Florida-based Hesperos is changing the paradigm of clinical development with its organ-on-a-chip technology and new research that demonstrates the platform can predict in vivo response to medications and reduce the need for animal testing.
Collaborative research with AstraZeneca published in the journal Nature Scientific Reports were able to use the technology to evaluate the pharmacokinetics and pharmacodynamics of an antihistamine that has long been discontinued due to toxicity concerns. Additionally, Hesperos analyzed a small molecule from AstraZeneca’s library and confirmed its toxicity in heart and liver models. The company’s multi-organ model was able to successfully measure the concentration and metabolism of two known cardiotoxic small molecules over time. The technology allowed the researchers to accurately describe the drug behavior and toxic effects in vivo. James Hickman, Hesperos’ chief scientist, told BioSpace in an exclusive interview, that the data from the study has the potential to revolutionize the drug discovery process.
“We really believe we can change for the better how the drug discovery process works,” Hickman said.
Hesperos was founded by Michael Schuler, a professor emeritus at Cornell University who is known as the father of the organ-on-a-chip technology. Schuler, who has more than 25 years of experience in the field, secured the first patents for the technology.
For the collaboration with AstraZeneca, Hesperos used a pumpless heart model and a heart/liver system to evaluate the pharmacokinetic and pharmacodynamic (PKPD) relationship for terfenadine, an antihistamine that was banned due to toxic cardiac effects. Additionally, the technology was able to determine its mechanism of toxicity, which Hickman said had never really been understood. Data from the study revealed there was a time-dependent, drug-induced response in the heart model, he said. The research continued with the addition of a metabolically competent liver module to see what happened when terfenadine was converted to fexofenadine, an antihistamine such as Allegra. By doing this, Hickman said Hesperos was able to determine the driver of the pharmacodynamic effect and then predict the effect of terfenadine in preclinical species. Hickman said this study was the first time an in vitro human-on-a-chip system has been shown to predict in vivo outcomes. The data is important because it can be used to predict clinical trial outcomes in the future, he said.
In addition to the antihistamine, Hesperos tested a failed AstraZeneca small molecule that was known to have cardiovascular risks. The molecule was assessed for hERG inhibition. The researchers concluded it had a low potential to cause in vivo QT prolongation. The QT interval approximates the time from when the cardiac ventricles contract to when they finish relaxing. Prolongation of the QT interval on the electrocardiogram can lead to a fatal arrhythmia. When Hesperos tested the molecule, it was able to detect a clear pharmacodynamic effect at concentrations of 3 μM and worked to determine the mechanism of toxicity of the molecule.
Not only could the success of the organ-on-a-chip platform reduce the reliance on animal subjects in preclinical work, the technology could reduce the costs drug companies spend on trials. However, Hickman noted that it typically takes time for companies, particularly larger ones, to change the course of operations. He likened that change to the slow maneuverability of many ocean liners – a few degrees at a time.
In addition to the potential cost reduction of the Hesperos technology, another advantage of the organ-on-a-chip technology is it will be able to provide doctors and pharmacists with a greater understanding of how certain drugs will interact with others. In noting that many older people can take a number of different medications for a wide range of medical issues. Hickman said the Hesperos technology can be used to show whether or not adding a new drug into a patient’s regimen could have toxic effects.
Based in Orlando, Hesperos was the first company spun out from the Tissue Chip Program at National Center for Advancing Translational Sciences (NCATS). The company is funded through NCATS’ Small Business Innovation Research program. In August, the company will move from its current in an incubator location near the University of Central Florida campus to a new 14,000 square foot facility.
“We are busting at the seams,” Hickman said.
In addition to its work with AstraZeneca, Hesperos has also conducted work with Roche, Sanofi and several smaller biotechs. Looking ahead at the remainder of the year, Hickman said the company is looking at adapting an immune system component into its technology. Hickman said this will be one of “the next big scientific things” the company does. Also, Hickman said Hesperos will also continue to use its technology to support client research programs. Between his and Schuler’s combined experience in the field, Hickman said there isn’t much the due has not seen, so they have a good idea of what is and isn’t feasible for their clients.
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