dual-Strike Strategy" that conjugates two complementary toxins onto a single antibody to deliver a multi-dimensional attack. This design ensures that even if some cells are naturally resistant to one toxin, the second "mechanistically distinct" toxin can still kill them. Additionally, it prevents resistance by maintaining antitumor activity even if the tumor becomes resistant to one of the payload mechanisms, ultimately delivering synergistic potency and higher efficacy than co-administering separate treatments.
Targeting both ITGB6 and B7-H3 provides a strategic advantage through complementary biology, pairing ITGB6's role in tumor invasion and immune exclusion with B7-H3's immune checkpoint suppression. This dual targeting reduces antigen escape to cover tumor heterogeneity and offers enhanced selectivity since both targets show low expression in normal tissues. Additionally, while B7-H3 is a highly competitive target in the industry, adding ITGB6 provides mechanistic uniqueness and a strong positioning advantage.
The BCG048 bsAD2C utilizes a unique combination of two distinct payloads to enable complementary mechanisms of action. It pairs vcMMAE, a validated microtubule inhibitor with DAR=2, with the proprietary BLD1102 linker-payload system, which delivers the novel TOP1 inhibitor payload BCPT02 with DAR=4. Notably, this proprietary BCPT02 payload is highly potent and demonstrates greater cytotoxic activity than standard DXd (an exatecan derivative).
A major challenge in developing bispecific antibodies is the complex manufacturing process. The RenLite® platform significantly improves bispecific ADC manufacturing by utilizing a fully human common light chain backbone. This innovative structural design effectively eliminates chain mispairing, which ensures seamless assembly and greatly simplifies the overall manufacturing process.
BCG048 is being evaluated as a next-generation bispecific ADC for ITGB6/B7-H3-expressing solid tumors. Potential development areas include non-small cell lung cancer (NSCLC), pancreatic, triple-negative breast cancer (TNBC), colorectal, gastric cancers, where dual targeting may help improve tumor coverage and ADC payload delivery.
Blog: Overcoming Tumor Resistance and Heterogeneity: The Power of Dual-Payload Bispecific ADCs. Published February 26, 2026.
