Preclinical PK analysis

4 steps you need to follow for successful PK assessment of your compound

Relying on wild-type mice or inappropriate humanized models may result in a potentially viable drug candidate being rejected, or important adverse drug reactions not being detected, as occurred in the TeGenero 2006 clinical trial with TGN1412. This can happen when drug safety experiments are performed in PBMC-reconstituted mouse models that do not consider the contribution of myeloid cells to the elicited immune response and which contain a majority of pre-activated T cells.

We have developed a wide range of translational pre-clinical models to meet your research needs, which can be used alone or in complementary ways to maximize and accelerate your research. They are either readily available for purchase (see our Catalog Models) or can be developed specifically for you (see our Customized Models).

Our selection of catalog models includes different types of models useful for safety assessment.

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Target-specific humanized models

A wide range of target-specific humanized strains is available and ready for purchase. These models are immunocompetent, and display a physiological expression of the human target. Some of the models present in our catalog include:

The humanized SA and FcRn model (genO-hSA/hFcRn) has been validated by many companies, such as argenx and Crescendo Biologics, and is available for the assessment of therapeutics with extended half-life via FcRn recycling and/or HSA binding. We also have available models such as the genO‑panhCD3/hSA/hFcRn that enable the PK testing of T-cell engagers with an increased half-life.

The humanized TFRC model (hCD71), was validated by Lundbeck and allows you to test the PK and biodistribution of constructs aiming to cross the blood-brain barrier, or of therapies targeting CD71-overexpressing cancers, as demonstrated by Bratti et al., 2024. Additionally, we have developed a new genO‑hTFRC/hSA/hFcRn mouse model for improved biodistribution and drug shuttling of HSA- or hFcRn-binding compounds.
Our humanized FcγR and FcRn model is a powerful tool for PK assessment of Fc-competent therapeutic antibodies (AACR 2024 poster).
Several humanized immune checkpoint models, such as the genO-hVISTA and the genO-hCD47/hSIRPα models, among many others. With these models you can assess the PK of your human-specific immunomodulators/immunotherapies, as demonstrated by Sensei Bio with a new hVISTA-targeting antibody (Thisted et al., 2024), or for biodistribution analysis to help understand treatment response and enable patient stratification (Wagner et al., 2023).

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Cell lines

Another important consideration when performing PK tests for cancer drugs is whether the tumor might impact the drug’s pharmacokinetics. Therefore, if you would like to analyze the PK of your drug in a cancer biology context, our humanized mouse models can be used for syngeneic studies, for which there is available a complementary catalog of cell lines.

A variety of cell lines are available, such as colon carcinoma cells lines (MC38 and CT26, for C57BL/6 and BALB/c mice, respectively) or a lymphoma cell line (EL4).
These cell lines are engineered to express human proteins such as CD19 or CD20 (in the EL4 background), or humanized immune checkpoints (in MC38 and CT26 backgrounds).
We also provide a range of reporter and Knockout cell lines, which can be used as a control for your efficacy studies and target validation.

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Immunodeficient models

In our vast portfolio, you can also find immunodeficient rodents. These models can be used for PK and biodistribution assessment in very specific cases too. These include analyzing the pharmacokinetic and biodistribution profiles of a drug without the potential of inducing anti-drug antibodies (ADA). Additionally, our immunodeficient models support PDX and CDX engraftment, which also enables the PK and biodistribution assessment in the context of cancer, as well as allow longer experimental timeframes due to their extended longevity.