Belgian biotech startup Remynd this week said it has licensed its yeast cell-based genotoxicity screening system to drug-discovery firm Galapagos, also located in Belgium, which will use the assay technology in its internal early-stage drug-development programs.
Remynd, a 2002 spin-off from the University of Leuven, hopes that the non-exclusive deal attracts more customers for the assay technology as the company nurtures its own internal drug-discovery programs in Alzheimer’s and Parkinson’s disease.
The assay technology, called RadarScreen, consists of genetically engineered yeast cells featuring a β-galactosidase enzymatic reporter. Remynd says that the cells can be screened against compounds of interest to determine their potential genotoxicity much earlier in the drug-discovery process than most genotox assays.
“If you have a compound that is genotoxic or supposedly genotoxic, it will lead to DNA damage,” Stefaan Wera, Remynd’s CEO, told CBA News this week. “This will activate DNA repair genes and the entire cellular DNA repair system. We have kind of hijacked that system and coupled that to a reporter. That part of the technology is fairly straightforward.”
Where Remynd’s technology differs from most other genotoxicity assays is in its use of yeast cells, as opposed to bacterial or mammalian cells.
“We also have plenty of experience with using yeast cells for screening purposes, and therefore we have used our proprietary strains to implement this technology,” Wera said.
The particular yeast strains that Remynd uses in RadarScreen have had several ATPases and other molecules deleted, according to Wera. These ATPases and other molecules typically “bump” genotoxic compounds out of yeast cells.
According to Wera, this modification “increases sensitivity significantly, so the resulting system is a highly sensitive cell-based assay for genotoxic compounds.”
Remynd chooses to work with yeast cells because they are relatively inexpensive and easier to work with than mammalian cells. In addition, Wera said, yeast cell-based assays are comparatively highly reproducible, at least for this particular genotoxicity assay.
“If you look at the Z-prime values, which measure quality and robustness of these assays, it’s extremely elevated,” Wera said. “The yeast-based assays that we do here routinely have a Z-prime value of above 0.85, and you could never reach that with some other assays, because the variability of yeast cells is very low.”
Of course, measuring the potential genotoxicity of compounds intended as eventual human therapeutics raises some relevancy questions, which Wera acknowledged.
“Of course a yeast cell is not a human being,” Wera said. “It does not replace genotoxicity testing at later stages of drug development, but it will increase your success rate because you will get rid of a lot of genotoxic compounds at the very early stages of your drug development programs, which will save a lot of money.”
According to Graham Dixon, Galapagos’ senior vice president of drug discovery, relevancy is not a huge problem. “Yeast, being a eukaryote and closely related to mammalian cells, is used routinely in drug discovery for convenience,” Dixon wrote to CBA News in an e-mail. “The type of assay we are using in this case would be very difficult to produce and use in human cells.”
In addition, the relevancy issue has already been addressed – somewhat – as Remynd is not the first company to exploit yeast cells as a genotoxicity screening tool. Most notably, British biotech Gentronix has been selling a yeast-based genotoxicity screening system under the brand name GreenScreen GC since it was founded in 1999.
In August, Gentronix founder and CSO Richard Walmsley told CBA News that the firm has been fairly successful in selling GreenScreen GC to pharmaceutical and biotech customers. Its most well-known customer, Johnson & Johnson, published a research paper with Gentronix in the November 2005 issue of the journal Mutagenesis validating the yeast-based assay in a pharmaceutical screening environment.
GreenScreen GC, however, uses a GFP reporter instead of a β-galactosidase reporter. What’s more, Gentronix has developed a human cell-based assay based on the same technology in response to multiple customer requests.
“You could do [a primary screen] with, say, a classical Ames test or something like that, but it would be extremely expensive and time consuming.”
To be fair, Gentronix’s test is intended to be used as a way to clarify confusing results generated by existing genotoxicity assessment methods, such as the classical Ames test, while RadarScreen is intended more as a primary high-throughput cell-based screen.
“You could do [a primary screen] with, say, a classical Ames test or something like that, but it would be extremely expensive and time-consuming,” Remynd’s Wera said. “[RadarScreen] allows you to do that screen at a very low cost and in the very early stages of your program to avoid a lot of problems afterwards.”
In fact, Galapagos was using the Ames test for early-stage genotoxicity screening before its deal with Remynd. “As the Ames test is quite resource-intensive and expensive, we were looking for a more cost-efficient ‘pre-test’ to screen better candidates for the Ames test,” Galapagos’ Dixon wrote in his e-mail. “The [Remynd] technology is amenable to high-throughput filtering, making it a good solution for a ‘pre-test.’”
Dixon added that Galapagos did evaluate other technologies for an Ames pre-test, but that RadarScreen “came out of the evaluation as the most cost-effective solution.”
Remynd hopes that the sale of the assay to Galapagos will help validate the technology and spur additional licensing agreements with other pharma and biotech partners, which will go a long way toward supporting Remynd’s internal Parkinson’s and Alzheimer’s drug-discovery programs.
Remynd, like Galapagos, has a mixed business model and provides contract research work in the areas of neurodegenerative disease.
“This is a recently developed technology, but it’s actually not our core technology,” Wera said. “We work on Alzheimer’s and Parkinson’s, and we needed this tool in house, so we developed it. There appeared to be interest from some of our partners, so we decided to go ahead and license it out.”
And even though the two companies sport similar business models (though Galapagos is much larger), and are located a few miles from one another, the RadarScreen deal does not necessarily portend additional collaboration between Remynd and Galapagos, Wera said.
“I think it’s too early to say, but … we are both in Belgium … and of course it makes it easier to exchange ideas and start collaborations,” he said. “But there is no immediate plan.”