Encelto
revakinagene taroretcel
Species
RatDogRabbitPig
Longest study
26 wk
Genotox
Conducted Conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Minipig, pig and rabbit (ocular tox/PK); rcd1 dog for pharmacology; rat and rabbit for rhCNTF DART
“The effect of long-term ITV implantation of NT-501 was evaluated in a 3-part toxicology study in 4–8-month-old minipigs, 4–10-year-old pigs”
Why that species
Disease-relevant animal models support CNTF photoreceptor protection; no explicit species rationale for tox species
“Histopathologic studies in naturally occurring and genetically engineered animal models of photoreceptor dysfunction that phenotypically model retinitis pigmentosa support a role for rhCNTF”
Surrogate molecule
No surrogate cell product; representative NT-501 device used; DART used recombinant human CNTF SC in rat/rabbit
“The nonclinical development program evaluated a product representative of ENCELTO”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“There was no evidence of systemic exposure to rhCNTF after ITV implantation of NT-501 in minipigs for up to 6 months or in rabbits for up to 9 months.”
Pivotal GLP studies
Non-GLP 12-week rabbit ocular tox/PK; 3-part minipig/pig long-term ITV implant study to 6 months; unencapsulated-cell device failure study in minipigs
“The effect of long-term ITV implantation of NT-501 was evaluated in a 3-part toxicology study”
Route in tox
Intravitreal (ITV) implantation via pars plana sclerotomy; SC rhCNTF in DART studies
“ENCELTO is intended for surgical implantation by intravitreal (ITV) insertion via a pars plana sclerotomy.”
Skipped studiesopen answer page →
Genotoxicity
Done: ISO-10993 battery (bacterial, mammalian cell, mouse micronucleus on device extracts), negative
“No genotoxicity was observed in these studies.”
Carcinogenicity
Not conducted (waived based on toxicological risk assessments)
“Studies to evaluate the carcinogenicity/tumorigenicity of ENCELTO were not conducted.”
Reproductive & developmental
Four DART studies of SC rhCNTF in rats and rabbits; no teratogenicity; exemption for device via margin of exposure
“There were no rhCNTF-related teratologic changes reported in the fetuses.”
Safety pharmacology
Not stated as separate studies; ERG assessments for intraocular implants in pharmacology
“Electroretinographic (ERG) Assessments for Intra-Ocular Implantation of”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL set for device; minimal lens, vitreous and ocular inflammation; no systemic findings. rhCNTF DART NOAELs used for margins of exposure
“ITV implantation of NT-501 did not cause any effects on systemic clinical signs, gross pathology, or histopathology of non-ocular organs.”
Risksopen answer page →
Immune & cytokine safety
Minipig/pig studies to 6 months showed no immune response to rhCNTF or cells; mild to moderate ocular inflammation
“Two preclinical studies in minipigs or pigs implanted with NT-501-6A.02 device for up to 6 months showed no immune response to rhCNTF or cell producing the protein.”
Biodistribution & persistence
No systemic rhCNTF exposure after ITV implant (minipig to 6 months, rabbit to 9 months); implants delivered about 7-9 ng/day
“In rabbits, NT-501 implants established CNTF levels averaging about 7-9 ng/day for up to 9 months.”
Modality-specific risk
Local ocular toxicity from capsule/rhCNTF dose (cone effects at high output), device failure with cell release, systemic CNTF exposure
“a dose-response to rhCNTF was present, with eyes implanted with empty capsules and capsules with a low CNTF output cell line exhibiting less intense changes than eyes implanted with NT-501.”
Similar precedents
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