Aucatzyl
obecabtagene autoleucel
Species
no relevantMouse
Longest study
2 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No relevant species; no in vivo tox. NSG xenograft (pharmacology) and human tissue cross-reactivity only
“Per the applicant, conventional nonclinical toxicology studies were not conducted because they do not yield clinically relevant information for a CAR T cell product.”
Why that species
No pharmacologically responsive species; human autologous T cells will not engraft in immunocompetent animals; immunodeficient models uninformative
“Aucatzyl, a patient-specific product, is not appropriate for administration to immunocompetent animals, as the T cells will not engraft.”
Surrogate molecule
No surrogate; nonclinical CAT19 CAR T cells from healthy-donor PBMCs with identical construct judged representative
“Despite minor differences between the nonclinical and clinical products, the constructs assessed, including the binding domain, were identical and therefore the nonclinical product is considered appropriate to assess safety and activity in the nonclinical program.”
Study lengthopen answer page →
Longest pivotal study
2 weeks
“CAR T cells were present in peripheral blood as well as bone marrow two weeks post-injection.”
Pivotal GLP studies
No in vivo GLP tox; GLP human tissue cross-reactivity (42 tissues); non-GLP NALM-6 NSG xenograft, single IV dose, Day 16
“The GLP tissue cross-reactivity study was conducted to determine potential binding of 1 or 3 μg/mL CAT19 to 42 normal human tissues and blood smears.”
Route in tox
Intravenous (xenograft pharmacology study only)
“Route of Administration Intravenous (IV)”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (third-generation SIN lentiviral vector, release criterion, long-term clinical monitoring for insertional mutagenesis)
“No nonclinical genotoxicity studies were conducted with obe-cel based on the genotoxic risks associated with the third-generation self-inactivating lentiviral vector used to produce obe-cel, acceptable release criterion, and inclusion of long-term clinical monitoring for insertional mutagenesis and clonality.”
Carcinogenicity
Not conducted (ICH S9; no murine CD19 cross-reactivity; murine T cells resist LV transformation)
“Carcinogenicity studies are not needed for indications falling under ICH S9 scope (advanced cancer). In addition, there is no cross-reactivity of the CD19-CAR T cells from Aucatzyl with the murine antigen.”
Reproductive & developmental
Not conducted (ICH S9; no pharmacologically relevant species)
“DART studies are not needed for indications falling under ICH S9 scope (advanced cancer) and no pharmacologically relevant animal species is available.”
Safety pharmacology
Not conducted; human-specific product with immune-related risks, immunocompromised models of limited relevance
“No safety pharmacology studies with obe-cel were conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL (no tox studies); tissue cross-reactivity limited to CD19+ B cells in lymphoid tissues, no off-target binding
“The data indicate that human tissue cross reactivity with the CAT19 CAR binding domain was consistent with the expected profile of CD19 expression on B lymphocytes.”
Risksopen answer page →
Immune & cytokine safety
No nonclinical CRS/ICANS model; CRS and neurotoxicity judged clinically manageable; CAT19 showed higher TNF-α in vitro/in vivo
“Known risks of CAR T cell therapies (e.g., CRS or neurotoxicity) can be clinically monitored and managed.”
Biodistribution & persistence
No dedicated PK/biodistribution; CAR T cells in blood and bone marrow at Day 16 in NSG mice; persistence assessed clinically
“Traditional non-clinical pharmacokinetic studies (absorption, distribution, metabolism, excretion and in vitro drug-drug interaction) have not been conducted because obe-cel is an autologous gene therapy product and there is no pharmacologically relevant species.”
Modality-specific risk
LV insertional mutagenesis/secondary malignancy (literature-based assessment), bystander transduction, follicular DC on-target off-tumor depletion
“However, it is also explained that the risk of transformation and oncogenesis with the current third generation SIN LVs and moderately active non-viral promoters is low (but not zero), especially in terminally differentiated cell types such as T cells.”