J&J Collaboration Explores Technology With Potential To Revolutionize Drug Development
By Trisha Gladd, Editor, Life Science Connect
The process of bringing a drug to market is an expensive and lengthy one. For those that are ultimately approved and commercialized, the investment is certainly worth it. Unfortunately, only about 10 percent of drugs that make it to Phase 1 clinical trials actually make it to market. If the method used to determine whether or not a protein is a viable target for drug development were improved, pharmaceutical companies could potentially avoid the losses associated with finding out too late that a drug has harmful side effects and/or a lack efficacy. So how can pharma do this? Well, fortunately for them, some new technologies are now available to enhance their ability to select and evaluate safer targets in improved cell systems.
Earlier this year, the London Design Museum awarded the Wyss Institute for Biologically Inspired Engineering at Harvard University for its Human Organs-on-Chips technology. Designed by Donald Ingber and Dan Dongeum Huh, organs-on-chips are microchips that mimic a normal human environment and could one day become a qualified alternative to animal testing in some cases. As explained on Wyss Institute’s site, “each individual organ-on-chip is composed of a clear flexible polymer about the size of a computer memory stick that contains hollow microfluidic channels lined by living human cells. Because the microdevices are translucent, they provide a window into the inner workings of human organs.”
In July 2014, the first for-profit company, Emulate, was spun off of the Wyss Institute, in order to pursue the commercialization of organs-on-chips. Almost a year later, in June 2015, a strategic collaboration was announced between Janssen Biotech and Emulate to deploy the technology in some Janssen programs. The goal of this partnership, which was facilitated by the Johnson & Johnson Innovation Center in Boston, is to be able to better predict how certain drug candidates will respond in humans as well as to improve the overall drug development process.
“One of the challenges in the pharmaceutical company is that we’re under a lot of pressure to develop new, better drugs that are safe,” explains Peggy Guzzie-Peck, global head of Investigative Safety Sciences in the Janssen pharmaceutical division at Johnson & Johnson (J&J). “We have to figure out ways of doing that better, in order to be able to keep the drugs in development, in development without them failing due to a lack of efficacy or a lack of safety. Starting by allowing scientists to better characterize the signals that they can expect in a normal human environment, organs-on-chips then lets them see how the responses change as potential new drugs are taken up by cells and alter normal human physiology. Scientists can then, in turn, make better decisions for a program.”
A Crystal Ball For Human Response
Before a drug goes into clinical trials, scientists must ensure that any human who receives it will not experience any adverse effects. For this reason, pre-clinical testing must be done under the best conditions possible. Currently, the overall effects of a drug on a living organism are studied in isolated in vitro systems or in standardized animal models before going into human clinical trials. These in vitro studies are usually conducted with single-cell types grown in static conditions. Cultures are in suspension or attached to plates under conditions that are not physiologically normal and where the culture media is changed every few days. The advantage the Wyss Institute’s technology and other new models that use organ-on-chip technologies has over these current testing conditions is that multiple cell types can be grown on a chip, in ratios that are similar to what is found in normal organs. The normal human physiology can then be mimicked in the different organs-on-chips by constantly replenishing media using flow-through technologies. This system also allows scientists to continuously monitor the actual affects a drug could have on a human organ using normal cells or those from patients with a given disease.
The organs-on-chips technology wouldn’t just be an alternative to traditional testing; it could also provide some benefits that would span across the entire drug development lifecycle. “The utility could start with the pharmacologists that use in vitro and in vivo testing to ensure the drugs are interacting with the right cell types and targets to determine if the new drugs are going to be potentially efficacious,” explains Dr. Guzzie-Peck. “Those looking at drug metabolism could use these enhanced models to look at how the drug is taken up and transported through cell membranes and how the drug is metabolized. They can also study the response of the cells by simulating different metabolic conditions by dialing up or down various enzyme conditions to change a metabolic profile. In parallel, pharmaceutical science groups making the drugs could use these systems to optimize drug delivery by testing the drug prepared in different formulations to study the uptake and transport of the drug. There is potential everywhere.” She adds that, while it is early and there is still work to be done, it’s key that pharma industry has some enhanced physiologically relevant types of platforms for screening that, hopefully, in the future will also allow them to be used in a higher throughput fashion.
A Look Ahead
J&J is working with Emulate right now on models where they can put some drugs into the system to see how they’re responding, and Dr. Guzzie-Peck says she has high hopes about the relationship. “There will always be a lot of challenges any time you’re developing a new condition. That’s part of science,” she explains. “But we’re working through most of them right now, and we’re now on a positive path forward.” Presently, the Emulate team and J&J are working on a Thrombosis-on-chip, which evolved from the original “organ,” Lung-on-chip. “The thrombosis model will allow us to study the potential for blood clot formation in critical organs such as the lung,” continues Dr. Guzzie-Peck. “We are also partnering on rat and dog liver chips that will give us the ability to see how an adverse effect seen in an animal species will translate to humans, which may allow us to reduce the future need for animals in drug development.” Eventually, the Emulate team intends to, as explained on the Wyss Institute site, “build 10 different human organs-on-chips and link them together on an automated instrument to mimic whole-body physiology.”
Continued progress is expected to be made as Emulate develops the systems further and J&J evaluates what value organs-on-chips could bring as well as what limitations the technology could face. Overall, the future is bright. “The thing that has been impeding us for years was the technical limitations of our culture systems and using transformed cell lines that are just not normal,” explains Dr. Guzzie-Peck. “Now, with advanced engineering technology and through the development of systems that are microphysiologially enhanced, which allows them to better simulate human physiological conditions, this has enabled us to culture human primary cells in induced pluripotent stem cells from normal and diseased patients for several weeks in culture. With organs-on-chips, we could potentially use these types of systems for employing more innovative and human-relevant ways, as one more tool that will further enable us to bring safer and more efficacious drugs to patients faster.”