Liver Stage
Two compounds (OSM-S-218 (MMV669844) and OSM-S-175 (MMV670944), below) were evaluated (by Stephan Meister from UCSD) vs. Pb liver schizonts and found to possess low activity compared to their blood stage potencies. (Note that the original Series 4 briefing document stated the series had "no activity against Winzeler’s Pb liver stage" but there were no associated data to support this statement).
The former compound (OSM-S-218 (MMV669844)) was evaluated with an unknown enantiomeric composition. This compound was subsequently resolved (see also this GH Issue) to give MMV897709 (rac - intentionally synthesised as rac, so different code to MMV669844) and MMV1557952 (S) and MMV1557951 (R). Evaluation of these (by Sabine Ottilie, Jenya Antonova and Korina Eribez in 2017) revealed differing blood stage potencies for the enantiomers, so it is possible that the liver stage activity arises also from one of the enantiomers.) But the overall data from the more recent data from studies in the Winzeler lab were found to be confusing, possibly because of an issue with the resolution itself, and the conclusion from these more recent experiments remains unclear.
Assuming there is indeed low activity, then this clearly distinguishes Series 4 from a structurally similar imidazopyrazine series discovered by Novartis (associated discussion), that possesses activity against all liver stages in several Pf species. The two series demonstrate no cross-resistance and are thought to possess distinct mechanisms of action (PfATP4 vs. PI4K). To complement the existing data for Series 4 vs. liver schizonts, OSM-S-218 and -175 were progressed into the same Pc hypnozoite assay used to evaluate the Novartis series (it is possible that the data were not in fact generated/obtained).