Enjaymo
sutimlimab
Species
Monkey
Longest study
26 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 was the only nonclinical species demonstrated to be pharmacologically relevant, and the nonclinical program was conducted only in that species.”
Why that species
Comparable binding to monkey and human C1s (EC50 0.13 vs 0.15 nM) and similar hemolysis inhibition; no binding/inhibition in mouse, rat, rabbit, minipig, dog
“Sutimlimab binds cynomolgus monkey and human C1s with comparable affinity (EC50, 0.13 nM and 0.15 nM, respectively)”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys
“The cynomolgus monkey was the only nonclinical species demonstrated to be pharmacologically relevant, and the nonclinical program was conducted only in that species.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“A 26-week toxicity study was conducted in cynomolgus monkeys intravenously administered sutimlimab at 60 and 180 mg/kg/week.”
Pivotal GLP studies
Cynomolgus monkey 5-week (up to 100 mg/kg/week) and 26-week (up to 180 mg/kg/week) IV studies with 8-week recovery
“Sutimlimab has been evaluated in repeat-dose studies in cynomolgus monkey for 5 (up to 100 mg/kg/week) and 26 weeks (up to 180 mg/kg/week) with 8 weeks of recovery.”
Route in tox
Intravenous (once weekly)
“The intravenous route of administration was utilized in the repeated toxicology studies and the enhanced pre and postnatal study to match the intended clinical administration route.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (monoclonal antibody, ICH S6)
“No genotoxicity studies were performed with sutimlimab, as monoclonal antibodies are generally considered devoid of mutagenic or clastogenic risk.”
Carcinogenicity
Not conducted; weight-of-evidence (no proliferative lesions in chronic monkey study, mechanism, literature): no significant tumorigenic potential; ECAC concurred
“Given the absence of proliferative lesions observed at either dose tested in the chronic monkey study and the lack of any identified tumorigenic risk based on the mechanism of action and a search of the relevant scientific literature, it is unlikely that sutimlimab possesses significant tumorigenic potential.”
Reproductive & developmental
Monkey ePPND up to 180 mg/kg/week (~4x clinical exposure): no adverse reproductive or developmental effects; no dedicated fertility study
“There were no adverse effects on reproductive or developmental outcomes at 180 mg/kg/week, which represents 4 times the human exposure at the 7.5 g clinical dose.”
Safety pharmacology
Incorporated into repeat-dose monkey study; no adverse cardiovascular, respiratory or CNS effects
“Safety pharmacology endpoints incorporated into the repeat-dose toxicology study in monkeys did not identify any sutimlimab-related adverse effects on cardiovascular, respiratory or central nervous system endpoints at either dose.”
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 Enjaymo 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 outside oncology
Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.
“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”
This product's starting point
NOAEL / key findings: NOAEL 180 mg/kg/week (highest dose) in repeat-dose monkey study; no adverse findings despite near-complete classical complement inhibition (FDA pharmacology/toxicology review, p. 40)
NOAEL / key findings
NOAEL 180 mg/kg/week (highest dose) in repeat-dose monkey study; no adverse findings despite near-complete classical complement inhibition
“The no observed adverse effect level (NOAEL) in the repeat-dose toxicity study was 180 mg/kg weekly in male and female monkeys.”
Risksopen answer page →
Immune & cytokine safety
Minimally immunogenic: ADA in 2/10 animals at 60 and 1/10 at 180 mg/kg/week, increased clearance, no immune complex disease
“in 2/10 animals at 60 mg/kg/week and 1/10 animal at 180 mg/kg/week. However, while sutimlimab clearance was increased in these animals, no adverse impacts on the health of animals (e.g., immune complex deposition) were observed.”
Biodistribution & persistence
Human TCR: expected staining consistent with complement proteins, no unintended cross-reactivity; no tissue distribution or placental transfer studies
“Sutimlimab showed an expected staining pattern in human tissue line with other complement proteins. There was no obvious cross-reactivity staining to un-intended target(s).”
Modality-specific risk
Infection risk (especially encapsulated bacteria) from classical complement pathway inhibition; no infection signal in animals
“The classical complement pathway is an important defense against infections, especially encapsulated bacteria, but no signal for increased infections was observed in nonclinical studies.”
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