ICE Bioscience Posters

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Cardiac safety liability assessment is essential in drug development to prevent arrhythmias like torsades de pointes (TdP), which can cause sudden death. Traditional ICH S7B and E14 guidelines focus on hERG blockade and QT prolongation, but these lack specificity, leading to high attrition or missed risks. The Comprehensive in vitro Proarrhythmia Assay (CiPA), launched in 2013 by FDA, academia, and industry, shifts to a mechanistic paradigm. It integrates in vitro ion channel assays, in silico modeling, hiPSC-CM evaluations, and clinical ECGs to predict proarrhythmia accurately, reducing animal use and improving efficiency. Validated with 28 reference compounds, CiPA enhances specificity.

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In drug discovery, proactive toxicological risk assessment of candidate compounds is crucial for avoiding clinical-stage failure and post-market withdrawal. However, traditional preclinical safety evaluation strategies have significant limitations: in vivo animal studies exhibit low human relevance (translatability) due to significant species differences and face dual pressures of ethics and cost; while conventional in vitro binding assays are inadequate for predicting functional biological effects. Notably, approximately 75% of clinical adverse drug reactions (ADRs) originate from dose-dependent off-target effects, highlighting an urgent need for more accurate early-risk identification tools. To address these challenges, the IQ DruSafe consortium—a preeminent alliance of global pharmaceutical companies—has championed the enhancement of preclinical predictive power through the expansion and refinement of secondary pharmacology screening strategies. This study is aligned with this initiative and aims to investigate the implementation of an advanced in vitro secondary pharmacology screening system utilizing functional assay formats. By generating richer pharmacological information beyond mere binding affinity, this strategy seeks to enable a more accurate and earlier identification of potential safety liabilities, thereby providing highly translatable safety insights for the optimization of lead compounds.

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Dual-payload antibody-drug conjugates (ADCs) represent a next-generation therapeutic strategy designed to overcome tumor heterogeneity and drug resistance by delivering two distinct payloads with synergistic potential. This study aimed to identify an optimal dual-payload combination to address the challenge of therapeutic resistance in colorectal cancer (CRC), focusing on inhibitors of DNA damage response (DDR) pathways.

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In drug discovery, proactive toxicological risk assessment is critical for mitigating clinical-stage attrition and post-market withdrawals. Traditional preclinical strategies face significant limitations: in vivo models often exhibit poor human translatability due to species differences, alongside ethical and cost constraints, while conventional in vitro binding assays fail to capture functional biological effects. Given that approximately 75% of clinical adverse drug reactions (ADRs) are dose-dependent and originate from off-target interactions, the demand for more predictive early-risk identification tools is pressing. Addressing this need, the IQ DruSafe consortium—a preeminent alliance of global pharmaceutical companies—has advocated for enhancing predictive power by expanding and refining secondary pharmacology screening. Aligned with this initiative and the SLAS Europe 2026 theme of “Shaping the Future of Life Sciences and Automation,” this study investigates the implementation of an advanced, automation-driven in vitro screening system utilizing functional assay formats. By integrating high-throughput automation platforms, such as automated liquid handling systems, this strategy moves beyond mere binding affinity to generate rich, quantitative pharmacological data with high precision and reproducibility. The purpose is to leverage this automated, functionally-oriented screening to enable a more accurate and earlier identification of potential safety liabilities, thereby providing highly translatable insights for lead compound optimization and reshaping the paradigm of early safety assessment.

The ICESTP SAFETYPANEL™ 77 Dose Response platform provides a comprehensive functional screening strategy that integrates single-point primary screening with quantitative dose-response (curve-based) profiling. This strategy is supported by a broad suite of mechanism-relevant functional assay technologies, including FLIPR calcium flux assay, HTRF, ADP-Glo, fluorescence polarization (FP), and other mechanism-relevant functional formats. The entire workflow exemplifies the convergence of functional biology and advanced automation. The process is fully automated—from initial compound handling via Echo and Firefly systems, through functional readouts on platforms like BMG. This integrated approach ensures exceptional efficiency, reproducibility, and data richness. By accelerating the safety profiling process, minimizing manual error, and delivering mechanistically insightful, quantitative datasets (e.g., IC₅₀/EC₅₀), the platform enables more reliable optimization of candidate compounds early in the drug discovery pipeline.