Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Lynozyfic: which tox species, and why?
linvoseltamab · BCMA x CD3
Species
Cynomolgus monkey only
“Overall, data indicate that linvoseltamab bound human and Cynomolgus monkey BCMA, but not rat or mouse BCMA.”
Why that species
Binds human and monkey BCMA (monkey lower affinity, KD 24.6 nM vs 437 pM human) and CD3 on both; no rat/mouse BCMA binding
“Overall, data indicate that linvoseltamab bound human and Cynomolgus monkey BCMA, but not rat or mouse BCMA.”
Surrogate molecule
No surrogate; clinical molecule (REGN5458) tested in cynomolgus monkey
“Two repeat dose toxicology studies were performed by the applicant, (Study R5458-TX-17179 and Study r5458-tx-20118).”
Species: general tox
Cynomolgus monkey only
“The first study was conducted in male and female monkeys once weekly for 5 weeks at doses of 0.1, 1, or 10 mg/kg IV infusion with a subsequent recovery period of 12.”
Species: DART
Not conducted (weight-of-evidence risk assessment)
“No animal reproductive or developmental toxicity studies have been conducted with linvoseltamab.”
Species: carcinogenicity
Not conducted (ICH S9, advanced malignancies)
“As linvoseltamab is intended for use in patients with advanced malignancies, carcinogenicity studies were not conducted with linvoseltamab, consistent with ICH S9 guideline Nonclinical Evaluation of Anticancer Pharmaceuticals.”
Surrogate used in
No surrogate used; clinical molecule tested in cynomolgus monkey
“Safety pharmacology evaluations were integrated into a GLP-compliant repeat-dose toxicology study conducted in Cynomolgus monkeys using linvoseltamab”
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
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