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Cyntellect Snares First Customer for HT Cell-Based Drug-Screening Applications

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Fresh off its official incorporation as a company, San Diego-based Cyntellect announced last week that it has entered into a research agreement with Japanese drug maker Daiichi, which will use Cyntellect’s high-throughput cell imaging and laser-based manipulation technology for cell-based drug discovery.

Under the terms of the agreement, Cyntellect will design, configure, and run cell-based assays on its LEAP (Laser-Enabled Analysis and Processing) platform against a compound collection provided by Daiichi.

Specific financial terms of the deal were not disclosed, but Daiichi spokesperson Koichi Ando this week told Inside Bioassays in an email that the terms called for Cyntellect to screen Daiichi’s compound collection at Cyntellect’s San Diego headquarters.

He declined to provide information about the types of drug targets or therapeutic areas for which it would be using LEAP.

“Our researchers … [use] general cell-based assays,” Ando wrote in an e-mail to IBA. “Cyntellect has excellent technologies in cell-based assays. We especially evaluate[d] that LEAP is one of the best … laser-based cell-manipulation technologies.”

Cyntellect now hopes the Daiichi announcement will spur additional sales and partnerships for larger-scale drug-discovery applications. Jim Linton, Cyntellect’s chief business officer, said the company will likely continue to depend on such sales and partnerships for revenues, as opposed to actively pursuing venture capital.

“We’re not aggressively pursuing VC, but we’re always looking for financing opportunities,” he said. “We’re relying on alliances, product sales, and opportunistic financing.”

Linton also declined to provide any further details of the Daiichi collaboration. However, he provided an overview of how LEAP might be used in cell-based drug discovery.

“Either in a primary screen or secondary screen, LEAP offers the ability to permeabilize cells and allow you to deliver small molecules into the cell without affecting [it],” Linton said. “Secondly, LEAP offers [an] active processing mode. So you can imagine somebody screening for an ion-channel responsive cell, and wanting to measure the kinetics of that cell. You may plate a thousand cells, but by nature these cells are very heterogeneous.

“So you throw your drug in, and now you want to look at the cells that are only ion-channel responsive,” Linton added. “You can have the system identify those, and then basically eliminate the cells that are not responders.”

Based on these capabilities, LEAP can thus be used as a cell-based assay development tool, or to purify cell populations in higher-throughput screening modes, according to Linton.

The Daiichi announcement comes on the heels of Cyntellect’s announcement in February that a merger with two branches of original parent company Oncosis has enabled it to consolidate all assets from those branches, including IP, into one entity: Cyntellect Inc.

Whereas Cyntellect at one time seem poised to focus its attention on therapeutic applications for LEAP, both recent announcements seemingly signify a full-fledged transition for Cyntellect into a tools provider for basic laboratory research and high-throughput cell-based drug discovery.

When Cyntellect spun out of Oncosis in 2002, it did so as an R&D arm committed to commercializing LEAP for research applications. Meanwhile, Oncosis indicated that it would continue to focus on developing a platform called Photosis — which is based on the same basic laser-enabled technology found in LEAP — as a therapeutic technology. Specifically, the first application was to be the elimination of tumor cells from autologous stem cell transplants in non-Hodgkin’s lymphoma patients.

Although Cyntellect hasn’t indicated whether it is completely phasing out LEAP for therapeutic transplantation, the company hasn’t released news regarding this application since the spin-out occurred. In a long list of potential LEAP applications on Cyntellect’s website, processing of cells for therapeutic transplantation is last.

Now, according to Linton, the company will focus on three main application areas for LEAP: cell purification, high-throughput opto-injection, and a combination of the previous two capabilities for high-throughput cell-based drug screening such as outlined in the Daiichi announcement.

“In the areas of opto-injection, the applications can relate to everything from functional proteomics, to functional genomics, to general DNA transfection, to intracellular small-molecule screening,” Linton said. “In the cell-purification space, there’s everything from cell line development to cell line development in pharmaceutical manufacturing, to sample preparation, to cell therapy.

“Those are very broad categories, and … the plan is to find the places where we can make a real difference and complement the entire spectrum of automation and instrumentation people have in the lab,” Linton added.

The LEAP platform’s diverse array of applications is enabled by a laser that is trained on cells via a digital micromirror array. The laser is used strictly for cellular manipulation, while imaging is performed using LED and xenon arc lamp excitation coupled with CCD cameras.

The entire imaging system is computer-controlled, and features object recognition software that is looped back to the laser-processing capabilities. Imaging can be done in three modes, Linton said: brightfield, darkfield, and fluorescence.

In October, Linton told Inside Bioassays that the company was also working on a “benchtop” version of LEAP, to be called HOP (High-Throughput Opto-injection), and that such a platform would be available by the middle of this year (see Inside Bioassays, 10/26/2004). Last week, Linton declined to comment whether that timeline was still valid, but said that the company definitely still plans to release HOP.

“They’re both benchtop devices,” Linton said. “But the LEAP system is the size of a large flow cytometer, and the HOP system is the size of a laser printer.”

For now, Cyntellect will continue to market LEAP, and the company’s eventual goal, according to Linton, is to sell the technology as a “three-in-one” tool for drug discovery and basic research.

“If you look at the cellular [assay] marketplace, there are really three things that people primarily do,” Linton said. “They either do cell purification, cell transfection, or cell imaging.

“Each of those are done on independent platforms, and in different formats — some are in cuvettes, some microwells, some test tubes — so to conduct any combination of those, you’ve got to change systems, change operators, and change formats, and that all gets away from the entire goal, right now, which is to streamline workflow,” Linton added.

The company has found some early success in tackling each of the three application areas separately, as it has enjoyed a steady stream of partnerships, customers, and grant money over the past two years. In December, Cyntellect forged an agreement with Protein Design Labs to use CellXpress — which is based on LEAP — for selecting cells with the highest level of antibody production. In February, it announced a similar deal with an as yet undisclosed US-based biotechnology firm.

In addition, in September, the company won a Phase II $1.5 million Small Business Innovation Research grant from the National Institutes of Health to continue to develop RNAi delivery applications on LEAP. This follows on the heels of two SBIR grants of an undisclosed amount awarded to the company in 2003 for similar applications from the NIH and the National Science Foundation.

— BB

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