Bizengri
zenocutuzumab · HER2 x HER3Cynomolgus monkey only
Epkinly: which tox species, and why?
epcoritamab · CD20 x CD3
Species
Cynomolgus monkey only
“The nonclinical toxicity profile of epcoritamab was established in a series of nonclinical safety studies in cynomolgus monkeys, the only cross-reactive toxicology species.”
Why that species
Similar affinity for human and monkey CD3/CD20; no binding to dog, pig, rat, mouse CD20; CD3 not expected in other species
“The epcoritamab binding data indicates that among the species tested, the cynomolgus monkey is the only pharmacologically relevant species for toxicology studies.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey
“We agree that the cynomolgus monkey is a pharmacologically relevant nonclinical species to assess the toxicity of epcoritamab, and general toxicology studies in other species are not warranted.”
Species: general tox
Cynomolgus monkey only (5-week study)
“The toxicity and toxicokinetics (TK) of epcoritamab were evaluated in a 5-week toxicity study in cynomolgus monkeys.”
Species: DART
Not conducted; monkey EFD study waived due to high immunogenicity in cynomolgus monkeys; weight-of-evidence assessment
“An EFD toxicity study of epcoritamab in cynomolgus monkeys was waived for phase 3 trials and registration of epcoritamab across ICH regions (FDA, EMEA, and PMDA) given the high potential for immunogenicity of epcoritamab in cynomolgus monkeys.”
Species: carcinogenicity
Not conducted (ICH S6(R1), S1A, S9)
“Carcinogenicity studies were not conducted for epcoritamab per ICHS6(R1), ICH S1A, and ICH S9 guidance.”
Surrogate used in
No surrogate used; clinical molecule in cynomolgus monkey, the only relevant species
“The epcoritamab binding data indicates that among the species tested, the cynomolgus monkey is the only pharmacologically relevant species for toxicology studies.”
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
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