The Environmental Protection Agency kicked off its ToxCast program by awarding $111 million in contracts to eight biopharmaceutical companies this month. The contracts, which range from $4 million to $69 million, are part of an initiative that will use drug discovery technologies to predict the toxicity of environmental chemicals.

Initiated last year by the EPA's National Center for Computational Toxicology (NCCT), ToxCast seeks to maximize the limited resources with which the EPA must evaluate thousands of environmental chemicals. The program will use pharmaceutical industry approaches such as high-throughput screening, toxicogenomics and computational chemistry to create a database of toxicity information that would help the EPA prioritize the chemicals that present the greatest threat to human and environmental health and speed evaluation of new chemicals.

The largest contract went to NovaScreen Biosciences, a division of Caliper Life Sciences Inc. Over two to five years, the Hopkinton, Mass-based company stands to get at least $1.4 million and up to $69 million, depending on the volume of testing required and the availability of EPA funds in future years.

David Manyak, executive vice president of discovery services, said Caliper will use its 750 assays "covering virtually every target class" to evaluate the pesticides and environmental chemicals. Manyak also heads up Caliper's Discovery Alliances and Services (CDAS) business unit, launched in January to integrate the in vitro discovery services of NovaScreen, acquired in late 2005, with the in vivo expertise of Xenogen, acquired in mid-2006. (See BioWorld Today, Sept. 9, 2005, and Feb. 14, 2006.)

Caliper's biochemical and cellular assays already have been validated in the pharmaceutical industry, where the company has between 200 and 250 partners. Pfizer Inc. is the most recent addition to the roster: Caliper announced on Monday a one-year contract with the big pharma to provide in vivo profiling services aimed at elucidating new uses for existing compounds.

Another ToxCast contract recipient was Cellumen Inc., of Pittsburgh, which may get up to $5.5 million over a two- to five-year period. Rather than utilizing high-throughput screening, however, Cellumen will take a systems biology approach.

Cellumen has created a "very data rich" panel of cells based on hepatotoxicity that "looks at systemic response," according to President and CEO D. Lansing Taylor. The Cellumen cytotoxicity profiling method measures 11 cellular systems biology parameters for a 10-point dose-response at three time points: one hour to represent acute settings, 24 hours to represent early settings and 72 hours to represent chronic settings. The company then uses informatics tools to analyze the 330 data points generated per compound and provide insights into mechanism of action.

As with Caliper, Cellumen's technology was developed for use in drug discovery and development. Taylor said the company will have an announcement soon about a theragnostics platform for better stratification of patients in clinical trials. Cellumen is also in the process of raising a Series B financing.

Other companies receiving contracts include BioSeek Inc., of Burlingame, Calif., for up to $12.8 million; Expression Analysis Inc., of Durham, N.C., for up to $5.8 million; In Vitro ADMET Laboratories LLC, of Rockville, M.D., for up to $5.7 million; Phylonix Pharmaceuticals Inc., of Cambridge, Mass., for up to $4.3 million; Attagene Inc., of Morrisville, N.C., for up to $4 million; and ACEA Bioscience Inc., of San Diego, for up to $4 million.

The companies receiving contracts will begin by screening a set of approximately 200 well-known chemicals from different structural classes that cause varying phenotypic outcomes such as tumorgenesis, reproductive toxicity and neurotoxicity. Once the technologies pass that validation test, they may be used to screen up to 10,000 chemicals including drinking water contaminants, antimicrobials and pesticidal ingredients. The resulting data could be mined for relationships between the various structural domains of the chemicals and known toxicological properties, providing the base for a model that predicts toxicity.

The NCCT also entered into a five-year agreement with the National Institutes of Health National Chemical Genomics Center to profile nearly 1,500 environmental chemicals. The work will be conducted both internally and with external vendors, and results will be made public through the National Library of Medicine's PubChem database.

The public availability of those findings could benefit the pharmaceutical industry by associating certain chemical structures with toxicity, potentially helping drug developers to be "more efficient and accurate in determining toxicology earlier," Manyak said.