"In a pre-clinical study of AMG176 (Caenepeel et al, Cancer Discovery 2018), ‘176 was deemed to be well tolerated with no overt toxicities observed, as determined by changes in mouse body weight. A pre-clinical study (Brennan et al, Blood, 2018) of S63845 (Servier/Novartis), in humanized MCL-1 mouse models demonstrated increased respiration and inability to ambulate at doses of 25mg/kg, although the exact causes of death could not be determined. In an earlier study (Wang et al, Genes & Dev, 2013) of mice who had MCL-1 expression deleted, the mice developed rapidly fatal dilated cardiomyopathy within 2-3 weeks of MCL-1 suppression; this syndrome was associated with reduced contractility, fibrosis, and mitochondrial dysfunction. These findings were supported by a subsequent study (Thomas et al, Genes & Dev, 2013) in which MCL-1 knockout mice developed cardiac hypertrophy, contractile dysfunction, and early mortality."
How did this escape Cindy Afshari’s and Hugo Vargas’ impervious assessment and decision making? Bunch of tools...
If Cindy's bonus was tied to the number of molecules she moved to clinical development, the FDA will be investigating in 5, 4, 3, 2... Hey Novartis, you're not the only company that plays fast and loose with the rules.
