Relationship in the knowledge plot between drug candidate and internal or external comparators with focus on preclinical efficacy and safety: comparison of efficacy and safety data for compound A and B. Both compounds have similar efficacy profiles (blue). The safety profile for compound A is different from compound B, where compound A moves towards the Meaningful Effect i.e. is expected to demonstrate safety issues. The yellow curves describe target engagement for monkey (circles) and human (triangles) and will support the holistic understanding of the relationship between efficacy and safety vs level of target engagement (similar for rat (not shown), monkey and human). The black triangles in the lower part are human Ki-values for the different receptor subtypes derived from an in vitro assay. Note that there are two efficacy profiles for each compound, which corresponds to two different ways to assess efficacy. The concept of the Knowledge Plot is demonstrated here and all details of the biomarker, study information etc. are available in the data warehouse c.f. Appendix. Legends for species: rat (star), monkey (circle), human (triangle).