This white paper summarizes the current consensus of the Japanese Research Working Group for the ICH S6 & Related Issues (WGS6) on strategies for the nonclinical safety assessment of oligonucleotide-based therapeutics (ONTs), specifically focused on the similarities and differences to biotechnology-derived pharmaceuticals (biopharmaceuticals). ONTs, like biopharmaceuticals, have high species and target specificities. However, ONTs have characteristic off-target effects that clearly differ from those of biopharmaceuticals. The product characteristics of ONTs necessitate specific considerations when planning nonclinical studies. Some ONTs have been approved for human use and many are currently undergoing nonclinical and/or clinical development. However, as ONTs are a rapidly evolving class of drugs, there is still much to learn to achieve optimal strategies for the development of ONTs. There are no formal specific guidelines, so safety assessments of ONTs are principally conducted by referring to published white papers and conventional guidelines for biopharmaceuticals and new chemical entities, and each ONT is assessed on a case-by-case basis. The WGS6 expects that this report will be useful in considering nonclinical safety assessments and developing appropriate guidelines specific for ONTs.

中文翻译：

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日本研究工作组对 ICH S6 及寡核苷酸治疗非临床安全性评估相关问题的考虑：与生物制药的比较

本白皮书总结了 ICH S6 及相关问题日本研究工作组 (WGS6) 关于寡核苷酸疗法 (ONT) 非临床安全性评估策略的当前共识，特别关注与生物技术衍生疗法的异同制药（生物制药）。ONT 与生物制药一样，具有很高的物种和目标特异性。然而，ONT 具有明显不同于生物制药的特征性脱靶效应。在规划非临床研究时，ONT 的产品特性需要特殊考虑。一些 ONT 已被批准用于人类，许多目前正在进行非临床和/或临床开发。然而，由于 ONT 是一类快速发展的药物，要实现 ONT 开发的最佳策略，还有很多东西需要学习。没有正式的具体指南，因此对ONT的安全性评估主要参考已发布的白皮书和生物制药和新化学实体的常规指南进行，每个ONT都根据具体情况进行评估。WGS6 预计该报告将有助于考虑非临床安全评估和制定适用于 ONT 的适当指南。