Blenrep: which tox species, and why?

“The only pharmacologically relevant species able to capture on-target BCMA-related toxicities for belantamab mafodotin is the cynomolgus monkey. To capture any non-specific toxicities related to the payload (MMAF), general toxicology and ocular toxicology studies were conducted in the Wistar Han rat and New Zealand White Rabbit.”

“Binding of belantamab mafodotin to human and monkey BCMA has been demonstrated using Biacore and the affinity shown to be within 2-fold”

“Selected evaluations were conducted with cys-mcMMAF, the active cytotoxic moiety, and GSK2857914, the parent, unconjugated afucosylated anti-BCMA antibody, to further characterize the overall nonclinical profile of belantamab mafodotin.”

“Additionally, tissue cross-reactivity studies showed antigen-specific staining of belantamab mafodotin in human spleen.”

“Repeat dose toxicity evaluation was conducted for belantamab mafodotin, cys-mcMMAF and GSK2857914 in rats and cynomolgus monkeys, and in rabbits focusing on the ocular findings.”

“Reproductive and developmental studies have not been conducted since cytotoxic drugs such as belantamab mafodotin which target rapidly dividing cells, particularly in the bone marrow, are expected to be embryo/ fetotoxic and teratogenic. This position is consistent with ICH S9 guidance.”

“No carcinogenicity studies have been conducted to support the development of belantamab mafodotin.”

“Selected evaluations were conducted with cys-mcMMAF, the active cytotoxic moiety, and GSK2857914, the parent, unconjugated afucosylated anti-BCMA antibody, to further characterize the overall nonclinical profile of belantamab mafodotin.”