Humanizing the Drug Discovery Process

CAMBRIDGE, MA—The emerging practice of testing new medicines on miniature samples of human tissue, known as organ-on-a-chip, is facing a major challenge: single organs can’t replicate the body’s multi-organ environment. Drug toxicity, and often efficacy, can be a consequence of a series of events involving several organs. Failure to account for these interactions, or crosstalk, between organs deprives the drug development pipeline of potentially safe and effective therapies and contributes to the high failure rate in drug trials.

“The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for drugs at the preclinical stage,” said Jeffrey T. Borenstein, a Bio Systems and Tissue Engineer at Draper and co-author of a peer-reviewed paper published in Lab on a Chip. The paper describes Draper’s success in proving the effectiveness of the company’s biomimetic platform for testing.

Borenstein added: “What is needed in clinical drug development is a test platform that creates a microenvironment similar to the environment within the body where you can precisely control drugs, nutrients and metabolites in organ models that mimic the human body. Particularly challenging is a system that can test multiple interconnected organs for disease models or safety science, which we have demonstrated in this paper.”

Pharmaceutical companies can use Draper’s Human Organ System (HOS) platform to test new drugs, yield more accurate results earlier and more cost-effectively in drug trials, make drug development safer and identify drugs that are false negatives in animal models. The platform technology developed at Draper offers a precise, robust and reliable approach that enables crosstalk between multiple organ models.

Draper’s predictive model of 3-D human tissues approach uses constructs of organ tissues within a microfluidic system that is representative of the environment within the body. By developing a device that contains living human cells capable of recapitulating organ-level functions, Draper aims to provide better translational preclinical models for efficacy and safety evaluation of drugs, biologics and nanotherapeutics.

Draper’s HOS platform can test a candidate therapy on multiple organ tissue types, said Jonathan R. Coppeta, lead author of the Lab on a Chip publication. Draper’s microfluidic pumping technology enables the HOS platform to mimic the circulation of metabolized drugs from one organ type to another, sequenced according to how that drug would be processed by organs in the human body.

“We have engineered an environment that encourages cells to function in vitro as they would in specific human organs in vivo,” Coppeta said. “Scaling these systems into a multiplexed architecture for individual or multiple organ models for diseases and toxicological studies will provide a significant benefit to the drug development process.”

In the paper, researchers demonstrate organ-to-organ interaction between liver and airway tissue models. This cell-to-cell signaling, or crosstalk, helps to overcome one of the challenges of drug discovery, which is translation of predictions from in vitro to in vivo and from preclinical to clinical.

Single Organ Test Platform

Draper is developing several drug development platforms for the commercial market. The company recently announced a three-year agreement with Pfizer Inc. (NYSE: PFE) under which the companies will collaborate to create customized versions of Draper’s PREDICT96 system for Pfizer. 

PREDICT96 is a multiplexed (or high throughput) predictive single organ test platform. PREDICT96 contains wells, seeded with cells of human tissues relevant to the drug to be tested and the disease to be treated; Draper has modeled liver, kidney and other organs and is actively modeling more. Draper also is developing disease models for various human organs.