DLL3 × B7-H3 Bispecific ADC (BCG025)

Asset ID: BCG025
Targets: DLL3 × B7-H3
  • Aliases:
  • DLL3: SCDO1; B7-H3: CD276, 4Ig-B7-H3, B7H3, B7RP-2
  • Modality:
  • Bispecific ADC (BsADC)
  • Payload Design:
  • BLD1102 linker–payload system containing BCPT02, a TOP1 inhibitor payload
  • Development Stage:
  • Preclinical
  • Indications:
  • Small cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), neuroendocrine prostate cancer (NEPC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC)
  • Key Differentiation:
  • Combines DLL3-mediated tumor selectivity with broader B7-H3-driven tumor coverage to enhance internalization, expand patient coverage, and achieve superior antitumor efficacy versus single-target ADC approaches
  • Partnership Opportunity:
  • Available for licensing and co-development
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  • DLL3 × B7-H3 Bispecific ADC Asset Highlights
  • Preclinical Data
  • Partnership Opportunities
  • FAQs

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    BCG025: A DLL3 × B7-H3 Bispecific ADC Designed to Address Tumor Heterogeneity

    Dual-Target Strategy for SCLC and Other Tumors

    • DLL3-directed tumor selectivity: DLL3 is a clinically validated tumor-associated antigen (TAA) with elevated expression in small cell lung cancer (SCLC; up to 85%) and neuroendocrine tumors (NETs; 20–40%), with little to no expression in normal tissues.
    • B7-H3-mediated tumor coverage: B7-H3 is another clinically validated ADC target broadly overexpressed in SCLC and other tumor types, enabling strategic engagement of B7-H3-positive tumor cells to support intratumoral cytotoxic payload delivery.
    • Dual-target strategy: By combining DLL3 specificity with broader B7-H3 coverage, BCG025 is engineered to address intratumoral antigen heterogeneity, preventing antigen escape within the tumor microenvironment (TME).
    • Competitive Differentiation: BCG025 integrates two clinically validated SCLC-targeting arms in a bispecific ADC format, supporting a de-risked development rationale, enhanced internalization, stronger antitumor efficacy, and broader patient coverage than conventional single-target ADC approaches.

    RenLite® Fully Human Common Light Chain Antibody Backbone

    Built on the RenLite® platform, BCG025 utilizes common light chain technology to eliminate heavy/light chain mispairing, ensure seamless assembly, simplify manufacturing, and provide a developable antibody backbone for the DLL3 × B7-H3 bispecific ADC drug development.

    Proprietary BLD1102 Linker–Payload Design for ADC Drug Development

    BCG025 is conjugated with Biocytogen’s proprietary BLD1102 linker–payload system containing BCPT02, a topoisomerase I (TOP1) inhibitor payload designed to drive potent ADC-mediated cytotoxicity in solid tumor drug development.

    • Payload-driven cytotoxic coverage: BCPT02 combines high payload potency with strong bystander killing to eliminate both target-positive and neighboring tumor cells.
    • Developability-oriented linker design: BLD1102 linker is designed for superior hydrophilicity, controlled payload release, and high circulation stability, enhancing ADC developability and therapeutic performance.

    Excellent Preclinical Performance

    • BCG025 demonstrated effective binding and enhanced internalization in DLL3/B7-H3-expressing SCLC cells, supporting dual-target engagement and intracellular payload delivery (Figure 1 & Figure 2).
    • BCG025 demonstrated robust antitumor efficacy across dual-positive and B7-H3 single-positive CDX/PDX models, supporting the bispecific format and DLL3-independent activity of the B7-H3 arm (Figure 3).
    • BCG025 showed favorable stability and tolerability in a preliminary non-human primate (NHP) study, with an HNSTD of ≥20 mg/kg. Laboratory analyses and toxicokinetic assessments are in progress.

    Potential Indications

    BCG025 is being evaluated as a DLL3/B7-H3-directed bispecific ADC drug development asset for small cell lung cancer (SCLC). Additional potential development areas include neuroendocrine carcinoma (NEC), neuroendocrine prostate cancer (NEPC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), and osteosarcoma (OS).

    Preclinical Data Highlights Supporting BCG025 DLL3 × B7-H3 Bispecific ADC Drug Development

    The preclinical data package supporting BCG025, generated from Biocytogen internal studies, includes dual-target binding, enhanced internalization, robust antitumor efficacy across CDX and PDX models with various DLL3 and B7-H3 expression profiles, and supportive stability and tolerability data in preliminary NHP studies. Together, these data support the development of BCG025 as a differentiated DLL3 × B7-H3 bispecific ADC for small cell lung cancer (SCLC) and other B7-H3-expressing tumors.

    BCG025 Demonstrates Strong Binding in DLL3/B7-H3-Expressing SCLC Cells

    Binding curves showing BCG025 activity in NCI-H524 and SHP-77 small cell lung cancer cells compared with DLL3- and B7-H3-directed benchmark analogs and monovalent antibodies.

    Figure 1. Antigen binding analysis of the DLL3 × B7-H3 bispecific antibody in NCI-H524 and SHP-77 SCLC cells. Across the tested SCLC cell lines, BCG025 showed binding activity comparable to the B7-H3 benchmark analog and higher than the DLL3 benchmark analog. A similar binding pattern was observed relative to the corresponding monovalent antibody controls, supporting effective dual-target tumor cell engagement.
    In addition, affinity characterization demonstrated high-affinity binding and cross-reactivity to both human and cynomolgus monkey DLL3 and B7-H3, supporting translational development.

    DLL3 × B7-H3 Antibody Backbone Shows Enhanced Internalization in SCLC Cells

    Internalization curves showing BCG025 uptake in NCI-H524 and SHP-77 small cell lung cancer cells compared with DLL3- and B7-H3-directed benchmark analogs.

    Figure 2. Internalization analysis of the DLL3 × B7-H3 bispecific antibody in NCI-H524 and SHP-77 SCLC cells. Under the evaluated assay conditions, BCG025 showed greater internalization activity than the single-target benchmark analogs. These findings support efficient cellular uptake through the bispecific antibody format and its suitability for intracellular payload delivery.

    BCG025 Demonstrates Antitumor Efficacy Across CDX and PDX Models

    Tumor growth curves comparing BCG025 with monovalent antibody ADC controls in NCI-H524 and NCI-H69 DLL3/B7-H3 dual-positive SCLC CDX models.

    Figure 3A. Antitumor efficacy analysis of BCG025 in DLL3/B7-H3 dual-positive SCLC CDX models. In the NCI-H524 and NCI-H69 models, BCG025 showed comparable or stronger tumor growth inhibition than the corresponding monovalent ADCs. These results support the functional contribution of the DLL3 × B7-H3 bispecific design in tumors co-expressing both targets.

    Tumor growth curves comparing BCG025 with a matched B7-H3 benchmark ADC in NCI-H1975 CDX and BP0818 PDX models with B7-H3 expression and absent or limited DLL3 expression.

    Figure 3B. In vivo antitumor efficacy analysis of BCG025 in B7-H3-positive, DLL3-negative tumor models. In the NCI-H1975 lung CDX and BP0818 breast PDX models, BCG025 conjugated with BLD1102 (DAR~8) showed greater tumor growth inhibition than the matched B7-H3 benchmark ADC under the tested conditions. These findings indicate that the B7-H3 arm retains functional activity in the absence of DLL3 expression and may broaden the activity of BCG025 to B7-H3 single-positive tumors.
    In addition, BCG025 showed favorable developability and tolerability in a preliminary NHP dose-range-finding study, with an HNSTD of at least 20 mg/kg. Laboratory analyses and toxicokinetic assessments are ongoing.

    Explore BCG025 Partnership Opportunities

    Biocytogen welcomes partnership discussions to further evaluate this DLL3 × B7-H3 bispecific ADC asset.

    Frequently Asked Questions (FAQs) About BCG025 DLL3 × B7-H3 Bispecific ADC

    1. What makes BCG025 a differentiated DLL3 × B7-H3 bispecific ADC?

    BCG025 differentiates itself by combining DLL3-mediated tumor selectivity with broader B7-H3-driven tumor coverage in a single bispecific ADC. This design supports enhanced internalization, broader patient coverage, and superior preclinical antitumor efficacy versus single-target ADC approaches under the tested conditions.

    2. How does the DLL3 × B7-H3 dual-target strategy address tumor heterogeneity?

    DLL3 is highly expressed in SCLC with limited normal-tissue expression, whereas B7-H3 is more broadly expressed across SCLC and other solid tumors. By engaging DLL3-positive, B7-H3-positive, and dual-positive tumor populations, BCG025 reduces reliance on a single antigen and broadens tumor-cell coverage.

    3. What linker–payload system is used in BCG025?

    BCG025 is conjugated with Biocytogen's proprietary BLD1102 linker–payload system containing BCPT02, a topoisomerase I (TOP1) inhibitor payload. BCPT02 combines high cytotoxic potency with strong bystander killing to eliminate both target-positive and neighboring tumor cells. The BLD1102 linker is engineered for superior hydrophilicity, controlled payload release, and high circulation stability, supporting ADC developability and sustained therapeutic performance.

    4. How does the RenLite® platform support the development of BCG025 as a bispecific ADC?

    BCG025 is built on the RenLite® fully human common light chain antibody platform. The common light chain design eliminates heavy/light chain mispairing, ensures correct bispecific antibody assembly, simplifies downstream manufacturing, and supports overall ADC developability — addressing a key CMC challenge in bispecific ADC engineering.

    5. Which indications are targeted for BCG025 development?

    BCG025 is currently at the preclinical stage, with a primary focus on SCLC, supported by the expression profiles of DLL3 and B7-H3. Based on the dual-target design rationale and the B7-H3 arm's DLL3-independent activity, BCG025 may also have broader development potential in B7-H3-expressing tumors, including neuroendocrine carcinoma (NEC), neuroendocrine prostate cancer (NEPC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), and osteosarcoma (OS).