VisEn Medical Inc.

VisEn Medical's core technology is based on activatable "smart imaging agents" and novel optical systems, including fluorescence-mediated tomography. The ability to visualize reactions and processes in vivo in real time using agents specifically activated by molecular targets, processes, or pathways-the molecular signatures of disease--may lead to breakthroughs that aren't possible with in vitro methods.

Imaging the molecular signatures of disease in vivo

12B Cabot Road

Woburn, MA 01801

Phone: [phone]

Fax: [phone]

Web Site: www.visenmedical.com

Contacts: Guy Mayer, Chairman and CEO; Kirtland Poss, President

Industry Segment: Molecular Imaging

Business: In vivo molecular imaging reagents and systems

Founded: June 2000

Founders: Kirtland Poss; Ralph Weissleder, MD, PhD

Employees: 22

Financing to Date: $15 million

The paper by Ralph Weissleder, MD, PhD, and colleagues in Nature Biotechnology in 1999 describing a method for using near-infrared (NIR) fluorescence probes to image tumor-associated protease activity in vivo in a mouse model quickly became one of the most recognizable publications in the nascent field of molecular imaging. Tagging NIR fluorochromes to peptide probes was a significant step toward making smaller imaging agents that could penetrate more deeply into tissue and provide visual and quantitative readouts.

Despite advances in PET, CT, and MRI in the '80s and ‘90s, these tools could not be used to visualize, characterize, and measure biological processes at the cellular and molecular level in vivo. Better imaging reagents were needed to reduce molecular imaging to practice: to enable early disease detection, characterization and treatment evaluation in the clinic; and as a drug development tool in R&D.

In contrast to conventional diagnostic imaging, which depicts anatomy, molecular imaging detects specific molecular activities and abnormalities that underlie a disease. It has its roots in in vitro diagnostics, where molecular biologists look for biochemical markers of disease. But the ability to visualize reactions and processes in vivo in real time using agents specifically activated by molecular targets, processes, or pathways—the molecular signatures of disease--may lead to breakthroughs that aren't possible with in vitro methods. (See "Imaging in its Heyday: Research Applications (Part 1)," START-UP, March 2002 (Also see "Imaging in its Heyday: Research Applications (Part 1)" - Medtech Insight, 1 Mar, 2002.).)

The director of the Center for Molecular Imaging Research (CMIR) of Massachusetts General Hospital (MGH) and Harvard University 's, Harvard Medical School , Weissleder had been developing molecular imaging technologies for a decade, including fluorescent approaches since 1997. "As a practicing clinical radiologist, Weissleder had been seeing disease morphology with conventional imaging modalities such as MRI and CT, but was frustrated by not being able to see what was actually happening with those diseases at the molecular level in patients," recalls Kirt Poss, who with Weissleder founded VisEn Medical Inc. Poss had worked in Weissleder's lab at CMIR. "He called me one day," Poss recalls, "and said in vivo molecular imaging was about to blossom, based on his technologies." Then a manager for Kendall Strategies providing strategic consulting to biomedical companies, Poss ran with the notion. He and Weissleder formed VisEn Medical in June 2000. VisEn's core technology, emanating from Weissleder's lab at CMIR and licensed from MGH, is based on activatable "smart imaging agents" and novel optical systems, including fluorescence-mediated tomography (FMT), which can sense small amounts of probe deep within tissues.

The blossoming that Weissleder envisioned didn't happen immediately, however. Armed with the 1999 Nature Biotechnology paper, they were able to raise seed capital. "But few people understood the value proposition, then," Poss says. The problem was that systems development and reagent development were not going on concurrently. "You need systems and complementary agents," Poss explains. "Without one side of the equation, the opportunity wasn't going to happen."

Expanding on his traditional focus on agents, Weissleder had begun to develop systems in his lab in the late '90s, including FMT. But systems companies weren't taking up the technology effectively enough to keep pace with VisEn's agent development. "We ended up licensing the FMT platform from MGH because we saw the need and opportunity to develop systems in-house, using a contract engineering firm, while the larger players were getting up to speed," Poss says. "Now, they have."

"Most of the leading imaging systems companies have had clinical optical imaging programs ongoing at some time in their past, but they have historically abandoned them because the resulting efficacy provided by the agents wasn't there," suggests Guy Mayer, VisEn's CEO. "The evolution of the right agents has spurred the focus and systems development activities at these companies again," Mayer says. "There are now several definable and significant R&D and clinical imaging opportunities within reach," he claims. Poss had talked to Mayer about VisEn while Mayer was CEO of Etex Corp., a Cambridge, MA-based developer of biomaterials. Mayer became an angel investor in VisEn and its chairman, and moved into the CEO role a year-and-a-half ago.

Although VisEn initially saw itself focusing solely on agents (probes), it needed systems with which to demonstrate and apply the power of the imaging agents. The start-up ended up spending much time in its first few years refining and broadening the FMT technology base internally, as well as building additional corporate and academic relationships. VisEn also continued to build its IP estate by licensing complementary technology for systems and probes from MGH and other institutions. Now, VisEn's small animal imaging system, which has been in alpha development since the middle of 2003, is in beta sites at Novartis AG and at MGH, with two more pharma companies expected to join, according to the company. VisEn is also finalizing an agreement with an OEM for a commercial unit, which it expects to make available in the third quarter of 2004.

"When we founded VisEn, we saw the enabling technology as being in probes for optical imaging," says Poss. "We still do. But in the first year, we also saw the need for the right system—tomography." Other types of systems are planar—light shines in one direction, like an X-ray. FMT, however, is like a CT scan, he explains, enabling deeper imaging in tissue, and providing quantifiable data from point sources in patients. "Our probes will work with essentially all optical imaging system approaches, but we see the performance of FMT as enabling at a higher level," says Poss.

While the company's bet on the systems side is with FMT, it is developing several flavors of agents: both activatable (by a disease process) and targeted probes, which may be used with multiple platforms including tomography, reflectance, and time domain, and different signal amplification methods. VisEn is also developing targeted MR probes that will be used independently and in conjunction with the optical probes in dual-modality imaging applications. Generally, these probes comprise a delivery vehicle (a biological backbone), a binding (targeting) or activatable component, and a reporter mechanism that varies depending on the modality and manner of signal amplification: fluorescent activation, magnetic targeting, multivalency, cellular trapping, or enzymatic conversion.

"With our probes, we can image molecular activity to determine the onset of the transition from healthy to diseased tissue, or later on, the amount of disease present or patients' response to inhibitors," says Poss. VisEn's first family of probes is for sensing protease activity, which is associated with cancer, inflammation, and atherosclerosis, in animals. Protease activity increases midway between the initial threshold of disease and morphological change, notes Poss. "It's a downstream marker for disease," he says, "but is earlier than standard metrics of disease progression."

VisEn is also developing probes for the gelatinase family of enzymes, which are activated by matrix metalloproteinases and are implicated in cancer, arthritis, and asthma, as well as a group of nonactivatable vascular probes to image or quantify angiogenesis and inflammation. According to Poss, the latter two groups of probes will also enable earlier imaging of disease. VisEn expects to release probes in each of the three categories in the second half of 2004 for research purposes; it also expects to select its first clinical molecular imaging probe candidate by the end of this year, with a timeline for an IND at the end of 2004.

While VisEn sees the animal imaging market as an attractive opportunity to develop both its technologies and its business, the start-up sees its end game being the clinical introduction of its probes in patients, and VisEn is refining its lead candidate now. "Importantly, these technologies were developed by a clinical radiologist, for the clinic. We have defined clinical development programs under way now and should be in patients with our lead candidate in the first half of 2005," says Guy Mayer.

The start-up is rounding out its core competencies in R&D, and will soon expand its hires in manufacturing, Mayer says. In another 12 months, the company should grow to around 40 people. VisEn is also starting the fund-raising process for a Series C round, expected to close in the first half of next year. (Siemens AG 's Siemens Medical Solutions made an equity investment in VisEn in 2003.)

CEO Guy Mayer was formerly president and CEO of biomaterials developer, Etex Corp. Before that, he held various senior positions at Zimmer Inc. VP, R&D, Dean Falb, PhD, was formerly VP, drug discovery, at NeoGenesis Pharmaceuticals Inc. Falb was also SVP, research, at Praecis Pharmaceuticals Inc. and before that, a founding scientist at Millennium Pharmaceuticals Inc.—MLR