Do you hate needles? The flu shots of the future could be skin patches delivered to your doorstep.

It’s a pivotal moment for the nearly 11-year-old startup, which was founded by Harvard Business School students and based on science from Tufts University and MIT. If the trial goes well, Vaxess could earn an additional $10 million from its current investors and will begin seeking more funds for larger trials of its technology.

Success would also bode well for other startups and university labs developing their own skin vaccines. These experimental vaccines replace one large needle with dozens of tiny ones. These micro-needles are just long enough to slip the vaccine under the surface of the skin, but are too short to prick nerves.

Vaxess chief executive Michael Schrader inside the lab where the Cambridge biotech startup is developing microneedle skin vaccines as alternatives to traditional flu shots.Jessica Rinaldi/Globe Team

“Conceptually, the idea is simple. You have a patch with a few little things coming out and you stick it on your skin,” said Mark Prausnitz, chemical and biomolecular engineer at Georgia Tech, and chief scientific officer and co-founder of microneedle vaccine startup Micron Biomedical.

But scientists have been working on microneedle patch vaccines for more than two decades. Only a few of them have gone through early clinical trials. None have been approved. And venture capitalists and big pharma have been hesitant to invest in this approach.

Still, challenges with the global distribution of COVID-19 vaccines, which must be stored in refrigerators or freezers, highlight the need for new approaches, said Dr. Mark Poznansky, director of the Vaccine and Immunotherapy Center in Massachusetts. GeneralHospital. “The pandemic has made microneedle vaccines relevant again,” he said.

“Now there has to be a breakthrough study in humans that really shows it works,” he added.

Vaxess was founded by four Harvard Business School classmates who became interested in a method using silk proteins to stabilize vaccines. Schrader hoped the trick, developed by Tufts scientists Fiorenzo Omenetto and David Kaplan, could be used to make vaccines that don’t require cold storage.

“Vaccine developers were intrigued by the technology, but they didn’t know how they were going to make more money with it,” Schrader said.

Kate Skrada, senior research associate in immunology at Vaxess, has been working to develop a test that will look for a range of immune responses from blood samples in the company’s ongoing clinical trials.Jessica Rinaldi/Globe Team

In 2014, Schrader saw a paper by MIT scientists Darrell Irvine and Paula Hammond who combined the stabilizing properties of silk with a microneedle patch to make a vaccine that released slowly into the skin over a few weeks to stimulate responses. stronger immune systems. “It was a perfect extension of our work,” Schrader said.

Vaxess shifted gears to developing its own micro-needle patch, initially working with the team at MIT through a grant from the Bill & Melinda Gates Foundation for a few years. It was not easy.

“It would almost take being naive to try to do what we’re doing,” Schrader said. Maintaining vaccine stability, filling the microneedles evenly and getting them to release the vaccine slowly are each “incredibly complex” issues, he said. Combining them is even more difficult.

The resulting patch is about an inch wide, with an array of 121 transparent micro-needles, each just a fraction of a millimeter long and made from a mixture of silk, sugar and other polymers. A small spring device ensures that people stick the patch on the skin correctly.

“You feel a slight snapping sensation, like a rubber band, but you don’t feel the needles themselves,” Schrader said. “You only wear the patch for five minutes and take it off. But the vaccine stays in your skin and releases slowly for two weeks. »

A view of the Cambridge biotech startup’s skin patch and its 121 micro-needles designed to deliver a flu vaccine just below the surface of the skin.Jessica Rinaldi/Globe Team

Until recently, the company relied heavily on grants from the Gates Foundation and government agencies to fund its work. It has been particularly difficult to raise funds from venture capital firms, which often eschew vaccine startups in favor of biotech companies working on more lucrative drugs for cancer or rare diseases. “We were told many times along the way that we should forget about vaccines and focus on low-volume, high-margin products,” Schrader said.

“COVID changed that dramatically,” Schrader added, because vaccines against the disease were not only important, but very cost effective. “We’ve had inbound calls from venture capital funds that five years ago wouldn’t touch vaccines, and now they’re interested,” he said.

Mario Barro, chief innovation officer at RA Capital, said in an email that the pandemic “inspired” the company “to make vaccine innovation an explicit part of its investment strategy.” Vaxess stood out to the company for its “unique approach” to eliminating the need for cold storage and for the potential ease of delivery, he added.

The Engine, MIT’s Mission BioCapital and Global Health Investment Corporation have also contributed to new Vaxess funds. Ann DeWitt, general partner at The Engine, hopes the startup’s flu study is just the first of many to come. “It lays the foundation for the next set of vaccines and drugs that can fit into this platform,” she said.

Vaxess must first prove that its microneedle patches are at least as safe and effective as existing flu vaccines. A study in mice suggests that the patches better protect mice from the flu. But Posnansky warned that keeping the vaccine in the skin for two weeks could also trigger more adverse reactions to the vaccine, such as swelling, pain or fever. “There’s a kind of ying and yang to it,” he said.

Even if the patches work, Vaxess will face the hurdle of figuring out how to make them in large quantities and at affordable prices. The startup’s manufacturing facility in Woburn can only make 1,000 patches a week by precisely injecting drops of the silk and vaccine mixture into tiny holes in the mould. “The fine-tuning was a major challenge,” Schrader said.

Vaxess hopes to eventually produce 100 million patches per year. Schrader said the Biomedical Advanced Research and Development Authority, part of the US Department of Health and Human Services, has already paid for the design of a facility of this scale. But turning those plans into a building could cost hundreds of millions of dollars, he added. “I am fully aware of the magnitude of the bottleneck this will represent for us.”

Omenetto, one of the Tufts engineers behind the silk technology and an adviser to Vaxess, hopes the startup’s clinical trial will be a long-awaited turning point for the company. “They took a very, very difficult project and turned it into something that’s about to become a reality,” he said. “It makes me feel really good about where the technology is going.”

Ryan Cross can be contacted at [email protected] Follow him on Twitter @RLCscienceboss.