Strategies to Address Toxicities in the Discovery Space

Later in the candidate selection phase, short-term or pilot toxicology studies in rodents and nonrodents are typically conducted. When toxicities arise in animal studies, three primary questions come to mind (i) what is the nature, severity, monitorability, reversibility and H of the toxicity, (ii) is the toxicity likely to translate to humans, and (iii) what is the likely mechanism of toxicity (MOT), target related or off target The answers to these critical questions will shape the safety strategy for the project (Fig. 46.1)  

Likely to achieve clinical activity without DLTs 

FIGURE 46.1 Algorithm to inform decision-making in compound progression. 

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