Trimeris Is Born
In late 1992, Jesse Treu, a general partner of venture capital firm Domain Associates L.L.C. in Princeton, N.J., stopped by the Duke University lab to visit Bolognesi, a member of the scientific board of advisers of one of Domains portfolio companies. Treu heard all about the animal results with T-20.
I was excited. I envisioned a company not with solely an AIDS focus, but with an anti-viral focus, Treu recalls. Domain Associates led the financing effort, and in February 1993, Trimeris was born. We started the company with no staff, from scratch, around a scientific idea, Treu adds. The Duke foundersBolognesi, Matthews, and Max Wallace of the Duke investment officecreated the company name. It reflects their love for the seamer for sea, and tri for North Carolinas Research Triangle Park. The logo design combines a Nautilus with the pitchfork carried by the Duke Blue Devil mascot.
Bolognesi and Treu didnt realize that they had Rensselaer in common until they began chatting on the day they met in 1992. And they found that their careers had followed similar paths. After Rensselaer, Treu earned his doctorate in physics from Princeton, but he worked on a biological problem, cooperative binding of oxygen to hemoglobin. Meanwhile, Bolognesi segued from physics to earning his Ph.D. in virology at Duke, where he maintained a large research group until he left to join Trimeris two years ago. I switched to biology because I wasnt doing so well in physics, he says. Virology quickly captured his attention. A seminal point was meeting and working with Dwight Wilson. He opened my eyes to virology and its potential. At RPI I studied Newcastle disease, which is a flu-like illness in chickens, Bolognesi adds.
| Pursuing T-20 is fulfilling a long-held dream of Bolognesis to treat viral disease.
Being here at a very key moment in the AIDS crisis, with a potential new drug that acts by a new mechanism that can really help a growing number of patients with limited options, is a very exciting opportunity. To carry it to other pathogenic viruses associated with medically important diseases is our next challenge.
After Princeton, Jesse Treu went to General Electrics Corporate Research and Development Center in Schenectady, N.Y., where he joined an eclectic and stellar group of scientists who were exploring many interdisciplinary research areas. At GE Treu collaborated with Ivar Giaever 64, currently Institute Professor of Science at Rensselaer and winner of the 1973 Nobel Prize in physics. Treu soon began to look beyond the science to the business side of his work. I saw the technology transfer aspects of research, and became enamored with the commercial process. So I asked for a chance to move into management, he recalls.
Treu became a liaison between the research center and businesses, matching technology to real-world commercial problems. I put together teams, got funding, and told business managers what was going on in their labs, he recalls. Treu also was one of the first to spotlight the potential medical applications of magnetic resonance imaging (MRI) technology. He left GE in 1977 to head a research and development team at Technicon Corp. in Tarrytown, N.Y., overseeing development of blood chemistry and antibody tests. From there he moved to a venture capital firm in New York City. He became a co-founder of Domain Associates in 1985, now one of the largest venture capital firms in the United States focused exclusively on the health-care business.
The connection between Bolognesi and Lipton goes back to their days at Rensselaer, where they played on the varsity baseball team. Dani and I were very close friends at RPI, recalls Lipton, who was an outfielder and a first baseman. He was one of the best pitchers on the team, and I was his personal coach. They dont play a lot of baseball in Italy, where he grew up. He had the physical stuff down, but someone had to teach him how to play the game. Bolognesi says of Lipton, Jeff was one of the high-caliber politicians on campus, involved in student government. I was more into sports.
Lipton entered the business world earlier in his career than did his fellow alumni, heading for Harvard Business School and then a 29-year career at DuPont, where he was vice president for diagnostics. While at DuPont, Lipton collaborated with his baseball protégé in developing the first diagnostic test for HIV infection, among other projects. He left DuPont in 1993 to become president of Nova Corp. in Calgary, Canada, and became CEO when Nova Chemicals split from the parent company.
While I was with DuPont, I helped Dani develop the original contract between himself and Duke as plans were under way to commercialize the discovery, says Lipton. I guess I was Danis personal coach again, this time to help him form Trimeris. A few years later Lipton got a call from Bolognesi. The company was being funded principally by Domain and required more capital to move T-20 ahead in clinical testing. So in 1995, Lipton put together a group of investors and they got Trimeris over the hurdle. Then I slowly became more involved and joined the board, recalls Lipton. When Treu resigned as chairman of the board, Lipton took his place.
Clinical Trials Begin
Progress was rapid following the founding of the company. T-20 received a patent on Oct. 23, 1995. A few months later, the researchers showed that it vanquished HIV in mice whose own immune systems had been destroyed and replaced with a human immune system.
Phase I/II clinical trials for safety and efficacy proceeded at the University of Alabama at Birmingham, and the team published exciting results in the November 1998 issue of Nature Medicine. T-20 was safely dosed in all patients with no serious toxicities, said Michael Kilby, the principal investigator at the University of Alabama. We were pleased to find that patients in the highest dose group experienced profound reductions of viral load, even though T-20 was the only anti-HIV drug they were receiving, he adds.
Trimeris president and CEO M. Ross Johnson said at the time, At the highest dose tested, T-20 reduced the amount of virus in blood by almost 99 percent within two weeks. Its short-term potency was comparable to the best current drugs, and it was well-tolerated.
The success story continued in 1999. T-20 and a T-20 cousin, T-1249, received FDA Fast Track status, and Trimeris officially teamed with Hoffmann-LaRoche to commercialize both drugs. A 48-week clinical trial conducted by Trimeris researchers showed impressive results. The trial involved 70 patients who had experienced an average of 10 drugs and had signs of advanced disease. As a component of a combination regimen, T-20 cut HIV levels by 10-fold, or to below the detection level, in 23 patients. Of the 41 patients who completed the 48 weeks on the trial, 56 percent responded, for a 33 percent overall success rate astounding, considering how sick the patients were. Almost as important, participants reported that using T-20, which must be administered in twice-daily injections, did not disrupt their daily routines. Larger-scale phase III trials, involving more than 1,000 patients at 58 centers in Europe, Australia, and North and South America, are now under way. The company plans to submit final clinical trial results to the FDA in the early second half of 2002.
Pursuing T-20 is fulfilling a long-held dream of Bolognesis to treat viral disease. Being here at a very key moment in the AIDS crisis, with a potential new drug that acts by a new mechanism that can really help a growing number of patients with limited options, is a very exciting opportunity, he says. To carry it to other pathogenic viruses associated with medically important diseases is our next challenge.
Ricki Lewis is the author of Human Genetics: Concepts and Applications, in its fourth edition (McGraw-Hill Higher Education, 2001), and other textbooks. She is a contributing editor to The Scientist. She has a Ph.D. in genetics.