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Italian Biotech Newron Wins 1.8M From EC to Lead Ion Channel Screening Project

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Italian biotechnology firm Newron Pharmaceuticals will receive €1,833,160 ($2,465,462) from the European Commission to develop an “innovative integrated system for efficient high-throughput screening of molecules for ion channel targets,” the company said last week.

Newron, which focuses primarily on CNS-related drug discovery, will use the funding to manage a consortium of “small-to-medium enterprises” and universities from five European countries — Italy, Germany, Romania, Hungary, and Poland — as part of a research initiative dubbed the ION project.

Awarded under the European Commission’s Sixth Framework Program (FP6) for Research and Development, the funding was established to “create some competition in Europe” in the area of high-throughput ion-channel screening platforms, according to a Newron official. Broadly, it was implemented by European parliament in 2002 to foster European competitiveness and create jobs in a variety of markets, particularly technology.

The four-year FP6 program has a total budget of €17.5 billion, €2.3 billion of which is earmarked for life sciences research, GenomeWeb News, Inside Bioassays’ sister publication, reported in June.

The ION project award derives from the FP6 cooperative research scheme for small-to-medium enterprises, which encourages collaboration between European nations and, along with its sister collective research program, has a budget of approximately €430 million.

Last week, Patricia Salvati, vice-president of discovery at Newron and scientific coordinator of the ION project, told Inside Bioassays that the thrust of the project was “to create some competition in Europe” in the area of high-throughput ion channel screening platforms, many of which she claims are cost-prohibitive for smaller companies such as Newron.

In addition, Salvati said, the consortium would like to improve upon current technologies being used for ion channel screening.

Electrophysiology-based ion channel drug discovery “is a huge bottleneck,” Salvati said. “The whole idea is to improve the screening process, and not just to study a single molecule,” as might traditionally be the objective of a company such as Newron.

“It’s not a huge grant, so we cannot solve the problem of [drug] discovery with this,” she added. “But we will do something that we think is really practical and useful.”

That “something,” Salvati said, is to take an ion channel screening platform manufactured by Multi Channel Systems, which Newron has used since its inception, and create a next-generation platform that will not only be useful to Newron, but will also be commercially available once the project is completed.

“It’s a mixture of everything,” Salvati said. “Central to this is certainly the improvement of electrophysiology machinery. For this reason, one of the partners of the consortium is Multi Channel.”

Multi Channel, based in Ruetlingen, Germany, specializes in high-performance measuring instruments and equipment in the field of electrophysiology. Its electrophysiology platform, Roboocyte (a combination of ‘robot’ and ‘oocyte’), is a 96-well plate-based instrument that Newron has used since it was spun off from the CNS discovery group of Pharmacia Upjohn in 1998.

“It’s a 96-well plate, so it’s sort of high-throughput,” Salvati said. “When you talk about electrophysiology, it’s never really high-throughput — it’s more like medium. But it’s working reasonably well, and at the end of the day, most of the data is viable.”

But Roboocyte also has some limitations, Salvati said. “We’re using it because we bought it in the past, and the idea came to try and work on it and improve it,” she said. “Multi Channel will contribute by improving the hardware. So we’ll have a machine that is second-generation as compared to the one that’s commercialized today.”

An example of one of those changes is altering Roboocyte from a two-electrode voltage clamping system to single clamping, a technical difference that, Salvati said, will “make the system more suitable for working with different channels.”

Though Salvati didn’t disclose the price of the Roboocyte, she claims it is significantly lower than electrophysiology instruments from US companies such as Molecular Devices (and recent acquisition Axon Instruments), and is one of the main reasons the company purchased it in the first place, Salvati said.

“The idea was to try and improve a European company’s machinery since we were applying for a European grant,” she said. “We would like to create some competition in Europe, considering that some of this high-throughput electrophysiology machinery, like [PatchXpress] from Axon, can cost up to €500,000.”

In addition, she said, most of the instruments currently on the market are not validated for a variety of ion channel assays, “so you spend a lot of money and you’re really not sure what you bought,” Salvati said. “IonWorks [from Molecular Devices] is the most validated. But that is more of a blind way of screening — a single well is one point, you don’t build up a dose-response curve, and you don’t know if the data is good. It’s a 384-well plate, but it’s blind,” she said.

Other Players

SC IT Romania, an emerging software company based in Cluj, will contribute to the consortium by developing an improved software platform for analyzing and storing data from the new instrument. Meanwhile, Nikem Research, a chemitechnology company based in Milan and spun off from GlaxoSmithKline, will synthesize compounds to be used in testing the new platform.

The academic participants — the University of Debrecen in Hungary, Universita degli Studi di Firenze in Italy, the Polish Academy of Science, Istituto Richerche Farmacologiche Mario Negri in Italy, and Politecnico di Milano — will primarily contribute in vivo models of CNS disease for corroborating the small-molecule work, Salvati said.

“These centers of excellence are going to prove that the molecules that we’ve selected to improve the screening process are actually active in different pathologies of CNS,” she said.

The small-to-medium enterprises, with whom the intellectual property will reside, stand to gain financially when all is said and done. Salvati said that Newron will retain the IP related to small molecules, MultiChannel will retain the IP related to the new instrument, and SC IT will retain the rights to selling the software.

“And we will also profit from it because we can use the new machine, we can use the software, and it’s something we can share with our partners,” she added. “And we will have a lot of pharmacology and animal models with some selected molecules, so there’s a lot in it for us.”

Molecular Devices and other competitors need not worry about the competition quite yet, as the project has a two-year timetable.

“We have to do a business plan, et cetera,” Salvati said. “But everyone is interested in commercializing this as soon as possible. I think for the platform, two years will allow for a better machine.”

Salvati said that Newron hosted the consortium’s kick-off meeting on Dec. 3, and will “start the work immediately,” with the first initiative being an internet portal open to the public “in the near future.”

— BB

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