There is a significant unmet need for human models for risk assessment that can be utilized for drug optimization in early development. Clinical safety failures are only predicted by nonclinical studies 25% of the time because of (1) lack of predictable in vitro models; (2) rodents show low concordance (42%) with human clinical outcomes; and, (3) non-human primates are more predictive, but limited by cost, throughput, and ethics.
Historically, cell cytotoxicity assays are conducted using model cell lines that that are useful for characterizing non-specific drug toxicities at high doses. Intestinal off-target effects are the most common adverse events in Phase I clinical trials and often reflect biology specific to the GI tract, which are not represented in common cell lines.
Altis’ RepliGut® Planar model is a unique in vitro model of the intestinal epithelium, which provides a critical barrier against luminal pathogens and is essential for efficient nutrient absorption. A damaged gut epithelium can lead to rampant negative systemic effects, so understanding the toxicity of compounds is essential prior to in vivo trials. The RepliGut® Planar model provides a physiologically-relevant, primary-cell derived intestinal epithelial monolayer that can be used to investigate cell health through a variety of established read-outs, including assays focused on barrier function, cytokine secretion, and gene and protein expression.
RepliGut® tissue constructs have the potential to address critical needs in pharmaceutical drug development. Based on human intestinal stem cells, RepliGut® eliminates the issues associated with the use of immortalized cells lines, such as Caco-2. The polarized monolayers express tight junction proteins and recapitulate the barrier function of the intestine in vivo. Additionally, RepliGut® monolayers express all of the major cell lineages found in the intestinal epithelium. Because RepliGut® uses healthy, normal (not cancerous) human primary cells, they provide more physiologically relevant results. Intestinal stem cells used for the RepliGut® system are harvested from transplant-grade human donor tissue for which there is no recipient match. As such, the stem cells are very high-quality with extremely low necrotic or ischemic damage.
The form factor for the platform is an SBS format multiwell plate with Transwell® inserts, and the platform can be used in 12 or 96-well plate formats, so it is high-throughput and easily integrated into standard laboratory equipment and workflows. Luminal and basal reservoirs allow compounds and additional cell types to interact with the epithelial cells for side-specific assays.
With this design, RepliGut® can more accurately model different behaviors in the intestine, such as the barrier function. Altis’ goal is to reduce the time and cost of drug development, as well as reduce the need for animal testing.
To introduce this patented, cutting-edge technology Altis will offer one company/researcher a research project (value up to $10k). Open to all organizations, commercial and academic.
If the submitted project cost is over $10k a credit will be applied to a comprehensive program.
Types of Programs
Toxicology (Risk Assessment, Safety, Drug Discovery)
Permeability Assays, Transepithelial Electrical Resistance (TEER), Gene Expression, Protein Expression, High Content imaging, Immunohistochemistry
RepliGut® is a unique, human stem cell-derived platform that recreates the intestinal epithelium in a continuous monolayer of stem and differentiated cells. RepliGut® can be purchased as a product, or Altis Biosystems can provide the services you require.
The high throughput platform supports quick screening of many candidates and fosters efficient development through reduced timelines and costs. Focus applications include preclinical studies for compound screening, investigating the effects of diseases, and microbiome research.
Drug safety/toxicology; the treatment effects on stem cell proliferation and differentiation.
- Opening Date: July 27,2022
- Submission Due Date: October 3,2022
- Review Dates: October 3 - December 5, 2022
- Award Date: December 9, 2022
- Project Start Date: Approximately January 9, 2023
About the Sponsor
Altis Biosystems is a biotechnology company that has developed a patented stem cell platform which recreates the human intestinal epithelium in a high-throughput format for drug screening and microbiome research. Stem cells are sourced from transplant-grade donor intestine. Altis provides a variety of contract research services for customers and sells the platform as a kit. Services include Inflammation, Barrier Function, Toxicology, and Drug Disposition. Our goal is to reduce the time and cost of drug development with a platform that more accurately reflects native human biology and reduce the need for animal testing.
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