Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Vabysmo: which tox species, and why?
faricimab · VEGF-A x Ang-2
Species
Cynomolgus monkey only for pivotal tox (rabbit dropped after early studies)
“She agreed, as the Applicant proposed, that the monkey alone should be used in the planned 6-month chronic toxicity study.”
Why that species
100% VEGF sequence homology and comparable Ang-2 binding affinity in monkey; rabbit unsuitable (severe toxicity, ADA)
“The monkey was selected as the most relevant species based on 100% sequence homology (VEGF) and binding affinity (Ang-2) comparable to humans.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey (and rabbit in early studies)
“Faricimab (RO6867461) bound to full length Ang 2 with high affinity across species including human, cynomolgus monkey, rabbit, and mouse, measured by Surface Plasmon Resonance (SPR).”
Species: general tox
Cynomolgus monkey (up to 6 months); rabbit (up to 2 weeks)
“Repeat-dose toxicity studies of up to 2 weeks in rabbits and up to 6 months in cynomolgus monkeys have been conducted.”
Species: DART
Cynomolgus monkey (EFD); pre/postnatal study not feasible due to ADA and exposure loss
“A pre- and postnatal development study could not be conducted in cynomolgus monkeys due to ADA formation and exposure loss observed in general toxicology studies preventing sufficient systemic exposure with faricimab in such a study.”
Species: carcinogenicity
Not conducted (no relevant binding to rodent VEGF-A)
“No standard rodent carcinogenicity studies have been conducted as faricimab showed no relevant binding to mouse or rat VEGF-A.”
Surrogate used in
No surrogate used; clinical molecule in cynomolgus monkey, the only cross-reactive species
“In summary, no target-related toxicological changes were observed up to the highest doses tested with faricimab including the evaluation of repeat-dose toxicity, male and female fertility, and embryofetal development using cynomolgus monkeys, the only feasible species cross-reactive to faricimab.”
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
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)
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Cynomolgus monkey only