Abstract 3150: InVEST44™ is a cost-effective <i>in vitro</i> safety panel that identifies off-target effects in early-stage drug discovery

Abstract Drug development costs exceed $172m and increase to over $500m when clinical trial failures are considered (Sertkaya 2024, DOI: 10.1001/jamanetworkopen.2024.15445). It can take 20 years to bring a drug to market so it is critical to identify safety liabilities early in the discovery process to ensure valuable time and money are not invested in preclinical and clinical trials. In vitro safety panels, such as InVEST44™, can identify potential toxicities of drugs cost-effectively during early-stage drug development. This is particularly relevant as, between 2006 and 2023, the proportion of venture capital investments in early-stage drug discovery has decreased from 50% to 16% while increasing for later stage from 20 to 54% (The Biopharma Industry Investment Report 2015. Biotechnology Innovation Organization; Larka 2024, Trends in Venture Capital Funding for Biopharma Startups. GlobalData). This highlights a trend towards expensive, high-risk but potentially lucrative, clinical trials and away from early drug discovery. The goal is to demonstrate that early-stage in vitro safety panels are fiscally and scientifically critical steps in drug development to identify off-target effects before advancing drugs to animal testing and clinical trials. InVEST44™ is an in vitro safety panel designed to identify off-target effects of lead compounds for oncology and other therapeutic areas in early-stage drug development, ensuring a more efficient path from discovery to clinical trials. It comprises 44 industry standard, high risk targets based on Bowes et al. (2012; DOI: 10.1038/nrd3845), including GPCRs, transporters, ion channels, nuclear receptors and enzymes. Various assay types are utilized, including radioligand binding, fluorescence polarization, enzymatic activity, cell reporter, calcium mobilization and electrophysiology assays. We identified 20 drug candidates from 17 failed clinical oncology trials between 2001 and 2025, all terminated because of reported severe adverse effects (clinicaltrials.org). These were screened at 10 µM in InVEST44™: 17 drugs elicited &amp;gt;50% effect on at least 1 target, including 8 with 4+ target interactions and one interacting with 15 safety targets. This study demonstrates the importance of in vitro safety panels, such as InVEST44™, by identifying off-targets effect of lead compounds before pursuing time-consuming and expensive animal testing and potentially failed clinical trials. Data from such panels are increasingly being provided to enhance IND applications (Scott, 2022, DOI: 10.1016/j.vascn.2022.107205). In summary, by providing cost-efficient, early-stage identification of off-target effects by lead compounds, in vitro safety panels, such as InVEST44™, have become integral components of drug discovery and warrant increased early-stage consideration and investment in the future. Citation Format: Julian R. Wooltorton,Afsara Ahona,Nicole Barbacane,Alex D'Andrea,Justin Lansberry,Cindy Lay,Paige Miller,John Ries,Jamin Steffen,Patricia Valentine. InVEST44™ is a cost-effective in vitro safety panel that identifies off-target effects in early-stage drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3150.