Target Safety Assessment

Modern drug discovery requires a thorough understanding of target biology, its connection to disease, and the potential adverse effects of target engagement.  A target safety assessment (TSA) helps identify unintended adverse consequences of target modulation and confirms, as well as characterizes, unavoidable on-target toxicities to support informed program decisions. By evaluating risks and providing tailored mitigation strategies, a TSA guides projects through the drug discovery and development pipeline and enables teams to anticipate, monitor, and manage potential clinical adverse events through actionable safety recommendations. Evotec provides a broad range of in silico, in vitro, and in vivo solutions to support this process, helping to reduce costly late-stage failures and giving teams the best chance of success.

To deliver the most comprehensive and accurate target safety assessment for your project, we have developed a proprietary in-house tool that integrates AI/ML with automated data retrieval and scoring. The platform provides access to any target required for in-depth exploration and is continuously updated to incorporate the latest research and clinical findings.

• Consolidates all relevant biological and clinical data for rapid insight generation
• Combines advanced analytics with scientific expertise to build predictive models to assess the likelihood of adverse reactions
• Supports tailored mitigation strategies for early de-risking
• Enables more informed decision making throughout the drug development process

Each target safety assessment is unique and curated to the specific project requirements and queries. However, key aspects contained within each are:

• Target Expression, homology, target physiological function and human/animal genetic phenotypes
• Summary of potential liabilities with impact and probability scoring
• Analysis of competitor therapeutics and current clinical trials (if available)
• Full target safety assessment report with actionable de-risking strategies

The summary of potential liabilities and de-risking strategies is arguably the most critical component of the target safety assessment. It represents the culmination of all available data, distilled into key toxicological concerns associated with the target of interest. Beyond identifying these liabilities, we apply evidence-based ranking to assess both the probability and impact of each risk, enabling a more tailored and strategic approach to mitigation. Our assessments also include recommended follow-up assays aligned with each liability, helping to shape a robust de-risking plan. This comprehensive insight equips discovery teams to navigate development with confidence and avoid late-stage surprises.

Target safety assessment (TSA) is a structured evaluation of the potential safety risks associated with modulating a target of interest during drug discovery. It helps identify unavoidable on-target toxicities and provides mitigation and derisking strategies.

Because very few targets are safe to modulate for a given indication or modality. It is essential to know if a target is required for normal function in critical tissues like the heart or brain. TSA identifies these risks early, reducing the chance of unexpected toxicities in clinical trials and costly late-stage development failures through actionable safety recommendations.

TSA will be unique and tailored to your specific requirements. However, it will always include:

• Target expression, homology, and known or hypothesized physiological functions
• Human and animal genetic phenotypes
• The published scientific literature on the target relevant to potential adverse events
• Analysis of competitor therapeutics and current clinical trials, when available
• A summary of potential liabilities, contextualized by your specific indication or modality
• Scoring of liabilities: probability of occurrence and potential impact on the drug development program
• Tailored derisking and mitigation strategies.

Anyone involved in drug discovery or target validation: project leaders who need to understand the safety implications of a target; drug discovery teams seeking to prioritize safe targets; research scientists or toxicologists guiding study design; or business development teams assessing investment risk.

Ideally during target selection or before significant investment in lead optimization or preclinical studies, so that safety concerns can be anticipated and addressed as early as possible. However, TSA can also be updated later, at any stage of the drug development program, for example, before entering GLP toxicology or clinical testing, as more data become available.

TSA identifies risks from the target itself, before a specific drug is even chosen. Toxicology assays examine the safety of a specific compound in vitro or in animal models. TSA helps predict whether any compound acting on-target is likely to be inherently risky.

More than half of attrition of drug candidates is due to preclinical or clinical toxicity. TSA allows you to anticipate adverse effects, provides derisking strategies and helps you prioritize safer targets.