Cellumen this week announced the launch of a new CellCiphr panel that is designed to predict cardiac hypertrophy as early as possible in the drug-discovery process, and represents the first CellCiphr panel that includes cardiac cells.
A Cellumen official told Cell-Based Assay News this week that currently pharmaceutical companies see approximately a 90-percent failure rate among their drug candidates. “Too many compounds that are destined to fail go further [than they should] in the drug discovery and development process,” said Cellumen CEO Lansing Taylor.
“In the past 10 years, nearly 30 percent of all drugs in the United States have been withdrawn due to cardiotoxicity,” Kate Johnston, Cellumen’s chief scientific officer and vice president of discovery programs, said in a statement released as part of the launch announcement.
In theory, by identifying as early as possible those drug candidates that are destined to fail due to cardiotoxicity, drug companies can save millions of dollars in development costs.
The new rat cardiomyocte cell-based panel is based on the H9c2 cell line, and is designed to simultaneously measure eight distinct toxicity indicators in candidate compounds including mitochondrial function, oxidative stress, apoptosis, and cellular hypertrophy.
Cellumen intends the launch to help it accomplish both a short- and a long-term goal. “The driving force of what we are doing is in two stages,” Taylor said. The first goal is to offer clients as quickly as possible a more powerful and predictive tool for in vitro safety testing.
That would be done using rodent cell panels, because some companies want to use better in vitro tools earlier in the drug-discovery process to better predict what compounds should not go forward without further review into additional preclinical rodent studies, said Taylor.
In parallel, some pharmaceutical companies and European safety unions also want to completely replace animal testing. “So we are also developing corresponding panels of human cells” for cardiotoxicity testing, Taylor said.
Taylor said that Cellumen has signed an undisclosed pharmaceutical company as its first customer for the cell line panel.
Cellumen has, in the past, worked with the US Environmental Protection Agency, the Food and Drug Administration, Mitsubishi Tanabe, Eli Lilly, and Roche.
Taylor said that the company plans to launch the panel of human cardiomyocytes in 2009.
“[T]oo many compounds that are destined to fail go further in the drug discovery and development process.”
“We believe that the future of this is to build a whole set of panels to represent major organ systems.” The company plans to develop panels that represent other major organs, including the kidney, the brain, and the immune system, to predict the toxicity of drug candidates on these systems.
“Ultimately, our vision is that if there is a chance, and we believe that there is, to minimize and, perhaps at some later date, replace animal testing, it will involve panels of human cell-based systems, with a classifier wrapped around those panels, Taylor said. “That is where we are going.”
The reality is that, in the near term, meaning within the next five years, the industry “just needs better tools to make better decisions on prioritizing lead series” — in Taylor’s words, what goes down the pipeline into preclinical testing, and to get a handle on the mechanism of action if toxicity is detected.
However, “the FDA, for example, is not going to stop doing animal testing within, say, the next five years,” Taylor said. “What we assume will happen is that the FDA will begin to require parallel data on in vitro and in vivo models, and the data will prove itself.” He said that is a “five-year-plus process.”
In the meantime, pharmaceutical companies have compounds in the pipeline, and they have to generate preclinical data, while decreasing the development cycle time and expense. So right now, Taylor said, they want to know “‘What are the things that should be red flagged from a lead series?’ So in the worst case scenario, the medicinal chemists can say, ‘This has some potential problems — let’s go back and take a closer look.’”
For discovery toxicology, both for outsourcing applications and supplying tools to the companies, the annual global market is over $500 billion and growing at double digits, said Taylor.
“I think it's very interesting” that Cellumen is getting into predicting cardiotoxicity, Casey Laris, director of applications for Vala Sciences, which markets cell-image-based reagents and analysis software tools, told CBA News via e-mail this week. “We completely agree that cardiotoxicity can and should play a much larger role earlier in the drug-discovery process.”
He added that accurately predicting cardiotoxicity is an “obvious opportunity” to reduce the total cost of bringing a new drug to market. “If — as most sources agree — it costs around $1 billion to bring a new drug to market, and about 80 percent of that cost is in the clinic, truly knowing the cardiotoxicity behavior of these candidates early in the process is of paramount importance.”
At the American Society for Cell Biology’s 48th Annual Meeting, held this week in San Francisco, Vala presented work describing a new hypertrophic index it developed for cardiotoxic analyses.
“We've extended this first order hypertrophic measurement with a more extensive tool for quantifying the organization of the myofibril contractile apparatus,” Laris explained.
This work corroborates with Vala’s larger stem-cell strategy. For instance, the company last week won a $900,000 grant from the California Institute for Regenerative Medicine to refine cardiomyocyte stem cell differentiation and production techniques.
The company is also involved in an ongoing project in collaboration with the Burnham Institute to develop a device called the calcium transient imaging cytometer that automates the measurement of calcium transient kinetics on cardiac cells in a high-throughput imaging mode.