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Start-Up Reify Starts Up Again With Cardiac Tox Screen Service Based on Imaging Platform

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Approximately three years after it was founded, Cambridge, Mass.-based biotech Reify last week launched a screening service for cardiac toxicity testing based on its flagship Visible Discovery automated imaging system, representing the company's first crack at a service-based business model.

Making its first "big splash" after somewhat retooling the company to focus more on product development, Reify debuted the service, called Myosight, at last week's American Heart Association conference in Dallas, Sean Walter, the company's vice president of corporate development, told CBA News.

"This is really kind of a relaunch of the company," Walter said. "In between last April and now, a lot of things changed about the company, and one is that we put our aims to raise venture money on hold in order to focus on developing the technology, productizing the technology, and moving the company forward that way. So we took some time to do that, and this is sort of the first big splash to move that forward."

With its new service, Reify hopes to tap into the market for testing early-stage drug candidates for cardiac toxicity. It is difficult to pin down an estimate for the size of this market, since pharmaceutical scientists currently use a combination of methods to assess the toxicity of compounds in several cell types, such as kidney and liver. However, cardiac toxicity remains one of the larger concerns, and its importance has recently been amplified with the recall of COX-2 inhibitors such as Vioxx and Celebrex.


"I see the biggest application of this in pharmaceutical drug screening, because you may be able to really cut down your number of compounds from thousands to a handful early on, and then go back and do more thorough studies on those drugs."

Myosight's selling point is its ability to assess cardiac toxicity in large, mixed populations of living heart cells. The Visible Discovery platform, on which the Myosight service is based, does this by using epifluorescent and phase-contrast microscopy combined with high-resolution video cameras to scan cell-culture plates and essentially create time-lapse videos of cells.

It seems, however, that anyone can build an imaging system these days, and like many other automated microscopy or high-content screening platforms, Reify believes its software is the driver. Walter said that the software is in fact the "core technology" that analyzes the time-lapse images to make several measurements of cardiac cell activity.

These capabilities are useful for a number of applications, such as measuring cell motility, cycle, and health. However, monitoring primary myocytes for cardiac toxicity screening appears to be the lowest hanging fruit, at least financially speaking, and an application for which the platform is ideally suited.

Using Visible Discovery, scientists can essentially monitor the cellular rhythm, relaxation kinetics, and contractility of heart cells in response to treatment with drug candidates. According to Ronglih Liao, an instructor of medicine at Harvard Medical School's Brigham and Women's Hospital who has been helping Reify test its technology, two methods are currently the most widely used to make such measurements, and neither is amenable to a high-throughput drug-discovery environment.

The first method is called edge detection, in which researchers measure the contraction and expansion of myocytes by imaging markers placed on either end of the cell. The second and more recently popular method is measuring the length of sarcomeres, the contractile units of striated cells such as myocytes and cardiac myocytes.

The problem with either of these methods, Liao said, is that "they are usually done one cell at a time." Besides being tedious and time-consuming, Liao said, researchers typically will want to see how a drug affects heart cells in a more natural environment — that is, in a heterogeneous population of cardiac myocytes as is typically found in the human heart. This is precisely what Visible Discovery enables because of its ability to scan multiple cells simultaneously on 96- or 384-well plates.

But that is only half the battle, as in order to test the effects of a drug on a heterogeneous population of cells, the researchers must also be able to identify which cells are which — some are healthy, functioning myocytes; while others are weak, abnormal, or otherwise inappropriate altogether. In this sense, Liao compares Visible Discovery's capabilities to fluorescence-activated cell sorting (FACS).

"It is similar to FACS, which is a very powerful immunohistochemistry tool that allows you to do many more cells at once," she said. In the same way, Liao said, Reify's technology allows you to identify different cell types, and then identify what is happening to each of them when you challenge them with a compound.

"I see the biggest application of this in pharmaceutical drug screening, because you may be able to really cut down your number of compounds from thousands to a handful early on, and then go back and do more thorough studies on those drugs," Liao added.

Walter said that Visible Discovery can currently assay anywhere from "dozens to hundreds of cells in a given well in a dish, and with a 96-well plate, you've got easily several thousand cells that you're analyzing in the course of an hour or a few hours."

Now Reify hopes pharma will find value in such a service. Since Myosight was just launched, Walter said the company doesn't yet have biotech or pharmaceutical customers, but claims the company was "aggressively" marketing the product at the AHA conference, and that it had "several productive conversations."

The Visible Discovery platform may be useful for several other types of assays, such as for cell motility and health, but Reify wants to keep most of these close to the vest.

"Visible Discovery has a lot of great applications, but we wanted to focus on this one because there are a lot of commercial opportunities that we'd kind of like to keep to ourselves in terms of finding new drugs, or fixing drugs that have an adverse cardiac effect," Walter said. "We'd rather be able to do that ourselves, and not license the software to industry for doing that and in effect competing with us."

Reify will, however, make the technology available to non-profit research institutions and universities in hopes of spreading word about the technology and building acceptance through scientific publication. Besides its work with Harvard's Liao, the company has also collaborated in the lab with Wilson Colucci, a member of Reify's scientific advisory board and professor of medicine and physiology at Boston University School of Medicine; and Calum MacRae, a professor and doctor at the Cardiovascular Research Center at Massachusetts General Hospital.

As for its plans to grow, the hiatus in seeking VC cash remains in place, but could change down the road, Walter said. In the near future, the company will attempt to grow via income from pharmaceutical research contracts, he said. Walter declined to comment on the pricing structure of the Myosite service.

— Ben Butkus ([email protected])

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