Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Talvey: which tox species, and why?
talquetamab · GPRC5D x CD3
Species
Cynomolgus monkey only (tool molecule for pivotal tox); no rodent tox
“Toxicology studies were not conducted in rodents due to the lack of talquetamab or JNJ-64024701 cross reactivity in these species.”
Why that species
Talquetamab binds cyno CD3 but not cyno GPRC5D (~100-fold lower activity); tool molecule binds cyno GPRC5D and CD3
“Due to the lack of cross reactivity of talquetamab to cynomolgus monkey GPRC5D, the tool molecule (JNJ-64024701) was developed.”
Surrogate molecule
Yes: monkey-cross-reactive GPRC5DxCD3 tool molecule JNJ-64024701 (same CD3 arm, different GPRC5D arm)
“The tool molecule has the same CD3 binding arm but different GPRC5D binding arm as talquetamab, and binding and in vitro functional activity against cGPRC5D-expressing cells consistent with talquetamab against hGPRC5D-expressing cells.”
Species: general tox
Cynomolgus monkey only (pivotal 1-month GLP study with tool molecule JNJ-64024701)
“The toxicity and toxicokinetics (TK) of JNJ-64024701 were evaluated in a GLP-compliant 1-month repeatdose toxicity study in cynomolgus monkeys”
Species: DART
Not conducted: monkey EFD/enhanced PPND with talquetamab or tool molecule judged not feasible (weight-of-evidence)
“Based on a weight-of-evidence risk assessment (Mod2.6.6/Sec6.2), an embryo-fetal development or enhanced pre- and postnatal development study in cynomolgus monkeys with talquetamab or the tool molecule would not be feasible nor further inform pregnancy risk to multiple myeloma patients.”
Species: carcinogenicity
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted with talquetamab. As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
Surrogate used in
Yes: monkey-cross-reactive tool molecule JNJ-64024701 used for monkey toxicology
“Due to the lack of cross reactivity of talquetamab to cynomolgus monkey GPRC5D, the tool molecule (JNJ-64024701) was developed.”
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
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