Blincyto
blinatumomab · CD19 x CD3Chimpanzee (only relevant species, limited non-terminal studies) plus mouse with murine surrogate
Bizengri: which tox species, and why?
zenocutuzumab · HER2 x HER3
Species
Cynomolgus monkey only
“The cynomolgus monkey was utilized as the only pharmacologically relevant species for toxicity testing, in view of cross reactivity of MCLA-128 with the HER2/HER3 targets in this species.”
Why that species
Binds human and monkey HER2/HER3 (98-99% sequence identity); anti-HER2 Fab does not bind rodent HER2
“Together, these results support the use of cynomolgus monkeys as the pharmacologically relevant species for zenocutuzumab toxicity assessment.”
Surrogate molecule
No surrogate; clinical molecule (MCLA-128) tested in cynomolgus monkey
“Toxicokinetic (TK) characteristics of MCLA-128 (zenocutuzumab) were studied as part of single and repeated dose toxicity studies in cynomolgus monkeys, the pharmacologically relevant species.”
Species: general tox
Cynomolgus monkey only
“The cynomolgus monkey was utilized as the only pharmacologically relevant species for toxicity testing, in view of cross reactivity of MCLA-128 with the HER2/HER3 targets in this species.”
Species: DART
Not conducted; literature-based weight-of-evidence assessment (HER2/HER3 role in embryo-fetal development)
“The Applicant did not conduct reproductive or embryo-fetal developmental toxicology studies with zenocutuzumab. Rather, the Applicant provided a literature-based weight-of-evidence (WOE) assessment of the potential reproductive toxicity of zenocutuzumab based on its mechanism of action”
Species: carcinogenicity
Not conducted (not appropriate for antibody-based therapies)
“Carcinogenicity and genetic toxicology studies with zenocutuzumab were not conducted as they are generally not appropriate for antibody-based therapies.”
Surrogate used in
No surrogate used; clinical molecule tested in cynomolgus monkey
“Toxicokinetic (TK) characteristics of MCLA-128 (zenocutuzumab) were studied as part of single and repeated dose toxicity studies in cynomolgus monkeys, the pharmacologically relevant species.”
Same question, other multispecifics
Columvi
glofitamab · CD20 x CD3Cynomolgus monkey only
Elrexfio
elranatamab · BCMA x CD3Cynomolgus monkey only
Epkinly
epcoritamab · CD20 x CD3Cynomolgus monkey only
Hemlibra
emicizumab · FIXa x FXCynomolgus 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