Scientists have been trying for years to solve the mystery of why a few rare individuals get infected with HIV, yet somehow retain immune defenses so they never get sick. Today, researchers at a small Seattle biotech company, Theraclone Sciences, and collaborators at San Diego’s Scripps Research Institute say they have found a new vulnerability in the virus that could lead the way to new treatments or possibly a vaccine.
By studying rare blood samples from HIV-resistant people in the lab, scientists have found two weak spots on the virus, and were able to genetically engineer two new antibodies that broadly neutralize many variations of the virus circulating around the world, according to research being published this week in Science. Besides Theraclone and Scripps researcher Dennis Burton, this effort included collaborators from South San Francisco-based Monogram Biosciences (NASDAQ: MGRM) and the International AIDS Vaccine Initiative (IAVI) in New York.
This effort is still in its early days, and nobody knows yet for sure if these new antibodies will even work in lab animals. But this is the first time in more than a decade that scientists have discovered antibodies with broad neutralizing capability that can stand up to multiple strains of the wily virus in the lab. Plus, they were found in blood samples from donors in developing countries, where most of the new infections occur.
While HIV is largely considered a chronic disease in wealthy countries like the U.S. where there are 32 FDA-approved antiviral drugs, the discovery of neutralizing antibodies is potentially groundbreaking. The antibodies could be critical ingredients used to develop the first HIV vaccine, which would be most useful in poor countries. More than 30 million people around the world are thought to be living with HIV, and the disease is still thought to kill 2 million people a year.
“These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design,” said Burton, a professor of immunology and microbial science and scientific director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, CA, in a statement. Burton is also a member of the newly-formed Ragon Institute, a collaboration of Massachusetts General Hospital, MIT, and Harvard.
We first wrote about this HIV work in April based on an interview with Theraclone CEO David Fanning. I caught up with Fanning again by phone to talk about the business implications of getting such big recognition in one of the world’s top two scientific journals.
This publication—and all the global media attention it is bound to attract—is definitely going to attract the interest of prospective partners in Big Pharma and biotech, and funding agencies like the National Institutes of Health, that Theraclone needs to help pay the bills for its research program. When Fanning called me, it was 4 a.m. in Japan, where he has been meeting with potential partners. “I’m not here for vacation, you can put it that way,” he says.
“This really validates our technology in the eyes of people that we want to see start using it,” Fanning says. “Instead of us being a small private biotech that may or may not be doing something interesting, we’ve now made a mark very rapidly in one of the biggest challenges of all infectious disease.”
Still, the work is clearly just beginning. Theraclone, through ongoing financial support from IAVI, is looking to build on this discovery by running experiments to see if the broadly-neutralizing antibodies can have anti-viral activity in mice. Theraclone owns the intellectual property to turn these antibodies, called PG9 and PG16, into treatments for chronic HIV infection. IAVI owns the rights to use them to create vaccines, Fanning says. So even if while the venture capital crowd may not be interested in financing an AIDS vaccine business, the public health crowd certainly is.
In short, the vaccine work has global implications. Yet if Theraclone wants to truly move forward with an antibody-based treatment for HIV, it will certainly be an uphill battle. Various cocktails of antivirals have already basically turned HIV in wealthy countries from a death sentence into a chronic disease to be managed. The drugs have made fortunes for companies like Gilead Sciences and GlaxoSmithKline, and they are much cheaper to manufacture than an antibody.
But one drawback is these pills need to be taken diligently every day, as Fanning pointed out when we talked in April. Patients, some of whom are indigent or drug users, sometimes struggle to stick with this disciplined medication schedule for life. In doing this, they run the risk of letting the virus develop resistance to these treatments. So Theraclone hopes there’s room in the market for a genetically engineered drug that could be given intravenously under a doctor’s supervision once a month, or maybe even less frequently.
But more importantly, as Fanning said, this provides some high-profile evidence that Theraclone’s approach of looking for unusual antibodies produced by Mother Nature can have broader implications against infections beyond HIV. The company’s lead product candidate is an antibody that’s thought to have this same kind of sweeping potential against multiple strains of flu virus, which could come in handy in the case of a bird flu, swine flu, or some other kind of flu pandemic. Theraclone has some “compelling” data that this antibody can protect mice from a deadly strain of H5N1 “bird” flu, and this is the program generating much of the interest of potential partners, Fanning says.
The third Theraclone program is to make antibodies against cytomegalovirus (CMV) which doesn’t usually harm people, but can be life-threatening in people with weakened immune systems, like the elderly or people undergoing cancer chemotherapy.
While the folks at New York-based IAVI are sure to get a lot of attention, and Burton is sure to get a lot of the press attention, there are six named authors from Theraclone on the paper being published in Science. They are: Po-Ying Chan-Hui, Jennifer Mitcham, Steven Frey, Phillip Hammond, Ole Olson, and Matthew Moyle. Theraclone only has 21 employees, 18 of whom are scientists, and “about 80 percent” of them spent much of a six-month period on the antibody discovery effort for HIV in the past year, Fanning says. The work, and recognition of it, has certainly had a good effect on morale in what is otherwise a pretty difficult environment for a company trying to do some high-risk, high-reward science.
“This is a really big deal for us scientifically,” Fanning says. “For years, the question was whether these broadly neutralizing antibodies even exist. Now we know they exist, and we need to do more work to identify more of them. We really hope this will be the beginning of a flow of valuable antibodies against the virus.”
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