Caliper Life Sciences has been awarded $2.9 million under the EPA's ToxCast screening program to evaluate 700 environmental compounds. Separately, the agency reports that it will also assess over 100 drugs provided by Pfizer, GlaxoSmithKline, sanofi-aventis, and Merck & Co. with its ToxCast screening tool.
These drugs were nixed early in clinical development because of their toxicity profiles. EPA researchers will screen the drugs and compare their results with the clinical trial data.
The long-term goal of EPA's ToxCast program is to identify in vitro assays that can predict the toxicity of chemical compounds in humans and animals. Initially, results of in vitro testing conducted by Caliper and others will be compared with toxicity data from EPA's in vivo toxicity database, ToxRefDB. The resulting predictive tests will be used to supplement or replace existing animal-based tests, reduce cost, and improve the speed of regulatory approval of new environmental chemicals, EPA predicts.
Task orders have generated approximately $5.3 million in total revenues for Caliper since the initiation of the contract in April 2007. In Phase I Caliper tested 320 well-known chemicals in more than 230 in vitro assays. Phase II kicked off in November 2009 with $1.8 million from the EPA, and now an additional $2.9 million has been awarded. The contract is being carried out by the Caliper Discovery Alliances and Services (CDAS) unit.
“Phase II of the ToxCast program will involve screening another 700 environmental compounds through a wide set of assays,” says David Manyak, evp, drug discovery services. “We expect to begin the Phase II effort within the next several months after the Phase II compound library is delivered to us by the EPA.”
The initial phase of the EPA ToxCast program was aimed at creating a database of in vitro assay data on a broad set of compounds for which in vivo safety data already existed. Key goals were to assess overall data quality and establish that the database was predictive of in vivo toxicity profiles.
Preliminary analyses of the data generated at CDAS from the first phase indicate that the goals for high-quality data and potential predictive power have been met, the company notes. For the 11 replicate controls included in the initial 320 compound set, there was greater than 99% concordance in the screening results across 240 assays tested. More than 200 correlations between the in vitro results generated at CDAS and in vivo toxicity parameters have already been identified. In addition, 75% of the assays tested showed activity for one or more compounds, reinforcing the need for broad in vitro profiling.
The Phase II task orders involve screening the 700 new compounds against a panel of 81 G-protein coupled receptor (GPCR) assays, which is a subset of Caliper’s current ToxCast assay panel of 275 assays in total, explains Manyak. “The EPA expanded Caliper’s original Phase I ToxCast panel of 235 assays in the third quarter with the addition of 40 new kinase and other enzyme assays. All of these new assays are performed on Caliper’s LabChip EZ Reader® instrument, which reflects the high quality of data obtained with our LabChip systems.
EPA’s contract with Caliper under the ToxCast program provides for up to $69 million of screening services over five years. The specific dollar value is subject to the actual volume of testing requested by the EPA as well as continued government funding for the ToxCast program.