Hesperos Inc. provides insights into novel drug candidates at the preclinical stage by evaluating their efficacy and safety using sensitive, functional readouts in human-on-a-chip multiorgan models to reduce and eventually eliminate the use of animal models. This innovative new technology is helping pharmaceutical researchers, large and small, make more informed decisions on which drugs to move forward with, ultimately bringing patients new therapeutics cheaper and quicker than ever possible before and enabling patient-specific treatments.
As pharmaceutical companies aim to tackle more complex diseases, the companies are faced with higher failure rates and larger investments lost. The net result is that only 1 in 1,000 new compounds will make it to approval, most of which will fail during animal testing. Even for the ones that make it through animal models, 9 in 10 will fail during human clinical trials. One reason for high failure rates is the continued reliance on animal models, which can be poor predictors of clinical results, especially when testing therapeutics for more complex diseases.
In the early 1990s, our CEO Michel Shuler had an observation that would lead to a revolutionary idea, sparking decades of research. Animal models were poor predictors for therapeutics in humans. He envisioned a more predictive model, thinking that recent advances in engineering multicellular culture systems could be the key to designing it utilizing PBPK modeling tools. He coined these models “animal-on-a-chip”- a term that would later become organ-on-a-chip (OOC) and now human-on-a-chip.
Costly and Poor Predicators
Animal models are poor predictors of human response: 11% of drugs entering clinical trials came out as approved products.
For every 50 drugs found safe for animals, only 1 proves safe in humans (2%); One drug company finds that only 6% of animal trials predict human response
In parallel, Hesperos’ Chief Scientist, James J Hickman, was developing engineered cell culture systems utilizing serum-free medium and defined surface compositions as well as functional readouts that mimic physiological, mechanical and electrical functions such as cardiac and skeletal muscle contractions and neuronal and cardiac electrical properties. These systems are capable not only of acute measurements but long-term chronic evaluation. Hickman has also utilized stem cells to derive most neuronal cells as well as muscle and cardiomyocytes and worked these systems into multi-organ constructs. He had also developed modeling and simulation tools to predict and understand function in these systems.
About 10 years ago, Shuler and Hickman attended talks by each other and decided a collaboration to combine the unique attributes of their systems to develop multi-organ systems with functional readouts for acute and chronic applications would be revolutionary for the field. They also adapted their respectful modeling capabilities to enable Physiologically based pharmacokinetic modeling of this unique in vitro platform to enable the models to predict in vivo behavior.
Fast forward a decade and the promise of their human-on-a-chip technologies has become a reality. While these technologies are still young, they have already shown effective at predicting the effects of many therapeutics. As they gain wider acceptance in research, they are becoming more refined and the data they are generating are allowing researchers to make more informed decisions.
In 2011 The NIH established NCATS to address the long timelines, steep costs and high failure rates associated with the drug development process. To further support this initiative, in 2012 the NIH and FDA partnered to form a collaboration with the Defense Advanced Research Projects Agency (DARPA) focused on advancing development of organ-on-a-chip technology and created the Tissue Chip
Program. Shuler and Hickman were funded in the initial grant period of the initiative by NIH.
Hesperos became the first spin-off company from the NIH/DARPA program and in 2018 the company’s technology was the first to reach the Phase IIb of funding from NCATS, which is awarded to proven technologies that require additional effort to enable regulatory acceptance and cross the “valley of death” for biotechnology startups.
The future is bright for Hesperos and other OOC researchers. The applications of this technology are expanding past developing therapeutics and into the realm of personalized medicine. We are actively working to the day when this technology can be used to predict an individual’s reactions to therapeutics. Until that day, we are proud to continue to be one of the leaders for the advancement of this field.