▼ Abstract （クリックで非表示）

Compounds in development are rarely, if ever, tested in vitro using complex biological systems that capture the relationships of hierarchical networks involving multiple molecular targets, pathways, cells and tissues. Consequently, the impact of a compound on the complex and integrated signaling networks is largely undefined prior to clinical studies. Emerging novel therapeutic approaches such as immune-checkpoint antibodies, epigenetic modulators and rationally designed combinations highlights the need for better, clinically validated in vitro human disease models to support early identification, characterization, optimization and clinical translation of new therapies.

The BioMAP platform is an in vitro phenotypic profiling service that screens agents in human primary cell-based systems that represent the physiology of cells and tissues found in a complex disease states. All BioMAP systems are constructed with one or more human primary cell types pooled from healthy donors, and stimulated with cytokines, growth factors and other molecules to capture relevant signaling networks that occur in human tissue or disease biology. Each test agent generates a signature BioMAP profile that is created from the changes in protein biomarker readouts within individual system environments. Biomarker readouts are selected for therapeutic and biological relevance, are predictive for disease outcomes or specific drug effects and are validated using agents with known mechanisms of action (MoA). Using custom-designed software containing data mining tools, a test agent's BioMAP profile can be compared against a proprietary reference database of > 4,000 BioMAP profiles of bioactive agents (biologics, approved drugs, chemicals and experimental agents) to identify the most similar profiles or to benchmark against competitor agents. This robust data platform allows rapid evaluation and interpretation of BioMAP profiles by performing the unbiased mathematical identification of common or differentiating activities. Specific BioMAP biomarker activities have been correlated to in vivo biology and multiparameter BioMAP profiles have been used to distinguish compounds based on MoA and target selectivity. BioMAP profiling provides a predictive signature for in vivo outcomes across diverse physiological systems that informs on MoA, target selectivity, biomarkers for efficacy and safety, dosing and indication selection.

Incorporating knowledge from more than a decade of experience in phenotypic profiling using human primary cells, a suite of BioMAP services can be used to evaluate the impact of a test agent in the context of complex disease relevant biology. The 12 human primary cell-based systems in the Diversity PLUS™ panel model broad human tissue and disease biology that includes the vasculature, skin, lung and inflammatory tissues. Quantitative measurements of biomarker activities, along with comparative analysis against bioactive agents in the BioMAP Reference Database can inform on the safety, efficacy and function of a test agent. Additionally, the Tox Alert Analysis service identifies mechanism-based Toxicity Signatures that consist of 2 - 5 biomarker activities associated with adverse clinical outcomes. The platform also includes multiple diseased focused panels that facilitate in vitro characterization of test agents for clinical efficacy in the context of (i) the immune suppressed tumor-microenvironment (TME) in oncology (CRC and NSCLC panels), (ii) the adaptive immune responses in auto-immune diseases (T Cell Autoimmune panel) and (iii) the inflammatory and fibrotic processes that drive fibrosis (Fibrosis panel). Additionally, our Combo ELECT service in any nominated system provides an evidence based approach to prioritize agents for combinations by determining if, and how, a combination represents an enhanced therapy.The BioMAP Phenotypic Platform thus presents a useful approach to (1) provide actionable information on compounds with respect to efficacy and safety impact on human tissue and disease biology (2) identify activities of these agents as predictive biomarkers of clinical response and (3) prioritize agents and qualify combination strategies. Together, these BioMAP data will support the discovery, characterization, optimization and development of safer and more effective therapies in autoimmunity, fibrosis, oncology, immuno-oncology, and other human diseases.

▼ Abstract （クリックで非表示）

Axol Bioscience Ltd (Axol) is a world renowned, biotechnology company, with an expertise in creating human induced pluripotent stem cells (iPSC). The foundation of Axol, is its iPSC-derived neural cell range, which provide well characterised and physiologically relevant tools, which are being used to model neuronal behaviour and understand disease mechanisms. Axol has expanded its product range by developing other novel iPSC-derived cell types, such as cardiomyocytes, renal cell and macrophages, as well as broadening its portfolio with a range of primary cells, ensuring that Axol meets its vision of being a supplier of human cells and associated reagents and media.

The first section of this presentation will focus on the disease modelling capability of Axol's neuronal cells and will give academic case studies to further understand the application of these neuronal cells in disease models. The second section will focus on Axol's human iPSC-derived cardiomyocytes and human iPSC-Derived Renal Proximal Tubular Cells for use in toxicology studies.

All the cells in Axol's iPSC-derived neuroscience range are highly characterised and ideally placed for studying neurodegenerative conditions including Alzheimer's disease, frontotemporal dementia and Parkinson's disease.

The use of iPSC-derived cardiomyocytes as an in vitro research model provides a major advantage over primary cells and they provide a continuous source of cardiomyocytes from the same genetic background for use in multiple experiments. Our human cardiomyocytes are ideal for use in cardiotoxicity testing and we will present a simple and scalable platform for cardiotoxicity screening assays.

The human iPSC-Derived Renal Proximal Tubular Cells express markers of renal proximal tubule cells such as GGT and CD13 and transporters OAT1, OAT3, OCT2 and PEPT1 to comparable levels to primary human renal proximal tubule epithelial cells.

The presentation will show that we have identified a range of characteristics in the neuronal, cardiomyocyte and renal proximal tubular cells that establishes them as an ideal tool for use in numerous applications such as disease modelling, drug screening, toxicology and other assays.

▼ Abstract （クリックで非表示）

The high rate of attrition among clinical-stage therapies underscores the need for in vitro testing models that more accurately recapitulate in vivo human biology. Human tissue biology is strongly influenced by the unique inter play and extensive cross talk that exists between different resident cell populations. These cell types are most often spatially arranged in a specific architecture which defines their biological function and mechanistic response to drug treatment over time. However, most conventional in vitro cell-based systems used to test candidate drugs lack these key biological features. Three-dimen sional bioprinted tissues are able to successfully model this cellular complexity and therefore offer major advantages over conventional in vitro systems with respect to predictive modeling. Bioprinted tissues incorporate key architectural features and primary cell types which can be maintained in culture on a timescale of several days to weeks.

The primary goal of this session will be to educate participants on the bioprinting process and how this technology is currently being applied in the manufacture of several types of human tissues. Specific case studies will highlight the advantages of using bioprinted tissue to study aspects of liver and kidney disease and drug-induced toxicity.