Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Hemlibra: which tox species, and why?
emicizumab · FIXa x FX
Species
Cynomolgus monkey only
“Emicizumab was shown to bind similarly to the corresponding cynomolgus monkey coagulation factors, as such the cynomolgus monkey is a pharmacologically relevant species.”
Why that species
Binds/activates cynomolgus FIX/FX comparably to human; no FX activation with mouse or rat factors
“In an enzyme assay using purified Cynomolgus monkey, rat and mouse FIXa and FX, emicizumab was found to cross-react only with the corresponding clotting factors of Cynomolgus monkeys.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey (FVIII-neutralizing antibodies used only to create hemophilia models)
“Emicizumab was generally well tolerated in a 26-week toxicology study conducted in cynomolgus monkeys administered weekly SC doses of emicizumab at 1, 6, and 30 mg/kg.”
Species: general tox
Cynomolgus monkey only
“Emicizumab was generally well tolerated in a 26-week toxicology study conducted in cynomolgus monkeys administered weekly SC doses of emicizumab at 1, 6, and 30 mg/kg.”
Species: DART
Not conducted (hemophilia A is X-linked recessive)
“Animal reproductive and developmental toxicology studies were not conducted with emicizumab as hemophilia A is inherited in an X-linked recessive manner.”
Species: carcinogenicity
Not conducted (no pharmacologically relevant rodent species)
“Carcinogenicity studies were not conducted due to lack of a pharmacologically relevant rodent species.”
Surrogate used in
No surrogate used; clinical molecule tested in cynomolgus monkey
“Emicizumab was shown to bind similarly to the corresponding cynomolgus monkey coagulation factors, as such the cynomolgus monkey is a pharmacologically relevant species.”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Chimpanzee (only relevant species, limited non-terminal studies) plus mouse with murine surrogate
Columvi
glofitamab · CD20 x CD3Cynomolgus monkey only
Elrexfio
elranatamab · BCMA x CD3Cynomolgus monkey only
Epkinly
epcoritamab · CD20 x CD3Cynomolgus monkey only
Imdelltra
tarlatamab · DLL3 x CD3Cynomolgus monkey (pivotal); mouse surrogate muS757 for EFD and 1-month study
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)No relevant species; in vitro human cell/tissue assays only
Korjuny
catumaxomab · EpCAM x CD3No relevant species; limited single-dose mouse, rat, one cynomolgus; BiLu mouse surrogate
Lunsumio
mosunetuzumab · CD20 x CD3Cynomolgus monkey only
Lynozyfic
linvoseltamab · BCMA x CD3Cynomolgus monkey only
Ordspono
odronextamab · CD20 x CD3Cynomolgus monkey only
Removab
catumaxomab · EpCAM x CD3No relevant species; in vitro human cells plus mouse surrogate (BiLu); limited single-dose rodent/monkey
Rybrevant
amivantamab · EGFR x METCynomolgus monkey only
Talvey
talquetamab · GPRC5D x CD3Cynomolgus monkey only (tool molecule for pivotal tox); no rodent tox
Tecvayli
teclistamab · BCMA x CD3Cynomolgus monkey only (rabbit used for SC local tolerance only)
Vabysmo
faricimab · VEGF-A x Ang-2Cynomolgus monkey only for pivotal tox (rabbit dropped after early studies)
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Cynomolgus monkey only