SAN DIEGO — German instrumentation manufacturer Multi Channel Systems has a cell-based assay technology that it thinks can significantly improve cardiac safety profiling in drug discovery, and is looking for its first customer.
The company may have received just the boost it needed for its fledgling technology at IBC’s ScreenTech/TargetTalk conference held here last week, as it was deemed the most promising and innovative technology at a session in which industry representatives evaluated emerging drug-screening technologies.
The session, entitled “Emerging Technology Idol,” consisted of eight researchers from companies and academic institutions delivering presentations on relatively new technologies for drug screening. Each technology was rated from one to 10 in two categories: innovation and “applicability,” or its potential to be a marketable product.
Although it was far from a scientific rating method and a rather informal competition, the drug-discovery take on television talent show “American Idol” was one of the more interesting sessions of the three-day conference, and was aimed at providing insight to the presenters about their technologies’ potential.
Of the eight technologies, four featured a significant cell-based component, three were slanted more towards biochemical assays, and one dealt with small-animal phenotypic screening.
When all was said and done, it was a cell-based assay — the last presentation, given by Thomas Meyer, head of cardiovascular research and development at MCS — that carried the day, winning praise from all three panelists for both innovation and market potential.
The product that Meyer presented is called the QT-Screen, and is currently available for purchase, but “still in the final development stages,” Christine Leifgen, a product manager and technical communicator for MCS, told Inside Bioassays last week.
“At the moment, we are looking for our first customer,” Leifgen said. “It would probably be best if that customer were in Germany or in Europe, but maybe there would also be the possibility that the first customer be somewhere else abroad.”
The QT-Screen is intended to do just what the name implies: screen potential compounds against living primary cardiac myoytes to assess the drug’s potential to cause QT interval prolongation, one of the foremost considerations for drug makers when considering cardiac toxicity of a compound.
Unlike many cell-based assays on the market that cater to the “high-content” trend of extracting as much information as possible out of cells, MCS focused on producing an instrument that does one specific thing, and does it well: measuring the action potential of cardiac myocytes.
Leifgen said that the company recognized a market opportunityin this area soon after the US Food and Drug Administration last year released its S7B guidelines for QT interval prolongation testing, entitled “The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization by Human Pharmaceuticals.”
The significant portion of the guidelines, which can be seen here, discussed the importance of in vitro electrophysiology studies using single- or multi-cell preparations. Currently, the most common way to conduct this testing is patch-clamping of single cells, followed closely by ion-channel assays on non-cardiac cells expressing specific channels.
MCS thinks it improves on both of these methods by providing higher throughput than patch-clamping, and more relevant data than non-cardiac cell-based assays. The QT-Screen comprises a 96-well plate, and each well contains a recording microelectrode and a reference microelectrode.
Primary cardiac myocytes are grown in each well such that the recording electrode is close, but not touching, the cell. This is in comparison to most other electrophysiology techniques in which a probe disturbs or pierces the cell membrane. The cells are also grown in such a way that they can interact with one another and beat spontaneously, providing a close approximation of cardiac tissue.
“You always see the complete tissue, and the interaction of cells in the tissue,” Leifgen said. “This is in comparison to, for example, patch-clamp techniques, where you typically only have a single cell.
“In addition, you have native myocytes,” she added. “You don’t have a special cell line that is artificial, where you bring, for example, a receptor into it through molecular techniques. Also, in many non-electrophysiology assays, you have single receptors. But in this case, you not only have the complete cell, but also a complete tissue and layer of cells.”
Different compounds can then be added to each well while the recording electrode measures changes in action potential. A similar measurement technique has been well-proven in neurobiological studies, Lefigen said.
“Most microelectrode array techniques have a lot of electrodes, about 60 electrodes, but you can only put a single compound on all 60 electrodes, so it is more for lower or medium throughput,” Leifgen said. “The QT-Screen is intended for higher throughput. You have a 96-well plate, and you can apply multiple compounds on a single well plate, and therefore have much higher throughput. We intended it for pharmaceutical research, while [other] microelectrode arrays are more for basic research.”
One of the panel members at ScreenTech was Al Kolb, the president elect of the Society for Biomolecular Screening and president of KeyTech Solutions, a drug-discovery technology consulting firm. He said that the QT Screen represented what happens in the entire system better than many other cell-based assays on the market.
There are a lot of models that people try to use to mimic what organisms are doing, and some of them are more accurate than others,” Kolb told Inside Bioassays last week. As an example, he said that Caco, a cell-based assay used for measuring the absorption of compounds, is designed to mimic the lumen of the intestines.
“That’s used widely, but there are a lot of questions about how closely it really mimics the lumen of the gut,” Kolb said. “There are a lot of other cell-based assays like that, which are probably better than biochemical assays, but a far cry from what’s going on in the system.
“The Multi Channel Systems technology really is measuring the cardiac rhythm,” he added. “Whether a group of cells can mimic a whole heart is a question, but you really are looking at what the cardiac rhythm of the entire heart is.”
Another panelist, Thomas Large, head of neuroscience discovery at Eli Lilly, said that he believed the QT-Screen would have a high degree of applicability within the drug-discovery industry, and that it likely had the best chance of commercial success of any of the technologies presented. Furthermore, all the panelists agreed that the MCS system had a high degree of applicability considering the recent hERG-related cardiac toxicity failures of blockbuster drugs.
Meyer’s presentation seemingly went a long way toward attracting potential customers, he said, but MCS thinks that some improvements can still be made on the biology side of things.
“I think we have some interest at the moment, but I think we also have to do some more development,” he told Inside Bioassays last week. “We definitely have to find a cell line that is more suitable for these things. It works perfectly fine now, but it would really be a break-through if we get the stem cells working on a larger scale. That, at the moment, is a bit of a bottleneck for sales. Otherwise, the machine is running in our lab, and could be ready for sale momentarily, but the biology is the bottleneck.”
Leifgen said that the company currently estimates a list price for the platform at about €150,000 ($194,000), although she said this price would be significantly discounted for MCS’ initial customer.
“The first customer, of course, will not have all the features, and also will have to do some testing with the system, but they will also get a special price,” she said.
Zebrafish Finish Second
The “second-place” technology was also a systems biology approach, but at one level higher than that of an individual cell: DanioLabs’ combinatorial chemistry approach to conducting phenotypic screens on live zebrafish. DanioLabs already sells drug-discovery services in which it utilizes the zebrafish assays, and it has also recently secured about $6 million in VC funding to nurture its internal drug-discovery business using the same approach (see Inside Bioassays, 1/25/2005).
Panelist Iris Pribilla, a research group leader for French biotech CisBio International, noted that while DanioLabs’ chemistry approach was innovative and that there was a sizeable market for such an assay service, zebrafish assays have been around for a while and were not particularly innovative in an of themselves.
Kolb added that although they represented a complete system, “zebrafish are still zebrafish,” and their proximity to rat or human systems was debatable.
The other presentations in the “technology idol” session were:
• Excellin Life Sciences, for its not-yet-available electroinjection technique for “universal molecular delivery into cells” (see Inside Bioassays, 10/26/2004);
• Nascent Biosciences, for single-use “PocketTips” for nanoliter reagent transfer;
• SpinX Technologies, for its benchtop kinase profiling with programmable microfluidics (which received some of the highest marks on “innovation,” though it is strictly a biochemical assays system);
• Peter Kuhn, an associate professor of cell biology at the Scripps Research Institute, for “enthalpy arrays” for a wide variety of biochemical screens;
• Acea Biosciences, for microelectronic sensor arrays for label-free monitoring of receptor-ligand interactions on living cells (see Inside Bioassays, 1/18/2005);
• BioSeek, for its BioMap human primary cell assay systems (see Inside Bioassays, 3/8/2005)