Which animal species did regulators accept for approved bispecifics?

“The cynomolgus monkey was utilized as the only pharmacologically relevant species for toxicity testing, in view of cross reactivity of MCLA-128 with the HER2/HER3 targets in this species.”

“Together, these results support the use of cynomolgus monkeys as the pharmacologically relevant species for zenocutuzumab toxicity assessment.”

“General toxicology studies included non-terminal repeat-dose studies of intravenous administration of blinatumomab in chimpanzees and repeat-dose studies of subcutaneous and intravenous administration of a murine surrogate in mice.”

“Blinatumomab bound to B and T lymphocytes from human and chimpanzee peripheral blood mononuclear cells (PBMC) but it did not bind to PBMC from the mouse, rat, beagle dog, squirrel monkey, African Green monkey, cynomolgus monkey, rhesus monkey, and baboon.”

“The cynomolgus monkey is a relevant species for toxicology studies based on glofitamab binding to CD20 and CD3 on cynomolgus monkey B- and T-cells.”

“Glofitamab bound to human and monkey B-cells with EC50 values of 4.3 and 2.3 nM respectively and bound to human and monkey T-cells with EC50 values of 21.1 and 13.2 nM respectively. This justified use of the cynomolgus monkey for general toxicology studies.”

“Cynomolgus monkey was identified as the only relevant nonclinical toxicology species based on elranatamab binding affinities for BCMA and CD3.”

“Selection of cynomolgus as relevant species appears adequate, based on comparable binding affinity of elranatamab to cynomolgus and human BCMA and CD3, and a comparable frequency and phenotype of cynomolgus and human BCMA+ cells.”

“The nonclinical toxicity profile of epcoritamab was established in a series of nonclinical safety studies in cynomolgus monkeys, the only cross-reactive toxicology species.”

“The epcoritamab binding data indicates that among the species tested, the cynomolgus monkey is the only pharmacologically relevant species for toxicology studies.”

“Emicizumab was shown to bind similarly to the corresponding cynomolgus monkey coagulation factors, as such the cynomolgus monkey is a pharmacologically relevant species.”

“In an enzyme assay using purified Cynomolgus monkey, rat and mouse FIXa and FX, emicizumab was found to cross-react only with the corresponding clotting factors of Cynomolgus monkeys.”

“The cynomolgus monkey was selected for toxicology testing given that tarlatamab similarly bound human and monkey CD3 and DLL3 but did not bind CD3 from other species.”

“However, the monkey may not be pharmacologically relevant considering DLL3 is expressed intracellularly in normal cells and tissues.”

“There are no pharmacologically relevant animal species to evaluate tebentafusp toxicity.”

“In vitro, the scFv portion of tebentafusp bound to T cells in human PBMCs but did not bind PBMCs from mouse or monkey.”

“None of the animal species analysed is suitable for assessing the safety of catumaxomab.”

“None of the studies demonstrated binding of catumaxomab to cells from non-clinical species.”

“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.”

“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.”

“Overall, data indicate that linvoseltamab bound human and Cynomolgus monkey BCMA, but not rat or mouse BCMA.”

“Overall, data indicate that linvoseltamab bound human and Cynomolgus monkey BCMA, but not rat or mouse BCMA.”

“Binding to human and cynomolgus CD20 and CD3 was confirmed in in vitro studies. Cynomolgus monkey was considered the pharmacological relevant species further used in toxicology studies.”

“An additional binding study showed that odronextamab did not bind to either B-cells or T-cells isolated from mouse and rat.”

“A number of common laboratory animal species, including the three monkeys marmoset (Callitrix sp.), cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) were tested histologically for catumaxomab binding, but none showed a binding pattern similar to that of human tissues, and were consequently considered non-relevant.”

“The non-clinical programme was adapted to the fact that catumaxomab is a protein, and its binding properties are essentially specific for humans.”

“The cynomolgus monkey was selected as the only pharmacologically relevant species for the nonclinical pharmacokinetic (PK) and toxicology assessments of amivantamab based on a comparison of sequence homology, cross-species comparisons of relative target-binding affinities, and functional activity in cell-based assays.”

“Amivantamab bound to the ECD of human and cynomolgus monkey EGFR and MET with similar EC50 values (Table 3), but not to the ECD of rat EGFR or MET (data not included in review).”

“Toxicology studies were not conducted in rodents due to the lack of talquetamab or JNJ-64024701 cross reactivity in these species.”

“Due to the lack of cross reactivity of talquetamab to cynomolgus monkey GPRC5D, the tool molecule (JNJ-64024701) was developed.”

“The cynomolgus monkey was selected as the only pharmacologically relevant species for the nonclinical PK and toxicology assessments of teclistamab based on cross-species comparisons of sequence homology, relative target-binding affinities, and functional activity in cell-based assays.”

“The parental CD3 monoclonal antibody did not bind rodent CD3, and teclistamab is not expected to bind rabbit CD3 or BCMA due to low sequence similarity; thus, the cynomolgus monkey was determined to be a pharmacologically relevant species for toxicology studies.”

“She agreed, as the Applicant proposed, that the monkey alone should be used in the planned 6-month chronic toxicity study.”

“The monkey was selected as the most relevant species based on 100% sequence homology (VEGF) and binding affinity (Ang-2) comparable to humans.”

“The toxicology program was carried out in cynomolgus monkeys, as it was demonstrated that the cynomolgus monkey and human have relevant HER2 sequence homology and affinity.”

“It was demonstrated that zanidatamab binds with similar affinity to human and cynomolgus monkey HER2 ECD (Kd = 0.74 and 0.47 nM, respectively), while the affinity for dog was lower (Kd = 4.07 nM) and no affinity was demonstrated for rodents”