Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Lunsumio: which tox species, and why?
mosunetuzumab · CD20 x CD3
Species
Cynomolgus monkey only
“Cynomolgus monkey was selected as the appropriate animal species for assessing the nonclinical safety, pharmacokinetic (PK), and pharmacodynamic (PD) properties of mosunetuzumab and 2H7v16/40G5c.”
Why that species
Cross-reacts with CD20 and CD3 in human and cynomolgus monkey, not rodents; comparable CD3 binding and B-cell killing potency
“2H7v16/40G5c displays the same properties as mosunetuzumab, as it cross-reacts with CD20 and CD3 in both humans and cynomolgus monkeys, but not in rodents.”
Surrogate molecule
Yes: functionally equivalent E. coli-made precursor 2H7v16/40G5c used in early monkey studies; pivotal 26-week study used mosunetuzumab
“Mosunetuzumab is produced from Chinese hamster ovary (CHO) cells; the functionally equivalent antibody, referred to as 2H7v16/40G5c and the proof-of-concept (POC) molecule, referred to as 2H7v16/UCHT1v9, were produced from E. coli.”
Species: general tox
Cynomolgus monkey only
“Cynomolgus monkey was selected as the appropriate animal species for assessing the nonclinical safety, pharmacokinetic (PK), and pharmacodynamic (PD) properties of mosunetuzumab and 2H7v16/40G5c.”
Species: DART
Not conducted; NHP EFD and pre/postnatal study waived on weight of evidence (FDA agreed)
“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993). In a written communication from the FDA dated 14 June 2018, the Agency agreed to the waiver request.”
Species: carcinogenicity
Not conducted (oncology indication, ICH S6(R1))
“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”
Surrogate used in
No species-specific surrogate; functionally equivalent analogue 2H7v16/40G5c (same human/monkey cross-reactivity) used in some studies
“2H7v16/40G5c displays the same properties as mosunetuzumab, as it cross-reacts with CD20 and CD3 in both humans and cynomolgus monkeys, but not in rodents.”
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
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