Abstract C071: ICESTP SAFETYPANEL™: From Off-Target Identification to Clinical Risk Management

Abstract Background and Purpose: A core challenge in translational medicine is bridging the gap between preclinical prediction and clinical outcomes. Data indicates that 75% of Type A adverse drug reactions (ADRs), stemming from dose-dependent off-target toxicity, directly lead to late-stage development termination or market withdrawal. To address this translational bottleneck, ICE Bioscience developed an in vitro drug safety assessment platform, ICESTP SAFETYPANEL™ 44, which contains 44 screening models closely to safety, having systematically quantified off-target risks across over 800 structurally diverse compounds, significantly enhancing preclinical safety prediction. Its upgraded panels, ICESTP SAFETYPANEL™ 77 and PLUS, further integrate cell biology and pharmacological safety profile. Building upon ICESTP 44, they enrich the panel with a broader range, establishing a more comprehensive in vitro pharmacological safety profiling. This enables the development of customized dosing strategies for translational pipelines, ultimately reducing attrition rates in the clinical phase. Methods: The ICESTP 77 and PLUS platforms employ a dual strategy of single-point screening and dose-response curve screening. Utilizing techniques such as FLIPR, HTRF, reporter gene and neurotransmitter transporter uptake assays, they enable functional evaluation of panel targets including GPCRs, ion channels, transporters, and enzymes. A key technological breakthrough is the integration of an automated system incorporating Echo acoustic liquid handling, Firefly microplate processors, and BMG multi-mode readers for high-throughput dose-response testing. Leveraging this, we performed functional dose-response testing on compounds such as pergolide, amitriptyline, and osimertinib using the ICESTP 77 and PLUS platforms. Results: The ICESTP SAFETYPANEL™ dose-response platforms provide robust support for addressing translational safety barrier. Its functional assays precisely quantify interaction potency with both therapeutic and non-target receptors, identify non-linear dose-toxicity relationships to enable personalized testing protocols, and effectively circumvent traditional false-positive bias via physiological ATP kinase milieu simulation (1 mM) and solubility correction. The high-throughput capabilities driven by the integrated automation (Echo®/Firefly®/BMG®) significantly accelerate the translation of preclinical safety data into clinical decision-making. Conclusions: The ICESTP SAFETYPANEL™ framework reshapes the translational medicine defense through secondary pharmacology. Systematic evaluation of off-target across key target classes enhances the clinical predictability of Type A ADRs. Its mechanistic safety profiles underpin individualized dosing regimens, proactively mitigating clinical attrition. This establishes a reliable pathway from in vitro safety pharmacology to clinical risk management. Citation Format: Zhiying Nie, Qiang Xia, Yanan Zhao, Mingyang Yuan, Ziye Cui, Meihui Shi, Tiejun Bing. ICESTP SAFETYPANEL™: From Off-Target Identification to Clinical Risk Management [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C071.