As high-content cellular analysis rapidly gains popularity as a drug-discovery tool, toolmakers have taken a decidedly sub-cellular approach to things.
Not everyone, however, is pursuing tthis approach. One such company is privately held Pittsburgh-based Automated Cell, which hopes its strategy of visual image detection at the whole-cell level will soon reap rewards.
Kevin Sullivan, vice president of business development at Automated Cell, told Inside Bioassays last week that the company is currently trying to market its cellular analysis technology in hopes of generating both short- and long-term revenues to further support the development of its own nascent antibody-based cancer therapeutics program.
“It literally is a complete instrument, and we have actually placed a couple [with] some of our academic collaborators,” Sullivan said. “There’s always been the possibility that we could spin out that instrument play. Right now we’re looking for a distributor for it … so I’m making all those phone calls to see if there’s someone interested in it as an instrument to sell into the life sciences research and development market.”
Sullivan declined to identify any possible suitors of the technology, but he did say that he has been in touch with GE Healthcare — although he gave no indication as to whether or not that company expressed interest.
Automated Cell’s technology caters to its “reverse” approach to drug discovery. Typically in drug discovery, scientists identify and validate a specific cellular target, then screen numerous compounds against it. Sub-cellular image-based analysis has allowed researchers to then examine how the cellular system as a whole reacts to target hits.
“Everyone’s chasing down pathway biology now pretty hard and heavy,” Sullivan said. “We don’t start with the target. We just start with an antibody library obtained from the plasma of cancer patients, find a functional antibody, and then back-track to find what target it hit.
“We’ve automated this and turned it into high-throughput assays,” he added. “We use those as our primary screen. When we get a hit, it’s a very functional hit. Then we go from there, with an antibody that has function against cancer.”
Automated Cell’s actual imaging platform is simple — light microscopy coupled with a CCD camera that captures images of cells in 384-well plates. “None of the image acquisition technology is too differentiated — it’s all [off-the-shelf],” Sullivan said. “I know our camera is really similar to the one that GE Healthcare’s [IN Cell] uses.”
According to Sullivan, visual analysis of the resulting images is where Automated Cell’s strength lies. Using software that the company licensed in 1998 from the University of Pittsburgh and Carnegie Mellon, a user can quantify 65 different phenotypic parameters of cellular biology, such as anchorage-independent growth, cellular proliferation, and cell-cell interactions — “the types of things that to everybody else in the field are secondary assays,” Sullivan said.
Sullivan said the software was originally developed by Joel Greenberger, assistant director at the University of Pittsburgh Cancer Institute, scientific founder of Automated Cell, and chairman of the company’s scientific advisory board.
“He’s a stem-cell researcher, and he wanted to be able to follow a living stem cell,” Sullivan said. “When it differentiated, he wanted to stain it right then and there to find out whether it differentiated or remained the same. So he had to have a means to watch a cell, track it, and then go in and stain it.”
Greenberger then collaborated with Carnegie Mellon to develop an instrument for that purpose, and while the same principles are intact, the platform “is all completely different now,” Sullivan said. “All the robotics and the software have been industrialized.”
Platform for Sale
Automated Cell has now turned its attention to finding a distributor for the platform while ushering its first lead compound into clinical studies. It announced its first antibody lead in October of last year — an antibody isolated from the plasma of Stage IV melanoma survivors that has subsequently shown efficacy in killing melanoma cells in vitro.
“We have a prime lead, and some hits behind it,” Sullivan said. “Tomorrow we could have the real thing, or it could be a year from now.”
Almost as important as the viable lead candidate, data from the melanoma studies has served to validate Automated Cell’s approach.
To this point, the company has not actually produced instruments for sale, but it has used the platform to generate income to support its melanoma research program.
“In a revenue-generating mode, we’ve screened other peoples’ libraries,” Sullivan said, “[Including] companies like AbGenix, Medarex, MedImmune, Oxford Glycosciences when they existed, MorphoChem. It would work for any library, whether it’s small molecules, antibodies, or proteins.
“The service model has never been our focus,” he added. “But when it gets tough, you’ve got to generate cash.”
Automated Cell is also currently trying to generate cash through VC funding. “We’ve had a series A, and we’re just now in the middle of trying to put together a series B,” Sullivan said.
The VC well for early-stage drug-discovery has dried up in recent years, but Automated Cell has garnered the support of local incubator Pittsburgh Life Sciences Greenhouse, in the form of a $100,000 investment late last year from PLSG affiliate Pittsburgh Biomedical Development Corporation.
Still, money has not been easy to come by, which is why the company seeks to outlicense its core technology and methods.
“We haven’t skyrocketed,” Sullivan said. “There were a couple of rough years in there, around 2001 and 2002, where we had a couple of good deals going, but then they went south when certain compounds went south.
“We know that there’s a very heavy fluorescence imaging market out there, but we’ve seen very little visual analysis, because it creates a lot of data and requires some pretty sophisticated IT,” he added. “But this does really exist as a complete instrument, and there’s quite a bit of firepower from an IT standpoint.”