ONCOLOGY

Cancer is the 2nd leading of cause of death globally*. It is also the first therapeutic area in terms of investigated drugs in preclinical phase and clinical trials.

Preclinical research in oncology needs to answer several pharmacological considerations such as on- and off-target effects, pharmacokinetics and pharmacodynamics (PK/PD), maximum tolerated dose, efficacy in relevant models and the therapeutic window (the balance of efficacy and toxicity),

Non-human primates are often considered a relevant species to test large molecules and immunotherapies as they share greater similarity in regard to their genetic evolution, immune system, physiology and metabolism as well as the expression of target molecules.

This predictive model is well suited for lead optimization, de-risking clinical adverse effects such as immunotoxicity or CRS, and exploration of dose-response relationships in toxicology.

* source: WHO 2018

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Efficacy studies
No efficacy models currently available for the moment.
Exploratory studies
  • Pharmacokinetics
  • Central Pharmacokinetics
  • Pharmacodynamics
  • Early toxicology studies
  • Delayed-Type Hypersensitivity (DTH) model
  • Immunopharmacology model (TDAR)

Pharmacokinetics

Pharmacokinetics

  • Circulating drug kinetics following most routes of administration (more information)
  • Cutting-edge expertise for in vivo central pharmacokinetics 
    • Blood sampling
    • Cerebrospinal fluid (CSF) drug levels
    • Brain microdialysis to monitor neurotransmitters, drugs or metabolites in the extracellular cerebral fluid.
      Discover our proprietary platform Kine C3

Clinical follow-up and Bioanalysis

  • Daily clinical monitoring for the early detection of adverse effects
  • Monitoring of physiological parameters and other biomarkers of interest
  • Bioanalysis (more information)

Central Pharmacokinetics

With the rise in drugs targeting various neurodegenerative diseases, it becomes crucial to assess the actual bioavailability of these products at the expected region of interest, that is, the Central Nervous System.

Cynbiose developed an expertise in the in vivo and ex vivo assessment of CNS drug bioavailability in a relevant preclinical model the non-human primate.

Objectives

  • Assess the relative bioavailability of a product in the CNS (CSF, local extracellular fluid, whole brain) compared to the plasmatic concentration
  • Characterize proteins or genes of interest in endothelial or epithelial cells of the NHP blood-brain barrier
  • Assess the crossing of the Blood-brain barrier (BBB) for drugs targeting tumors of the Central Nervous System (CNS)

 

Methods

  • Classic or intrathecal ROA
  • Repeated sampling of CSF and plasma in non-human primate
  • Microdialysis in specific part of the brain in awake NHP
  • Characterization of NHP brain microvessels or choroid plexus by proteomic, transcriptomic or in-situ hybridization

Readouts

  • PK measurements in whole organs, plasma, CSF, brain dialysate
  • Cytokines measurement in various medium

 

 

 

Type of drugs

  • Small molecules
  • Biologics
  • Immunotherapies targeting the CNS
  • Oligonucleotides, ASO
  • Peptides
  • Viral vector

Scientific publications

  • Thiollier, T., Wu, C., Porras, G., Bezard, E., Li, Q., Zhang, J., & Contamin, H. (2018). Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics. Animal Models and Experimental Medicine, 1(4), 314–321. DOI
  • Thiollier, T., Wu, C., Contamin, H., Li, Q., Zhang, J., & Bezard, E. (2016). Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease. Synapse, 70(6), 231–239. DOI

 Scientific partners

  • Motac Neurosciences: Motac provides highly – specialised preclinical research services to pharmaceutical and biotechnology companies that are developing new treatments for neurological diseases, particularly neurodegenerative conditions like Parkinson’s disease or other motor and cognitive disorders.

Pharmacodynamics

More information here.

Early toxicology studies

Type of studies

  • Single and repeated doses, dose escalating studies
  • Immunosafety, immunogenicity
  • Pulmonary tox and respiratory function
  • Dose Range Finding (DRF)
  • Maximum Tolerated Dose (MTD)

Type of test item

  • Immunotherapies
  • Antibodies, ADC, …
  • Cell therapies, gene therapies, oncolytic virus
  • Oligonucleotides, antisense oligonucleotides
  • Therapeutic vaccines such as DNA vaccines, RNA vaccines
  • Recombinant proteins, recombinant enzymes
  • Peptides
  • Oncolytic viruses (BSL2 biocontainment, GMO C2)
  • Small molecules, ….

non-exhaustive list

 

Delayed-Type Hypersensitivity (DTH) model

Immunopharmacology model

 

Delayed-type hypersensitivity (DTH) is a low invasive model based on the induction of local cellular immune responses.

This NHP model is reliable for the preclinical evaluation of cell-mediated immunity of biological drugs and non clinical immunotoxicity evaluation.

 

Model

  • Species: Cynomolgus macaque (Macaca fascicularis)
  • Model induced by KLH, Tetanus-based vaccine (TTx), BCG

Type of test item

  • Immunosuppressive agents
  • Immunomodulatory drugs
  • Vaccines / adjuvants

Efficacy read-outs

  • Clinical reactions at the injection sites (proprietary scoring grid)
  • Clinical pathology
  • Cutaneous reaction : morphological readouts, histopathology, immunohistochemistry
  • Immunomonitoring
  • On-demand and customized readouts

 

Scientific publications

  • Développement préclinique des immunothérapies : apport des modèles PNH. Verset M, Mosca M, Panzuti P, Contamin H, Pin D. STAL. 2018, 46(2): 12-16.
  • Preclinical development of immunotherapies for infectious diseases: relevance of the Non-Human Primate. Verset M, Contamin H. I4ID congress, 2017, 11-12 Dec. 2017, Lyon.
  • Développement préclinique des immunothérapies : apport des modèles PNH. Verset M et al. 43ème colloque AFSTAL, 7-9 Juin 2017, Lyon.

 

 

 

Immunopharmacology model (TDAR)

 

Immunopharmacology model: T cell dependent antibody response (TDAR) (Tetanic toxoid, KLH)