Blincyto
blinatumomab · CD19 x CD3Chimpanzee exposure (Cmax 0.9-1.36 ng/mL) higher than human Css at 9 and 28 µg/day; no NOAEL or multiple stated
Ziihera: what safety margin did regulators accept?
zanidatamab · HER2 x HER2 (biparatopic)
Safety margin at NOAEL
Monkey NOAEL 150 mg/kg: exposure ~10-fold above clinically relevant exposure
“In repeat-dose toxicity studies in cynomolgus monkeys (28DTOX and 13WTOX), no mortality or signs of acute toxicity was noted following the first administration of zanidatamab at dose levels up to 150 mg/kg resulting in exposure multiples approximately 10-fold higher than clinically relevant exposure.”
NOAEL / key findings
NOAEL 150 mg/kg QW x13 weeks (highest dose); only non-adverse soft/watery feces, mild BUN increase
“No adverse effects were observed at any dose tested (up to 150 mg/kg QW) for animals in either the 8-week or 13-week dosing cohorts.”
Same question, other bispecifics
Columvi
glofitamab · CD20 x CD3Monkey exposure below clinical: AUC multiples 0.03-0.28 in studies without obinutuzumab pretreatment
Elrexfio
elranatamab · BCMA x CD3Monkey NOAEL/LOEL 0.3 mg/kg exposure well below human exposure (0.1x or 0.2x)
Epkinly
epcoritamab · CD20 x CD3Monkey SC NOAEL 10 mg/kg: 5x clinical steady-state AUC; IV 1 mg/kg exposure equal to clinical AUC
Hemlibra
emicizumab · FIXa x FXMonkey NOAEL (30 mg/kg, 26-week) ~11x human AUC at 3 mg/kg QW
Korjuny
catumaxomab · EpCAM x CD3No margin: surrogate BiLu mouse NOAEL (0.2-3.0 µg/kg) equivalent to the clinical catumaxomab dose (1.43 µg/kg)
Lunsumio
mosunetuzumab · CD20 x CD3No NOAEL; CRS and infections in monkeys at exposures 0.008-1.84x human AUC
Rybrevant
amivantamab · EGFR x METMonkey AUC at 120 mg/kg 5x human AUC at the 1050 mg clinical dose
Tecvayli
teclistamab · BCMA x CD3Monkey NOEL 30 mg/kg IV weekly: 22x AUCtau, 48x Cmax vs human 1.5 mg/kg SC weekly
Vabysmo
faricimab · VEGF-A x Ang-2Ocular NOAEL 0.5 mg/eye (6-month monkey): exposure margin only around 1x human
Bizengri
zenocutuzumab · HER2 x HER3Not stated in public reviews
Imdelltra
tarlatamab · DLL3 x CD3Not stated in public reviews
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not stated in public reviews
Lynozyfic
linvoseltamab · BCMA x CD3Not stated in public reviews
Ordspono
odronextamab · CD20 x CD3Not stated in public reviews
Removab
catumaxomab · EpCAM x CD3Not stated in public reviews
Talvey
talquetamab · GPRC5D x CD3Not stated in public reviews