Theraclone Sciences has taken its first step ahead toward showing it might have an antibody drug that could work in humans.
The Seattle-based biotech company is announcing today that it passed its first clinical trial with an antibody drug designed to fight a wide variety of flu strains. The study randomly assigned 40 healthy volunteers to get a dose of Theraclone’s TCN-032 or a placebo. Researchers found that the treatment was safe and well-tolerated at all five doses studied, didn’t appear to cause any serious side effects, and didn’t provoke an immune reaction against the drug.
“This study exceeded our expectations,” says Leni Ramos, Theraclone’s chief medical officer.
Theraclone plans to release more detailed results at a future scientific meeting, which will include strategically important information on how long the drug lasts in the bloodstream. And today’s study results don’t say anything about whether the drug is effective at killing flu viruses in human beings. But the results are promising enough that the company plans to take the next step in clinical trials, advancing to a mid-stage clinical trial later this year in which the drug will be tested among people who get exposed to flu virus in a carefully controlled environment. That study will be placebo-controlled, and is being designed as the first to establish biological proof in humans that TCN-032 can effectively kill the virus, Ramos says.
While there are already a couple of antiviral pills on the market—Roche’s oseltamivir phosphate (Tamiflu) or GlaxoSmithKline’s zanamivir (Relenza)—scientists worry about mutant strains like H5N1 “bird flu” that could emerge and resist today’s antivirals. Even without some mutant supervirus in the air, an estimated 200,000 people are hospitalized in the U.S. each year with flu, and 36,000 people in the U.S. still die from annually. Most are elderly, young children, or those with weakened immune systems.
Theraclone, founded in 2005, has spent years working to get to this point by developing its technology for discovering “broad-neutralizing” antibodies. Theraclone has shown in the lab that it can find antibodies that can fight a wide variety of infectious invaders, from HIV to flu to cytomegalovirus (CMV). Japan-based Zenyaku Kogyo helped finance the anti-flu antibody work, and it retains commercial rights to the Theraclone product candidate in Japan. Zenyaku remains committed to support further development, Theraclone CEO Cliff Stocks says.
Exactly how such a flu antibody might be used, in practical terms, is still an open question. Since Theraclone’s antibody is given intravenously, it’s not the kind of flu-fighting product people will ever get at their neighborhood Safeway. But it could be valuable to hospitals looking to have a potent anti-flu weapon on reserve for tough cases, and for public health officials, who may want to stockpile it in case a particularly nasty pandemic flu strain emerges.
Theraclone isn’t the only company out there with visions of creating a potent antibody drug against flu. Netherlands-based Crucell, acquired last year for $2.3 billion by Johnson & Johnson, has said it is working on a “universal antibody” for flu. It has said that its antibody candidate is designed to hit the hemagglutinin protein that appears on various flu viruses.
Theraclone’s program is different in a few key respects, Stocks says. For starters, Theraclone believes it is ahead in development, since the Crucell program is thought to still be in preclinical development. Second, the Theraclone antibody is made to hit a different target on flu viruses, known as matrix 2 protein (M2e). That distinction is important because an estimated 98 percent of flu strains contain the M2e region in their DNA. Viruses can easily mutate when confronted with a powerful new drug that threatens their survival, but Ramos says if flu viruses mutate away from the assault of Theraclone’s TCN-032, then they would lose their ability to be infectious.
The next study will say a lot about whether Theraclone has a real drug it will be able to sell, and it won’t have to wait eons for the answer. The next study will be based on volunteers getting a single dose, and since the antibody is designed to last several weeks in the bloodstream, it won’t need to be given in repeat doses over time to prove it’s effective against the virus, Ramos says.
