Imagine spotting the pathology of a disease - say, the amyloid plaques characteristic of Alzheimer's or the death of pancreatic beta cells in diabetes - when it first appears, long before clinical symptoms occur. That's the vision that Daniel Skovronsky, president and CEO of Avid Radiopharmaceuticals, wants to make a reality.
Instead of parsing memory test scores to identify a patient with early Alzheimer's disease or measuring blood glucose levels in people at risk of diabetes, the 34-year-old Skovronsky explains, the technology would allow clinicians to observe the "fundamental pathology" of the illness in its early stages, with the ultimate goal of treating patients very early in the course of a disease. The technology could also be used to measure the progress of disease treatment.
Skovronsky launched Avid in 2004, using borrowed office space and financing many early expenses on his personal credit cards. Today the Philadelphia-based company has raised $35 million and expanded its lab space footprint four times. Investors including Pfizer and Eli Lilly have signed on, and Avid is now collaborating with a dozen academic partners, designing and managing its own clinical trials, and running a manufacturing facility to supply drugs for several Phase I clinical trials currently underway. The local business community is taking notice; the Philadelphia Business Journal named Skovronsky one of its "40 under 40" business leaders in 2006.
Franz Hefti came on as Avid's vice president of neuroscience after leading drug development at Rinat Neuroscience Corp. (which Pfizer acquired in 2006 for $500 million, the largest sum ever paid for an early-stage biotech company). He calls his new job "one of the most exciting opportunities in current biotech."
Avid's earliest days were a "juggling act" that required Skovronsky to secure intellectual property, raise money, and find good people, all at once. "All three of these things kind of hinged on each other," he recalls. While he launched the company in late 2004, he held on to his day job as scientific director of high-throughput screening and drug discovery at the University of Pennsylvania's Center for Neurodegenerative Disease until July 2005.
"It's been challenging along the way, but I've enjoyed the challenges. That's what makes it fun," he says. "You have an idea and a vision. You have to communicate that to others."
Skovronsky's ability to speak about his vision for the company impressed funders, as well as the number of high-level, seasoned scientists and managers like Hefti who have since joined Avid. "He was able to very clearly articulate not only the science, but the mission," recalls Gary Kurtzman, who provided seed money to the company while at BioAdvance, a biotech greenhouse serving southeastern Pennsylvania. Now at Safeguard Scientifics, a holding company based in Wayne, Pa., which invests in life science companies, Kurtzman participated in Series C funding of Avid as well. "I fully expect that he'll make this successful, and that he'll make whatever comes next successful," Kurtzman adds. "He was at that time a 32-year-old CEO and he was doing a great job of it, and he's only gotten better."
Skovronsky graduated from Yale with a degree in molecular biochemistry and biophysics. He went on to get his MD and PhD from the University of Pennsylvania, and completed his residency in pathology and a fellowship in neuropathology at the Hospital of the University of Pennsylvania. While at Penn, Skovronsky and radiochemist Hank Kung developed the technology on which Avid's products are based. Kung is now chief scientific advisor of Avid and chairs the company's scientific board.
"The technology comes from the idea that we should be imaging amyloid plaques," Skovronsky explains. "You can't just see them like bones on an X-ray. They're too small, there's no contrast." He and Kung began with fluorescent dyes used in neuropathology, modifying them to make drugs that could be injected into patients and would "light up" the relevant lesions with radioactivity that could be seen on a positron emission tomography (PET) scan.
"It took thousands and thousands of compounds that initially were derivative of dyes but got structurally further and further away from those dyes," Skovronsky says. They were looking for compounds with avidity and specificity--hence the company's name. "In each case we're inspired by the pathology, what does the pathologist see under the microscope."
The most challenging aspect of the science, he adds, has been "developing a compound with all the right properties for brain imaging. It's a delicate balance between brain entry, rapid clearance, and high-affinity binding to the target."
Avid is focusing on four disease areas: Alzheimer, using compounds that bind to amyloid plaques; Parkinson disease and dementia with Lewy bodies, targeting VMAT2, a marker of healthy dopaminergic neurons; and diabetes, again targeting VMAT2, which is also expressed on the pancreas' beta cells. During the course of their research, Skovronsky and his team made the "fortuitous discovery" that the brain and beta cells expressed the same protein.
The Alzheimer-targeting compounds can be used with Single-photon emission computed tomography as well as PET, notes Skovronsky, which will make the technology cheaper and more widely available.
Skovronsky's current goal is to begin Phase II trials in at least two if its programs. Avid is in competition with a team at the University of Pittsburgh, which is working on bringing similar technology to market in collaboration with GE Healthcare.
For Hefti, Skovronsky is a shining example of an MD/PhD - exactly what the educational system was looking for when it launched these programs several years ago with the goal of creating physician scientists. His entrepreneurial skills also are impressive, adds Hefti. "He's a well-rounded young person. The only thing which is lacking is essentially experience."
One challenge for the company has been to convince funders that a diagnostic tool can actually make money, Hefti points out. "Most people have this core belief that there is no money in diagnostics. There is a bit of a negative reflex there [that] one has to overcome." However, he adds, "here is a company that says we can visualize whether somebody has, for example, Alzheimer's disease, and people will pay for that, to know that, and the reimbursement agency will reimburse the procedures, and the HMOs will pay for the procedures, and there is significant money there. It's a new business model that people have to get familiar with."
Skovronsky says he thrives on the responsibility that comes with leading a company after academia, where "there's a little bit less personal accountability. In business, particularly in my role, you have to have a buck-stops-here mentality. It generates a fair amount of pressure."