SAN DIEGO—Organovo Holdings Inc. presented five sessions at the Society of Toxicology’s (SOT) 55th Annual Meeting and ToxExpo, March 13 to 17, in New Orleans to demonstrate the broad applicability of its exVive3D Human Liver Model for the assessment of drug safety and the detection of clinically relevant modes of liver injury, including steatosis and fibrosis.
Organovo, which is “a marriage of engineering and biology,” uses 3D bioprinting technology to develop three-dimensional human tissues aimed at “delivering scientific and medical breakthroughs,” according to Paul Gallant, general manager. The result is better models for preclinical testing, he said, adding that “There is a need in drug discovery for preclinical models that translate into the human condition better than rodents.”
“Current methods of preclinical using in-vitro assays in a test tube or in-vivo assays with animals fall short,” he explains. “Using complex human tissue, we can do experiments we were never able to do before.”
Organovo, which began in 2007 with technology licensed from the University of Missouri, has compiled validation data over the past year to research compounds known to be toxic and drugs that are toxic to the liver. According to Gallant, “No in-vitro models could have detected this data. This is the only tissue model where researchers can induce fibrotic disease and detect disease and toxicity by using human tissues.”
The exVive3D Human Liver Model is created by taking primary cells, putting them into bio ink and putting them on a 3D printer in spatially controlled matter. As Gallant explains, “For instance, the liver has three different cell types. We build a physical piece of tissue and measure metabolic, genomic and biochemical endpoints.”
The model “provides an accurate, predictive and reproducible model of human liver biology for preclinical toxicity testing,” Gallant adds. At the SOT Annual Meeting, Organovo and some of its pharmaceutical customers—including Bristol-Myers Squibb and Astellas—highlighted recent results that showed how the 3D bioprinted human liver tissue “effectively models in-vivo tissue composition and physiology.” The company currently offers the liver model as a service to customers including four of the top 25 global pharmaceutical companies, but hopes to deliver it as a product, Gallant comments.
According to Dr. Sharon Presnell, Organovo’s chief technology officer and executive vice president of research and development, “Drug-induced liver injury remains a major cause of late-stage clinical failures and market withdrawal, often due to poor translation from preclinical animal studies to clinical outcomes. Organovo’s exVive3D human liver model replicates complex cell-cell interactions and key elements of native tissue architecture to enable the detection of multiple clinically relevant modes of tissue injury, including necrosis, immune-mediated tissue damage, steatosis and fibrosis. When a preclinical or clinical-stage asset presents a challenging safety or efficacy signal, exVive3D provides the unique resolving power of a controlled human tissue microenvironment to investigate mechanism and develop solutions.”
Organovo’s 3D human tissues have the potential to accelerate the drug discovery process, enabling treatments to be developed faster and at lower cost, according to Gallant. The exVive3D platform technology portfolio began with the recent launch of the exVive3D Human Liver Tissue for use in toxicology and other preclinical drug testing. Additional products are in the pipeline, with the anticipated release of the exVive3D Human Kidney Tissue scheduled for the third quarter of 2016.