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A new agreement for old partners
SCHLIEREN, Switzerland—InSphero AG, a Swiss supplier of assay-ready 3D cell culture models for accelerating drug discovery and development, has entered into an agreement with Pfizer Inc. to develop a novel predictive toxicology assay using InSphero 3D InSight Human Liver Microtissues. This novel test will aim to leverage the novel qualities of the InSphero 3D liver models, which may allow for the multiplexing of several endpoints to help detect and predict mechanisms of drug toxicity.
InSphero CEO and co-founder Dr. Jan Lichtenberg says, “Our 3D liver models enable researchers to better predict potential toxicity and side effects using more biologically relevant cell based assays. These models may also help reduce dependency on animal models that add significant cost, delay time to market and often fail to accurately reflect how humans will respond to a drug. We already have a long-standing relationship with Pfizer, and this new agreement will enable the development of assays with potentially even greater utility and predictive power for Pfizer’s early drug development.”
Dr. Simon Messner, who will lead the project for InSphero, adds, “The longevity and organotypic nature of 3D InSight Human Liver Microtissues highly correlates to that of native liver, exhibiting appropriate cellular organization, cytochrome P450 enzyme responsiveness and metabolic functionality. Using this 3D model could result in improved accuracy and precision by which certain DILI [drug-induced liver injury] mechanisms are predicted in vitro.”
According to InSphero, what makes the InSight microtissues unique is their ability to live in culture more than 28 days, increasing sensitivity by allowing longer drug exposure times. In addition, the liver microtissues display more in-vivo-like metabolism and transporter function. It was this longer culture time, and potential to provide greater functionality and better results compared to their existing in-house 2D model, that most appealed to Pfizer in the partnership.
“Although Pfizer has used InSphero models prior to this agreement, the study plan aims to leverage InSphero’s advanced 3D liver models to develop and potentially multiplex novel assays that are better able to predict drug-induced liver injury and also help elucidate potential mechanisms underlying DILI,” said Lichtenberg.
Using only a single viability endpoint, the InSight model offers double the sensitivity of standard primary human hepatocyte (PHH) assays for predicting known DILI compounds, without a loss in specificity, according to InSphero. The study with Pfizer seeks to explore the potential of additional endpoints (possibly in combination) to extract even greater predictive mechanistic insights from the InSphero model system.
“We are very encouraged that this agreement, along with the results of a recently completed multisite study with Genentech and AstraZeneca, is further indication that our models continue to gain the attention of pharma for their potential to help detect liver injury sooner. It also signifies confidence in InSphero to deliver standardized 3D models that are designed to meet the reproducibility and mechanistic complexity needs of pharma-scale preclinical safety testing,” Lichtenburg remarked.
The collaboration with Pfizer is the latest in a series of fruitful partnerships for InSphero. The specialized capacity of the 3D InSight Human Liver Microtissues was initially corroborated by an intensive validation study conducted by Genentech and AstraZeneca. Another recent announcement highlighted the InSphero suite of human and animal-derived liver microtissues for investigative toxicology applications, with a new test for detecting mitochondrial toxicity working in combination with the Agilent XFe96 Analyzer from Agilent Technologies. The long-term metabolic competence of 3D liver microtissues enables flexible drug exposures of up to 14 days, while the XFe96 Analyzer allows assessment of mitochondrial function through sensitive and precise measurement of cellular oxygen consumption rate on a single microtissue level.
InSphero is working on a number of additional advances to explore the capacity of their assay technologies. Says Lichtenburg, “We continue to work with other industry, regulatory and academic partners to build better cell-based assays that combine our advanced models with the latest assay technologies. We are also working towards commercializing microphysiological system (MPS, i.e., body on a chip) technology to interconnect multiple microtissues or different types of microtissues, such as liver and pancreatic islets, in a microfluidic device to increase the translational value of preclinical in-vitro testing.”