Solutions to address challenges in the assessment of drug efficacy

1. Various phenotypic methods using human cells (disease models)

Axcelead prepares a variety of human cells (disease models), using various cell lines and hiPS cell-derived differentiated cells, and conducts various phenotypic analyses in order to select or prioritize oligonucleotide drug candidates for our clients.
An original cell assay system that is suited to your objectives can be constructed upon consultation by taking advantage of our experience in screening and compound assessment techniques.

2. Assessment of drug efficacy using animal disease models

The efficacy (PD/drug efficacy) of drug candidates for animal disease models with high clinical extrapolation capability is assessed and data for a clinical trial are provided.
A study design with minimal requirements is proposed, and drug efficacy is assessed upon consultation, utilizing our extensive experience in drug discovery.

[Examples of drug efficacy assessments using animal disease models conducted by our company]
“Assessment of ACC inhibitor efficacy using a mouse disease model for nonalcoholic steatohepatitis (NASH)”

-Etiology: Lifestyle-related diseases
-Pathology: Fatty liver and liver fibrosis
-Animal disease model: MC4 receptor-deficient mice fed a high-fat diet
-PD: Malonyl CoA in the liver
-Drug efficacy: Inhibition of fatty liver and liver fibrosis
navigate_next Article on the assessment of drug efficacy using MC4R KO mice (PLOS ONE website)

3. Generation of genetically-modified mice and rats

Using genome-editing technology (CRISPR/Cas9 system), genetically-modified mice and rats, with a targeted gene deleted or mutation inserted, can be efficiently generated and provided.
Axcelead can replace a human gene, which is targeted by oligonucleotide drugs, with a mouse gene, while maintaining the exon/intron structure.
We can also provide a number of genetically-modified mice required for a trial within a short period of time (gene-deficient F0 mice can be provided within 3 months) using in vitro fertilization technology, allowing you to quickly begin your desired trial.

【Examples of animal disease models provided for oligonucleotide drug discovery】
『Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5』
 Nature Communications  volume 11, Article number: 2777 (2020)
navigate_next Results of an in vivo study carried out by Axcelead and published in Nature Communications.