Unloxcyt
cosibelimab
Species
Monkey
Longest study
13 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Cynomolgus monkey only
“the cynomolgus monkey (Macaca fascicularis) was the only pharmacologically relevant animal species for the assessment of pharmacokinetics (PK) and toxicology.”
Why that species
Binds monkey and human PD-L1 with high affinity; no binding to murine PD-L1
“cosibelimab selectively binds to monkey and human PD-L1 with high affinities, but not to murine PD-L1.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys
“One non-Good Laboratory Practice (GLP) PK study and 2 GLP toxicology studies (4- and 13-weeks, including TK) were conducted with cosibelimab in cynomolgus monkeys (Table 44).”
Study lengthopen answer page →
Longest pivotal study
13 weeks
“Slow bolus intravenous injection via a saphenous vein once weekly for 13 weeks (14 doses) at a dose volume of 2 mL/kg.”
Pivotal GLP studies
GLP 4-week and 13-week repeat-dose studies in cynomolgus monkeys, once-weekly IV slow bolus, 10-week recovery for 13-week study
“CK-301: Once Weekly Intravenous Slow Bolus Injection Toxicity and Toxicokinetic Study in Cynomolgus Monkeys for 13 Weeks with a 10-Week Recovery Phase”
Route in tox
Intravenous (slow bolus)
“Species/Strain: Macaca fascicularis Method of Administration: Intravenous Bolus Injection”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1)); large molecule not expected to interact with DNA
“Consistent with ICH S6(R1) guidance, no genotoxicity studies were conducted with cosibelimab as its large molecular weight prevents it from entering the cytoplasm/nucleus of cells and subsequently interacting with deoxyribonucleic acid (DNA).”
Carcinogenicity
Not conducted (ICH S9); no carcinogenicity risk assessment
“Per ICH S9, no carcinogenicity study or carcinogenicity risk assessment was performed.”
Reproductive & developmental
No developmental or reproductive toxicity studies; literature-based risk assessment instead
“A literature-based risk assessment of developmental and reproductive risk was conducted in lieu of performing developmental and reproductive toxicology studies.”
Safety pharmacology
Incorporated into monkey toxicology studies; no safety concerns identified
“No potential safety concerns were identified for safety pharmacology endpoints incorporated into the toxicology studies.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Unloxcyt don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for monoclonal antibodies
ADCs with cytotoxic payloads follow the S9 rules (1/10 STD10 or 1/6 HNSTD of the ADC, scaled by body surface area). For immune agonists, a MABEL-based start dose should be considered instead.
“For example, for cytotoxic payloads, the starting clinical dose can be determined using either 1/10th the Severely Toxic Dose (STD) in 10% of animals (STD10) in rodents or 1/6th the Highest Non- Severely Toxic Dose (HNSTD) in non-rodents, for the ADC based on body surface area, depending on which is the most appropriate and/or sensitive species.”
This product's starting point
NOAEL / key findings: NOAEL 100 mg/kg once weekly (highest dose) in 13-week monkey study (FDA multi-discipline review, p. 55)
NOAEL / key findings
NOAEL 100 mg/kg once weekly (highest dose) in 13-week monkey study
“No-Observed-Adverse-Effect-Level: 100 mg/kg, once per week”
Risksopen answer page →
Immune & cytokine safety
ADA in 10-50% of monkeys during dosing or recovery, incidence decreasing with dose
“In monkeys that received cosibelimab, 10% to 50% of animals were confirmed positive for the presence of ADAs during the dosing or recovery phase, with the incidence tending to decrease with increasing dose.”
Biodistribution & persistence
Mean monkey half-life 439 hours at 100 mg/kg/dose (Day 92)
“The mean half-life value was 439 hours following administration of the 100 mg/kg/dose on Day 92.”
Modality-specific risk
PD-L1/PD-1 blockade: enhanced inflammatory responses and increased severity of infections
“In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses.”