It took about 20 years for Oxford Biomedical Research to find proteomics, but the company that started out as a protein-purification firm now has its eyes on getting a slice of the $1.1 billion pie for in vivo toxicology preclinical pharmaceutical testing.
Oxford, based in Rochester Hills, Mich., was recently selected to participate in the 2007-2008 National Institutes of Health Small Business Innovation Research Commercialization Assistance Program to help commercialize the company’s toxicoproteomics technology, called ToxProfiler.
Denis Callewaert, president and CEO of Oxford, acknowledges the platform is several steps away from commercialization, and only two weeks ago met with the company’s CAP adviser for the first time to explore ways of getting it to market. Ultimately, the goal is to develop ToxProfiler as sandwich immunoassays composed of organ-specific protein biomarkers to identify and monitor diseases.
The ToxProfiler and the ProteoMine protein-depletion technology are at the forefront of Oxford’s efforts carve out a spot in the proteomics universe. ProteoMine version 1.0 and ToxProfiler spin columns are already on the market.
On where development of ToxProfiler stands currently, Callewaert told ProteoMonitor this week that the company is “just starting with our first markers for liver, kidney, and lung damage using animal models that are well-characterized, and using proteomics techniques, proteins that are specific for each of those organs, and which are oxidized when the organ is exposed to a toxin that is specific for that organ.”
Oxford entered into proteomics by accident, Callewaert said. Founded in 1984, the company had focused its energies on protein purification and assay development. Its first product was the enzyme that aspirin, ibuprofen, and non-stroidal anti-inflammatory drugs inhibit. When Cox-2 inhibitors, such as Vioxx and Celebrex came along, however, research into their precursors slowed down, causing Oxford to look at other segments for business development, a circumstance that was unchanged by the Vioxx meltdown.
In 2004 Merck voluntarily withdrew Vioxx from the market over concerns that long-term, high-dosage use of the drug raised the threat of heart attack and stroke. Numerous lawsuits have been filed against Merck alleging harm resulting from use of the drug.
In the meantime, Oxford segued into immunoassays and then oxidative stress research. Today, the biggest market for Oxford, Callewaert said, is in the area of biomarkers for oxidative stress, specifically an oxidized lipid called isoprostane. The company markets a kit designed to detect and quantify isoprostane markers in serum, urine, and tissue culture.
In the course of doing ongoing research into oxidative stress, the company’s senior scientist, Thomas Brown, developed the ToxProfiler platform with the help of SBIR grants. The product was initially meant to be developed as assays for liver and kidney toxicity “and the initial market for this would be [for] pharmaceutical toxicity testing, where largely now, animals are sacrificed at different time intervals and pathologies are done,” Callewaert said.
The animal-based testing model is both expensive and time-consuming and uses a large amount of animals, he said.
“If that could be replaced with assays of serum at different time intervals on the same animal to get surrogate markers for organ damage and the mechanism of damage, there’s a huge market for that,” he said.
That started Oxford down the proteomics pathway, and in the midst of doing work on ToxProfiler, the company encountered the same problem that almost every proteomics researcher has faced at some point — high-abundance proteins. And that led to the development of ProteoMine, an immunoaffinity resin based on a mixture of polyclonal antibodies.
While several other companies, such as Sigma-Aldrich, Agilent Technologies, and Beckman Coulter, have depletion columns, ProteoMine was developed as a single-use product.
In contrast, its competitors’ are monoclonal-based columns that are meant to be recycled up to 200 times. Aside from significantly lower costs, Callewaert said that Oxford’s polyclonal-based ProteoMine has higher affinity.
“I come from academia and everybody thinks monoclonals [are best for protein depletion] because they’re so highly specific, but they tend to have less affinity,” he said. “Their binding constants to proteins tend to be lower than polyclonals. So actually, a set of polyclonals like in our products provides you a lot higher binding and captures high-abundance proteins very strongly.”
“If that could be replaced with assays of serum at different time intervals on the same animal to get surrogate markers for organ damage and the mechanism of damage, there’s a huge market for that.”
ProteoMine achieves up to 98-percent depletion of abundant proteins, Callewaert said. For individual researchers doing single proteomics projects — as opposed to core facilities that may be working on several assignments at once and so would have more use for a monoclonal column that can be recycled — ProteoMine is of particular use, Callewaert said.
“Frankly, how many people doing individual projects … are going to run 100 samples?” he said.
CAPitalizing on Some Help
Last month, Oxford announced it was one of 75 companies chosen to participate in the CAP program. Lasting 10 months, CAP is intended to help SBIR Phase ll grantees gain access to investors and industry representatives.
Each grantee is assigned an adviser who helps them map out a strategy to bring its product to market, obtain financing if necessary, and to seek out potential partners. Oxford’s adviser is Brian Taylor, president of and principal consultant at Growing Company Solutions, a Washington DC-area based consulting firm, and former director of global strategic marketing at Qiagen.
According to Taylor, now is a good time for the proteomics field, even if the predictions from five to 10 years ago of a proteomics boom haven’t materialized. With the field concentrating now on biomarker discovery, companies developing tools to facilitate that stand to do well, he said.
Because he and Callewaert met for the first time only two weeks ago, the two are still in the early stages of their mentoring relationship.
“We’ve talked about the product, we’ve talked about the potential applications of the products, we’ve talked about potential partners,” Taylor said.
While some firms in the program are looking for venture capital funding, Callewaert said Oxford, which has been profitable for most of the past few years, is looking for original equipment manufacturer agreements, joint venture deals, and equity investment.
“And so we’re preparing a portfolio to talk to some of the major proteomics companies,” he said. He declined to identify them but said they are “some of the Tier 1 tools companies.”
Together with ProteoMine, ToxProfiler would address an estimated $1.1 billion market for in vivo toxicology screening by pharma.
“We’re open to capture 10 to 20 percent of the total market, which is a big number,” Callewaert said.
The timeline to bring the array version of ToxProfiler to market depends on funding, Callewaert said. The company has relied largely on SBIR grants to develop the platform, but if it can joint venture with an established array company, it would hasten development of the product.
He said that ProteoMine 2.0 could make it to the market within the year, “but there’s development, as well as validation, and [quality control], and manufacturing start-up.
“We’re new to proteomics, and we’ve been more of an immunoassay company and oxidative stress company in terms of our product line,” Callewaert said. “So the quickest way to market is to partner with somebody that’s much better known in proteomics.”