Prevnar 13 is a vaccine that, as its name suggests, protects against 13 of the most common strains of pneumococcal bacteria, which can cause deadly pneumonia and meningitis infections. There’s just one problem: there are around 90 total strains of pneumococcus that can cause disease. What about the other ones?
A new startup with backing by the Bill & Melinda Gates Foundation called Affinivax claims it’s created a vaccine to protect against all 90. Now comes the hard part: scaling up, proving it in clinical trials, and making a successful business out of it.
Cambridge, MA-based Affinivax today is emerging from stealth with $4 million in seed cash from the Gates Foundation, which has increased its investments in early-stage biotechs tackling world health problems over the past few years.
The Gates investment includes future payments triggered if Affinivax hits certain predefined development milestones for its vaccine platform.
Steven Brugger, Affinivax’s CEO—formerly of Cambridge infectious disease startup Visterra, and Momenta Pharmaceuticals (NASDAQ: MNTA) and Millennium Pharmaceuticals before that—wouldn’t say how much more money the Gates Foundation has committed. But its support will help Affinivax advance a pneumococcus vaccine it’s developing towards its first clinical trial.
Affinivax has recruited big vaccine names for the effort. Its scientific founder is Richard Malley (pictured above, right, with Brugger), an infectious disease expert at Boston Children’s Hospital who has worked with non-profit organizations like PATH and the Gates Foundation, both based in Seattle, for more than a decade.
Former Wyeth Vaccines president and chief scientific officer George Siber is Affinivax’s lead scientific advisor. Siber and Malley are joined on Affinivax’s board by the Gates Foundation’s Bob More (a former VC at Frazier Healthcare Ventures) and Amit Srivastava, and by former Bristol-Myers Squibb senior VP of business development Frances Heller.
Gates Foundation is a non-traditional backer for a startup like Affinivax, but their missions align. The foundation aims to tackle some of the world’s biggest health problems, including a dearth of effective vaccines in the developing world.
Affinivax, being spun out of Malley’s work at BCH, is building a platform to quickly and cheaply develop vaccines that not only provoke a broader, more protective immune response than typical vaccines, but combat infections for which there are no effective vaccines today.
The problem is that vaccines are expensive and complex to manufacture and test in clinical trials. This not only makes them exceedingly difficult for startup biotechs to develop, but, Malley notes, limits their reach to the developing world. For a typhoid vaccine, for instance, the typhoid is grown, killed, and injected into the body, giving the immune system a test case should a live version of that pathogen ever invade in the future.
The problem with that approach, says Malley, is that it’s “ill-defined.” Childrens’ immune systems are immature compared to adults. They often don’t recognize certain antigens—substances that provoke an immune response—and that can render some vaccines useless. To combat this, some vaccine technology now magnifies those antigens, so to speak, for the immune system.
One magnification approach is known as a conjugated vaccine. This is when an antigen (a polysaccharide or “sugar coat” of a bacteria, Malley says) is bonded to a protein that carries it along and helps boost the immune response to that antigen. Prevnar 13 is an example of such a vaccine.
Malley says, however, that the conjugate approach is limited in a few ways. First, only so many sugar coats are typically tied to a protein, which limits the amount of bacterial strains the vaccine can protect against. This gives other strains that aren’t affected the chance to rise up. Second, the protein carrying these sugars doesn’t usually generate immune responses of its own, Malley says. It’s also a costly, difficult, time-consuming process to form conjugate vaccines, he adds.
“You have to have a very deep knowledge of how not to damage the polysaccharide in the process of physically attaching it to something else,” Malley says. “You’re chemically reforming bonds between two things, which requires a very deep knowledge of what you could be damaging in that process.”
Affinivax says its core technology can overcome these limitations and create vaccines more quickly than the norm. Through its own chemistry process, it tags a protein and sugars with two substances that have high affinity for one another—biotin and rhizavidin. Affinivax calls these “affinity” tags (hence the company name), because when everything’s mixed in a solution, the protein and sugars immediately find each other and stick together “like Velcro,” Brugger says.
Affinivax also uses proteins that are found across different strains of bacteria that it’s interested in—for instance, the 90-plus strains of pneumococcus—as part of that process. Malley claims this leads to a two-pronged immune response: antibodies to sugars, and T-cells to proteins.
Affinivax believes this approach will provide broader protection against more strains of bacterial infections, a more significant immune response than current methods, and the ability to tackle complex bacterial infections that don’t have effective treatments.
Further, Malley says the tagging process is quick; it’s an interaction “that is automatic and doesn’t require any human intervention.”
That’s particularly important as Affinivax tries to scale up. Cost of goods in vaccine development is high but the price companies can charge for vaccines is low compared to many other drugs. Those factors, and the long clinical development timelines, make it much more difficult to build a business and generate returns for investors.
Affinivax is trying to buck the trend. It hasn’t proven the claims about its technology in humans yet, but with Gates’s help, the company’s pneumococcus vaccine could become a “showcase” for its technology. It’ll try to build from there.
“The vaccine space has been challenging,” Brugger says. “My hope is that when you look at a technology like [ours], it’ll put back on the radar the fact that there are ways to discover and deliver these types of vaccines that can be cost effective, that can be profitable, [and] that can meet the needs of the developing world. It can be done.”