Joenja: genotox, carcinogenicity and repro: done or skipped?

“Leniolisib was not genotoxic in the in vitro Ames assay, in vitro chromosomal aberration assay in human lymphocytes, or micronucleus assays in TK6 cells ( in vitro ) and rats ( in vivo ).”

“Leniolisib was not carcinogenic in the 6-month carcinogenicity study in Tg.rasH2 transgenic mice at doses up to 80 mg/kg/day.”

“In animal reproduction studies, oral administration of leniolisib to pregnant rats and rabbits during the period of organogenesis at exposures approximately 2-6 times the MRHD on an AUC basis, produced embryofetal toxicity including malformations ( see Data ).”

“Leniolisib was found to inhibit hERG channel currents in hERG-transfected HEK cells with an IC50 of 11.9 μM. Consistent with this finding, single dose leniolisib (150 mg/kg, oral) administration induced QTcI (QT interval, individual correction) prolongation in two separate monkey telemetry studies.”