Entry into the critical pre-clinical ‘Good Laboratory Practice (GLP)’ stage of toxicology testing triggers significant R&D investment yet >20% of AstraZeneca’s potential new medicines have stopped for safety reasons in this GLP phase alone. How could we avoid at least some of these costly failures? An analysis of historical ‘stopping toxicities’ showed that > 50% were attributable to target organ toxicities emerging within two weeks of repeat dosing or to acute cardiovascular risks. By frontloading 2 week repeat dose toxicity studies and a comprehensive assessment of cardiovascular safety, we anticipate a potential 50% reduction in attrition in the GLP phase. This will reduce animal use overall, save significant R&D costs and improve drug pipeline quality.