|Against all odds
By Martha Nolan McKenzie • Illustration by James Soukup
For every Emtriva, however, there are countless other products that never make it to market, much less strike it big. Some, after years of development and testing, fall short in a late-stage clinical trial. Some, despite true promise in animal trials, fail to rise above the din and attract a venture capitalist’s attention. Some aren’t identified as important early enough in process and so fail to get a patent.
“Only about 1% of the products being researched will be a big hit financially,” says Todd Sherer, director of Emory’s Office of Technology Transfer.
To be in that 1% takes a good product, years of hard work and, more often than not, luck.
The daunting odds of success have a lot to do with the nature of university research. Unlike corporations, which will fund only research that has a high likelihood of paying off, university research is fueled by scientists’ curiosity. “We are pursuing knowledge for knowledge’s sake,” says Sherer. “That kind of research will lead to more revolutionary discoveries. But it also carries a higher risk of never panning out.”
The Office of Technology Transfer identifies products and procedures that have real potential and then helps them get through the tangle of regulatory and legal processes that precede a market debut.
“It’s a wonder anything gets to market,” says Sherer. “There is a lot of technology and innovation pooling up behind the dam—only a tiny bit trickles out to the marketplace. A lot of excellent research never sees the light of day.”
|Stacking the AIDS deck
GeoVax is one Emory start-up that is hoping to beat the odds. The company has developed a vaccine to prevent HIV/AIDS that is currently in phase 1 clinical trials in humans. Results have proven so promising that GeoVax plans to begin phase 2 trials this summer—about a year ahead of schedule.
The vaccine involves a two-part regimen. First, the patient receives a DNA vaccine, which primes the body’s immune response. A few weeks later, the patient receives a different type of vaccine, a modified vaccinia Ankara (or MVA), to boost the original immune response. Neither contains the “live” virus and therefore cannot cause a patient to develop HIV, according to Emory immunologist Harriet Robinson, one of the scientists to discover DNA vaccines in the 1990s and chief scientific officer at GeoVax.
The GeoVax team first tested the vaccine in rhesus monkeys, with better than expected results. “We protected 22 out of 23 nonhuman primates for almost four years after they were exposed to the virus,” says Don Hildebrand, GeoVax CEO. “By contrast, 5 out of 6 monkeys who were not vaccinated died within a year.”
In the first human trial, the vaccine has boosted T cell and antibody responses at just one-tenth the optimal dose. Researchers have seen very good responses in 80% of the volunteers who received the full dose, says Robinson. The vaccine also has proven safe, she says, with participants reporting no problems or side effects.
Buoyed by these results, GeoVax has started planning therapeutic trials to vaccinate people already infected with AIDS but who remain relatively healthy, with intact immune systems. In preclinical trials with HIV-infected monkeys, the animals responded so well to the vaccine that they no longer needed anti-retroviral drug treatment. Treatment with a vaccine rather than with complicated, life-long drug regimens also has great potential to reduce costs and side-effects, according to Robinson.
“If this vaccine works, it will break the epidemic,” she says. “A vaccine that is only 30% effective could begin to break an epidemic, and we certainly hope ours would do better than that.”
|Betting on a cure
The odds of winning in the tech transfer game can improve substantially with the right name. Just ask Pharmasset. In 2004, the six-year-old Emory biotech start-up was able to secure funding largely on the strength of the reputation of its founder, Raymond Schinazi.
Today, Pharmasset is a publicly traded company residing in Princeton, N.J., and Schinazi is no longer directly involved with its operations. “It’s sort of like having a child,” he says. “It has grown up and left the nest.”
The company now has several promising products in its pipeline. One of these drugs, Clevudine, an oral medication for hepatitis B, is in advanced clinical trials in the United States and already is in use in Korea. Studies have shown that Clevudine brings virus levels down and keeps them down—important especially in Asia where hepatitis B is endemic and in the United States, as well, with more than 1 million people infected.
“It has the potential for curing hepatits B infections,” says Schinazi.
Next in Pharmasset’s arsenal is Racivir, a treatment for a resistant strain of HIV. “Racivir is potentially a ‘me-better’ as opposed to a ‘me-too’ HIV drug,” says Schinazi. “It works against a viral mutation of HIV that is found in the majority of patients, and it has been shown to be safe.”
A particular attribute of Racivir is its low manufacturing cost. “That has huge implications in Africa, where they’ve historically been worried about the cost of treatments and somewhat less about their effectiveness,” sasy Schinazi. “If we can provide an effective, low-cost drug, the impact will be amazing.”
Pharmasset’s “crown jewel,” according to Schinazi, is R7128, a treatment for hepatitis C, the leading cause of liver disease. More than 170 million people are infected with hepatitis C worldwide, as are 3% of Americans. In the United States, many patients have a form of the virus that does not respond to current treatments. In phase 2 clinical trials, R7128 reduced the virus to undetectable levels in an astonishing 85% of patients after only four weeks of treatment.
“R7128 is an H-bomb for the hepatitis C virus but essentially harmless for the host,” says Schinazi. “We are talking about a potential cure for hepatitis C here. This could have a huge global impact.”
|Spinning the wheel for stroke
NeurOp, a six-year-old Emory biotech start-up, is developing a novel treatment for stroke victims that could dramatically curtail the devastating effects of stroke. Whether patients will ever get a chance to benefit from the product will depend on whether the company can convince investors of its promise.
“We are at that delicate stage of small company development where we have a proof of concept in animal models that our strategy is sound and should work,” says Emory pharmacologist Raymond Dingledine. “We now need to raise enough money to actually bring the whole thing home. We’re talking with several pharmaceutical companies and venture capital firms, but the clock is ticking. Small companies can’t survive forever,” says Dingledine, who co-founded NeurOp.
The drugs NeurOp is developing target a protein in the brain that is responsible for one-third to one-half of the brain damage suffered by stroke victims. Blocking that protein can prevent the damage from occurring. But there’s a problem: the same protein is necessary for normal function in the other healthy parts of the brain. Blocking it can lead to mental clouding, cognitive impairment, hallucinations, and lack of coordination.
That’s where NeurOp’s approach is so unusual. Dingledine and Emory pharmacologist and NeurOp co-founder Steven Traynelis have developed a drug that blocks the protein in the damaged part of the brain but leaves it alone in the healthy parts. That’s because the drug’s action is magnified in an acidic environment. And when a person suffers a stroke, blood supply to part of the brain is cut off. The metabolism in that section switches from aerobic to anaerobic, and the tissue begins to make lactic acid and other acid metabolites, just as muscles do during a heavy workout. As a result, Dingledine and Traynelis are able to administer a dose so low that healthy regions of the brain are unaffected, but the damaged, acidic regions of the brain receive the drug action.
“This product could fill an enormous, unmet medical need,” says Dingledine. “Right now the only therapy for stroke is tPA, a clot-busting drug, but it is administered only to 2% of stroke patients. It has to be given immediately—within a few hours of the stroke—to do any good. Also, if it’s a stroke caused by bleeding in the brain, it makes the bleeding worse. So doctors have to determine the type of stroke—blockage or bleeding—before they can give tPA. Our drug could be given by paramedics to any stroke victim on the way to the hospital.”
The ante for safer blood
Editor’s note: These faculty members and Emory University have equity interests in the companies described. They may receive royalties on the technologies being studied, and some may have paid consulting relationships.