AACR 2026 | Bioits ADAM9 ADC
Biocytogen announced preclinical data for its ADAM9-targeted ADC, BCG029, at AACR 2026. Utilizing the fully human RenLite platform and ADAM9 gene knockout (KO) mice, they developed an ADAM9 antibody clone—Anti-ADAM9 monoclonal antibody (Anti-ADAM9 mAb). This antibody specifically binds to the membrane-proximal region of ADAM9-L (long isoform) but does not recognize its secreted isoform, ADAM9-S. The clone precisely targets ADAM9 with no cross-reactivity to other members of the ADAM family, a specificity validated in ADAM9 KO cell lines. Furthermore, the Anti-ADAM9 mAb demonstrates broad binding activity across a range of tumor cell lines and possesses efficient internalization capabilities. Crucially, in peripheral blood mononuclear cell (PBMC) binding assays, the antibody showed extremely low binding activity to myeloid cells compared to benchmark antibodies. This finding suggests that the Anti-ADAM9 mAb may reduce off-target interactions, highlighting its potential for higher specificity in therapeutic applications.
Upon conjugation with vcMMAE, the ADC demonstrated superior efficacy in multiple PDX models compared to benchmark antibodies conjugated with the same payload. Subsequently, conjugating this antibody with the novel topoisomerase I inhibitor BLD1102 yielded BCG029, which also exhibited potent anti-tumor activity in PDX models. Currently, in vivo studies of BCG029 are ongoing to further evaluate its performance.
These findings underscore the therapeutic potential of BCG029 in targeting ADAM9-positive solid tumors. By specifically targeting ADAM9, BCG029 is expected to provide safer and more effective treatment options for patients with ADAM9-expressing tumors.
BCG029 is assembled from three components:
- Anti-ADAM9 mAb
: Fully humanized antibody.
- BLD1102 (Novel Payload)
: A novel topoisomerase I inhibitor (TOP1i) independently developed by Biocytogen, belonging to the camptothecin derivative class. This payload has high membrane permeability, can produce a bystander killing effect, and carries a lower risk of ocular toxicity compared to microtubule inhibitors (such as MMAE).
- BCPT02 (Linker)
: Acts as the "lock" stably connecting the antibody and toxin, ensuring the ADC does not prematurely release the toxin in the bloodstream.
The final product, BCG029, has a drug-to-antody ratio (DAR) of approximately 8.
Immunohistochemistry (IHC) staining validation confirmed that ADAM9 exhibits high-level expression in various solid tumors, including breast cancer, esophageal cancer, lung cancer, colorectal cancer, pancreatic cancer, and gastric cancer.
In cell line binding experiments across more than twenty types of cancers, including lung, gastric, breast, prostate, and pancreatic cancers, Biocytogen's Anti-ADAM9 antibody demonstrated broad yet specific binding capability—showing the strongest binding to cells such as prostate cancer (DU-145, PC-3) and fibrosarcoma (HT-1080), moderate binding to most solid tumor cell lines (lung, gastric, breast, pancreatic), and extremely weak binding to hematological tumor cell lines.
The antibody recognizes the EC1 domain (extracellular region near the membrane-proximal area) of ADAM9.
And does not bind to other family members ADAM8/12/15/19/28.
The antibody exhibits strong specific binding affinity.
The antibody shows excellent internalization effects.
Disclaimer: This article is intended solely to convey scientific research and popular science information and does not constitute any recommendation or advice for treatment methods or medications. If you feel unwell, please strictly follow medical advice for medication and treatment.
Source: New Drug Idle Notes
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