As part of its small-molecule screening initiative, the National Institutes of Health's Chemical Genomics Center will use cell lines made by Odyssey Thera that incorporate the firm's protein-fragment complementation assay technology, the company said earlier this month.
Odyssey's other deals and partnerships — mostly with pharmaceutical companies — have strictly been screening contracts using the PCA technology, but the NIH collaboration is the first in which Odyssey will supply specific engineered cell lines to its partner. The agreement also underscores the tool's value to the company as it fosters its own internal drug-discovery program.
Terms of the deal call for Odyssey to provide three systems to the NCGC, Jim Inglese, the center's deputy director, told CBA News last week. "They're three different signaling components in a cell, and [they] represent a swath of biology of general interest and contain proteins that haven't been studied in any great detail."
The concept behind PCA is relatively simple: Cells are engineered to express fragments of a fluorescent protein, such as GFP, on separate cellular proteins that are suspected to interact. If the cellular proteins do interact, then the fluorescent protein fragments are brought together, resulting in a fluorescent signal.
"When you have an assay that reads out a particular protein, interaction, or pathway, how many customers are there for that? So economically, I'm not sure that selling these as reagents — as a single assay at a time — is such a compelling model."
The power of this, according to Inglese, is that researchers can "dissect" specific components of a particular signaling pathway.
"Odyssey's technology allows you to generate sensors that can delimit any part of the pathway," Inglese said. "For example, take a pathway of 20 or 30 proteins, and then there might be regulation by another pathway from the side. With [PCA] you can actually put in a sentinel or sensor in any part of the pathway.
"If I want to know what's happening from the cell membrane on down [through] several proteins to some kinase, I can rig the kinase so that when it's activated, it signals," he said. "You can limit that pathway so it's dissected, but still work with it in the cellular context."
This capability fits well, Inglese added, with the NCGC's mission to screen its repository of more than 100,000 small molecules against specific cellular pathways.
"You can also potentially start analyzing the activity of proteins in pathways whose function isn't clear," he said. "So we can move closer to finding small-molecule modulators of proteins of uncertain function, and that's one of the things we find attractive about it."
Protecting the Cash Cow
Odyssey was also recently awarded its first European patent, No. EP0966685, for the PCA technology, and last week garnered its seventh US patent, No. 6,929,916, for the assay (see Patent Watch, this issue). The newly issued patents provide the company with broad worldwide coverage for its flagship technology.
It is not clear how much revenue Odyssey is pulling in from agreements involving the PCA technology, as the privately held firm does not disclose its revenues. In the past year, however, Odyssey has disclosed several corporate screening partnerships surrounding PCA, including with drug makers Merck, Pfizer, and Bristol-Myers Squibb. MacDonald also declined to share financial details surrounding the newly penned NIH agreement.
Although Odyssey hasn't made any announcements regarding its internal drug- discovery program, and doesn't allude to its progress on its website, MacDonald told CBA News that the company plans to continue moving forward with it.
"We're quite interested in expanding our drug-discovery program," MacDonald said. "I think the value here is just getting to drugs, and the question is who can get there faster, and more efficiently."
"We have very active potent leads with activity across a broad range of human tumor cell lines, and we're advancing those through pre-clinical stages," she added. "There are no filings yet, but this [program] definitely is working, and the [compounds] are as potent as the gold standard compounds in the clinic for those indications. And again, we're using the cell-based assays to do all of that work."
Odyssey's business model is not unique because several companies have previously cashed in on assay technologies as a way to support their own fledgling therapeutics programs. Some have fully shifted to drug discovery after selling the rights to their assay technologies outright, but maintain a license to use it in their own programs. One recent example of this strategy is Xsira Pharmaceuticals (formerly Norak Biosciences), which in March sold the rights to its Transfluor translocation assay to Molecular Devices in an $11 million deal (see CBA News, 3/15/2005).
Although MacDonald noted that "anything is possible," it appears as if Odyssey will hold on to its assay tech for the foreseeable future. In fact, MacDonald indicated that the PCA technology may be more appropriate as a part of Odyssey's in-house screening services.
"It's quite a new area, and one of the things that's unique about this area is that people who do screening have their own targets of interest," MacDonald said. "So you have your own favorite receptor, or favorite protein kinase, or whatever you're studying, and that might be somewhat unique to your project.
"When you have an assay that reads out a particular protein, interaction, or pathway, how many customers are there for that?" she asked. "So economically, I'm not sure that selling these as reagents is such a compelling model, as a single assay at a time."
Nevertheless, MacDonald sees early adopters such as the NCGC as being very important for eventually making PCA a more commonplace technology in industry. As an example, she pointed to the rapid uptake of DNA microarrays in the past several years after a relatively slow external adoption rate.
"The work was actually done at Affymetrix, and … in those days it was quite expensive, because these things were not mass produced," she said. "Eventually it became more of a mass-produced, high-throughput thing — people had instruments that were readily available to do those studies themselves, and the rest is history.
"I'm sure that will happen here, and I guess the question is, 'What is the time frame?'" she added. "It's certainly probably not five years, but I also am not sure it's in 2005. So it's just a question of adoption, and I think the early adopters like the NCGC are important, because they have been doing these kinds of assays, are not afraid of cell-based technologies, have the right instrumentation, realize it can be high-throughput, and understand how to use the results."
— Ben Butkus ([email protected])