As the demand for high-throughput cell-based screening of potential lead pharmaceutical compounds increases, Sunnyvale, Calif.-based Molecular Devices is looking to enhance its market presence in this area.
Though not yet complete, the company’s planned acquisition of Axon Instruments of Melbourne, Australia, is expected to fortify its platform for screening the interaction of compounds with cellular ion channels, a major therapeutic target in central nervous system and cardiovascular disorders.
The original announcement was made on March 21, and at the time, Molecular Devices told Inside Bioassays’ sister publication, BioArray News, that Axon’s microarray scanners would boost its genomics business (see BioArray News, 3/24/04).
But in a March 22 conference call, Tim Harkness, Molecular Devices’ vice president of finance and CFO, characterized Axon’s business as only being about one-third genomics related. The other two-thirds, he said, were evenly split between cell-based screening and neuroscience, areas where Molecular Devices also stands to benefit.
Axon offers two platforms that fall into the high-throughput cell-based screening arena: the ImageXpress automated cellular imaging and analysis system, and the PatchXpress automated parallel patch-clamp system. Molecular Devices sees the Axon products as complementary to its own similar offerings — the Discovery-1 high-content imaging system and the IonWorks HT electrophysiology system.
“Axon’s PatchXpress system offers automated patch clamping with lower throughput, but greater flexibility than Molecular Devices’ IonWorks HT,” said Molecular Devices CEO Joseph Keegan in the conference call. “Axon’s ImageXpress high-throughput imaging system addresses similar applications as Molecular Devices’ Discovery-1, but using a different technological approach.”
This week, Steven Oldfield, vice president of marketing for Molecular Devices, told Inside Bioassays that the PatchXpress will likely be the most beneficial acquisition in terms of cell-based assay products.
According to Oldfield, pharmaceutical development is dominated by three major drug targets: G-protein coupled receptors (GPCRs), kinases and phosphatases, and ion channels. He said that GPCRs are the most heavily targeted, constituting about 29 percent of screening targets, closely followed by kinases and phosphatases at about 20 percent.
At nine percent, “ion channels are currently the smallest area in terms of number of compounds being screened … and the number of drugs that currently address that area … but potentially drugs that target ion channels may be the most important [in the] long term,” Oldfield said. “We’ve got platforms that work in all three areas. With the Axon acquisition, we’ve strengthened our ability to look at ion channels.”
Patch clamping is traditionally a manual technique, and although it has generated a great deal of information about the function of cellular ion channels, it is labor-intensive and time consuming. According to Oldfield, a lab technician can manually perform approximately 15 measurements per day, but using IonWorks can do about 3,000 per day.
Axon says that the PatchXpress system can screen only about 2,000 compounds against ion channels in an eight-hour day. But PatchXpress offers two capabilities that IonWorks does not — initial cell-attached resistances of greater than 1 Gigaohm, which may be more important for ion-channel safety profiling, and the ability to screen ligand-gated channels — which is why Molecular Devices sees the relative strengths of each instrument as complementary.
Molecular Devices and Axon are the two major players in the automated high-throughput patch-clamping field, which bodes well for Molecular Devices to dominate once the acquisition is complete.
But therapeutic targets are only part of the story. To gain broader insight into how cells react to a given situation, many researchers are turning to high-content fluorescence imaging. Molecular Devices’ Discovery-1 and Axon’s ImageXpress platforms face stiffer competition in this area, as numerous companies have developed or are developing automated microscopy systems.
ImageXpress investigates cellular characteristics such as apoptosis, viability, neural outgrowth, cytoskeletal rearrangement, trafficking, and subcellular molecular localization. The Discovery-1 has a more limited range of applications, but does have a module for tracking angiogenesis, which is being heavily explored in the development of cancer therapeutics.
In addition, the Discovery-1 uses MetaMorph image analysis software, which Molecular Devices adopted in its 2002 acquisition of Universal Imaging Corp.
It is unclear at this point whether Molecular Devices will continue to support both product lines, but both companies stated that they are developing newer, higher-throughput versions of both the PatchXpress and IonWorks.
“The objective of the combined company would be to offer a family of solutions in the automated patch clamping and electrophysiology area,” Keegan said.
“[Cell-based assays are] only increasing in importance,” Oldfield said. “I think all of the pharma companies are reporting that [they] will use more cell-based assays going forward. Libraries of compounds have increased almost exponentially. It might be that people are getting more directed in their screening. They’re spending more time analyzing compounds up front.”
Oldfield also said that pharma consolidation has increased the importance of screening. “Two libraries come together, and people say ‘we can’t screen all that; let’s look at which of them still make sense.’ I don’t think it’s reduced the amount of screening that’s gone on, because the libraries have increased that much anyway. The pressure comes in trying to miniaturize and reduce costs during the screening process,” he said.
The acquisition, Oldfield said, is not expected to be completed until sometime before June. In the meantime, Molecular Devices will disclose its first-quarter 2004 earnings on April 22. A conference call to discuss the results is scheduled at 11 AM EST on the following day, April 23, along with a webcast accessible at www.moleculardevices.com.