Axiogenesis AG is the leading Biotech Company providing human induced pluripotent stem cell (iPSC)-derived cell types for high-throughput screening in early drug discovery and toxicology. When Axiogenesis was founded in 2001, the drug industry was suffering from costly late-stage drug attrition, due to the employment of animal models and cell lines with uncertain biological relevance and reproducibility.
A prominent reason for late-stage drug attrition is drug-related cardiovascular complications. Initially Axiogenesis focused on the development of mouse stem cell-derived cardiomyocytes and developed high predictivity assays for drug safety and drug efficacy. By 2010 Axiogenesis had launched stem cell derived cardiomyocytes (Cor.At®), smooth muscle cells (Smac.4M®) and endothelial cells (Endo.4M®) produced by its proprietary production technology enabling 100% pure cell populations.
Human iPSC-derived cell types
When the nobel prize winning iPS cell technology from Yamanaka became available in 2007, Axiogenesis was the first european company to licence and adopt this technology in 2010. In 2012 Axiogenesis launched Cor.4U® human iPSC derived cardiomyocytes, and all assays previously developed for Cor.At® cells were transferred to employ human iPSC derived cardiomyoctyes. In 2014 Axiogenesis launched the first two neuronal subtypes: human peripheral (Peri.4UTM) and human dopaminergic (Dopa.4UTM) neurons, as well as in vitro differentiated electro-competent cardiac fibroblasts (Fibro.4UTM).
All cell types of the Axiogenesis portfolio are 100% pure, extremely well characterized and show a typical morphology, protein expression, electrophysiology and pharmacology of primary cells. Assays were developed and validated on numerous platforms, also in collaboration with device manufacturers to give proof of the applicability of Cor.4U® and the other cell types on low throughput to high throughput systems (table 1). The latter enabling the use of Axiogenesis cells on various formats up to 1536 well plates, important for HTS in early drug discovery. Manual Patch Clamp, Automated Patch Clamp, MEAs, calcium transient measurements and impedance-based assays is also available in-house for custom assay development and to guarantee high quality applications, protocols and scientific support. Besides Axiogenesis is the only Biotech Company that additionally accommodates cell drums, an application to directly analyse cell force and tension.
Cardiac Hypertrophy Disease Model
The hypertrophic cardiomyopathy (HCM) assay, addresses one of the most frequent and cost intensive diseases these days. This genetic heart muscle disease occurres in 1 out of 500 people and is the most common cause for heart-related sudden death in people under 30. Cardiac hypertrophy is a disease with high unmet need, where the only treatment available is heart transplantation or merely the mitigation of symptoms.
Axiogenesis developed cardiac disease models using human iPSC-derived cardiomyocytes, where the diseased phenotype is induced either via chemical stimulation or via the use of genetic variants to create the same phenotype as the disease in vivo.
The higher predictivity of phenotypic screening in combination with physiologically relevant human cells is turning target based drug discovery upside down. Or rather it is turning drug discovery the right way up again; starting with the disease and the reversion of the disease and only then identifying the target and MOA.
The HCM disease model is suitable for HTS, enable direct screening of compounds reverting the diseased phenotype. This allows the direct identification of a novel drug candidate. siRNA screen will yield novel and valuable targets.
This disease model filled the gap of a suitable cell-based assay with physiological relevance and Axiogenesis was early to apply for patent protection (in 2004) and received patent protection in USA, Europe and Japan between 2011-2012. These patents include any stem cell derived cardiomyoctyes used as a disease model regardless of the method of induction of the disease phenotype or the readout.
A key goal of Axiogenesis in the near future is the customisation of neuronal and cardiac cells for drug development through the introduction of targeted mutations and reporter genes via gene editing (e.g. CRISPR/Cas9). This customisation will produce several novel disease models in cardiac, neuronal and hepatic cell types as well as reporter genes for specific HTS targets.
In collaboration with the US Food and Drug Administration (FDA) under the Health and Environmental Science Institute (HESI) CiPA initiative, Axiogenesis is working to establish iPSC-derived cardiomyocytes as a recommended test system for cardiac safety.
Located at the Cologne Biocampus, one of the biggest biotechnology parks in Germany, the 27 employees of Axiogenesis can take advantage of the existing infrastructure, the ideal geographical position and the nearby companies of the Life-Science industry to increase and strengthen customer relations in Europe.
A company base and cell production facility in the USA is currently in development, and sales representatives located in the US, the UK and Italy support the Axiogenesis brand to maintain the reputation as an indispensible provider of hiPSC-derived cell types for drug industry and academia. Never losing the focus on desired cell types by industry, Axiogenesis R&D works on the development of new products to steadily increase the portfolio.