Incorporation of target safety review in drug discovery

Abstract

Ensuring the safety of new pharmaceuticals and therapies is paramount in drug discovery. Takeda’s Discovery Toxicology plays a crucial role in reducing safety-related risks by focusing on the quality of drug discovery targets. This involves identifying potential toxicities early in the development phase, enabling the mitigation of risks before they impact later stages of drug development. The Target Safety Review (TSR) initiates the Target Safety Assessment (TSA) process, providing a strategic assessment of safety concerns arising from target modulation. The TSR types range from comprehensive evaluations to simplified versions, assessing on-target and off-target effects, project background, biological information, and chemistry. Importantly, the TSR includes risk ranking and de-risking plans. Risks are ranked based on their probability and impact, enabling informed decision-making throughout the drug development process. This minireview discusses several case studies at Takeda, illustrating the importance of early risk identification. Of course, challenges remain, such as the appropriate timing of TSR creation, limited human on-target information, the need for effective risk assessment methods, incorporation of safety indicators into pharmacological studies, and addressing specific background risks in patient populations. Nonetheless, utilizing the TSR and TSA processes ensures a streamlined and safer drug development journey and provides a comprehensive approach to effectively address potential safety risks.