Antibody Therapeutic Development with An Integrated Platform Combines Immunized Libraries, Synthetic Libraries, AI/ML Guided Leads Optimization, and HT IgG Production at Twist Bioscience. 

Antibody drugs are a promising and rapidly growing component of the therapeutic landscape. The success of antibody therapeutics is largely driven by its specificity and selectivity in contrast to the off-targets liabilities of small molecule drugs. To advance antibody drug discovery, Twist integrated multiple techniques and platforms including synthetic and immunized libraries, artificial intelligence and machine learning (AI/ML), and High Throughput IgG Production (HT IgG) to discover, optimize, produce, and characterize antibody drug candidates against a wide range of inflammatory and immune-oncology targets to assist in generating leads for downstream pre-clinical and clinical campaigns. Wnt signaling pathway has been known to play important regulatory roles in tumorigenesis. Dickkopf-1 (DKK1) is an endogenous protein known to over-express in tumor microenvironments and can block Wnt/β-catenin signaling by interrupting Wnt-FZD-LRP interactions. Previous studies have shown the anti-tumor effect of anti-DKK1 antibodies in multiple different cancers including esophagogastric cancer, lung cancer, prostate cancer, etc. Here, we would like to show how Twist uses our integrated platform to identify functional anti-DKK1 antibody drug candidates through screening of hundreds of hits enriched from phage display and AI/ML affinity maturation. This platform can also be easily expanded to any other “difficult to target” drug targets.