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NHP Immuno-Safety

De-risk clinical trials with early toxicity screening of I/O agents

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"CrownBio brings clarity to drug discovery around the world by helping biopharmaceutical companies solve some of today's most pressing problems in oncology, cardiovascular, and metabolic disease.

Leveraging our industry expertise, CrownBio's global resources help customers answer the most challenging questions about human biology. We begin with the end insight to help you achieve your goals"

Dr Jean-Pierre Wery
CEO, Crown Bioscience Inc.

Non-GLP Exploratory Toxicology Studies in NHPs

Evaluate the physiological effects and safety of your immunotherapies with our comprehensive non-GLP NHP platform. Our models provide you with quick, cost-effective, and robust data to guide future GLP work and clinical trials.

NHPs are the only clinically-relevant model for assessing immune-related toxicity, allowing preclinical evaluation of potentially fatal clinical toxicities e.g. cytokine storm. NHPs have a high homology to humans, fully intact immune system, and cross-reactivity to antibodies which are not recapitulated in rodents or other larger animal models.

Advantages of our Non-GLP NHP Platform

  • Save time and simplify logistics with I/O NHP toxicology and murine studies run at the same facility. Seamlessly move from mouse I/O work to NHP toxicology

  • Reduce development time and improve cost effectiveness with onsite pathology/histopathology services, including IHC, ICC, and IF

  • Rapid study initiation for fast turnaround of robust results - studies can be started within 4 weeks (dependent on test article availability), with study duration optimized to fit client and project needs

  • Cost-effective pathway to guide your GLP studies – our exploratory non-GLP toxicology screen typically runs at a fraction of the cost of a GLP study

Comprehensive Non-GLP Analysis

Assess the immuno-safety of a range of I/O agents including mAbs, CAR-T cell therapies, ADCs, vaccines, small molecules, cytokines, and oncolytic viruses using:

  • Healthy immunocompetent cynomolgus macaques
  • A range of common administration routes
    • Intravenous injection or infusion
    • Intramuscular injection
    • Subcutaneous injection
    • Oral routes – via diet or gavage
  • Perform FACS and immunoprofiling of common immune cell markers including cytokines, CD markers, immune checkpoint targets with fast turnaround on additional marker validation
  • Analyze serum markers using industry gold standards: Beckman Coulter AU480 clinical chemistry analyzer, Luminex, MesoScale Discovery single and multi-plex systems
  • Perform clinical observations to identify potential adverse effects related to cytokine storm/CRS
    • Changes in heart rate and/or body temperature
    • Facial redness or swelling
    • Vomiting, diarrhea, tremor, lethargy, low blood pressure, difficulty breathing

Figure 1: Representative NHP FACS profiling data

Figure 2: Representative cytokine and chemokine PLEX data

Marker
Immune Cell Population
CD45 Total leukocytes
CD3 Total T cells
CD4 CD4+ T helper cells
CD8 CD8+ Cytotoxic T cells
CD44/CD62L Naive, memory and effector T cells
CD69/CD44/OX40/CD25 etc Activation markers
CD4+CD25+FoxP3+ Regulatory T cells
CD11b+IA/IElow/- G-MDSC and M-MDSC
Ly6c/Ly6g Macrophages
CD11b+ F4/80 M1 and M2 Macrophages
IA/IE/CD11c/CD206 NK cells
CD3-CD335+ NKT cells
CD3-CD335+ B cells
CD19 Cytokines
TNF-a/IFN-r/IL-7/IL-3 etc Checkpoint inhibitors
Granzyme B etc Commonly requested markers
KI67/Brd U/PNCA et Proliferation
Live/Dead (fixable) Live/Dead
CD45 Total leukocytes
CD3 Total T cells

Table 1: Target panel for NHP profiling