46 TWENTYFOURSEVENBIOPHARMA Issue 3 / October 2025 Introduction: The rising complexity of small molecule development The development of small-molecule therapeutics has never been more complex. Pharmaceutical researchers are faced with molecules with higher molecular weight and increasing 3D character. At the same time, regulatory expectations are rising, market competition is intensifying, and patient needs demand more rapid development timelines. In this context, leveraging early-phase, data-driven strategies is essential for accelerating drug development while mitigating risk. Once a target molecule has been identified, determining an optimal synthetic route as early as possible can help ensure long-term process feasibility and reduce overall risk. By integrating advanced tools from the earliest stages of development, drug developers can not only identify synthetic routes more quickly but also incorporate real-world data into route design. Modern approaches allow researchers to comprehensively explore possible synthetic processes, determining the most efficient, scalable, and reliable route before substantial resources are invested in preclinical or clinical manufacturing. Synthetic processes that perform well in the lab may present challenges when scaled to preclinical or commercial volumes. For instance, a highyielding reaction may be safe at laboratory scale, but scaling it for commercial production introduces significant safety and regulatory challenges, requiring specialized controls and equipment. By keeping downstream needs in mind from the outset, pharmaceutical developers can avoid costly process adjustments and delays during later stages of development. Designing smarter routes: AI-enabled route scouting Retrosynthetic analysis is a foundational step in small-molecule development. While traditional methods focus on identifying the shortest, most reliable route, modern approaches consider additional constraints such as raw material availability, cost, and scalability. Lonza’s Advanced Synthesis Business Platform integrates AI-enabled computer-aided synthesis planning (CASP) with real-world supply chain and pricing data. This approach allows drug developers to assess routes not only for theoretical efficiency LONZA
RkJQdWJsaXNoZXIy MjY2OTA4MA==