When Jacob Becraft addressed a bustling party of a hundred-plus employees, friends, and investors at his startup’s lab last month, he credited messenger RNA for bringing everyone back together in one room.
His remarks carried a double meaning. Yes, the mRNA vaccines had allowed the large group to gather in person — not a mask in sight. But Becraft’s Strand Therapeutics is also one of several Boston-area startups buoyed by the success of the COVID-19 shots and hoping to expand the reach of mRNA medicines into cancer and other diseases.
That night, Strand was celebrating the opening of its new headquarters in Fenway — a neighborhood known for baseball, not biotech. As the packed house chattered over cocktails and a musician playing acoustic covers, Becraft, the startup’s cofounder and chief executive, was quietly reveling in another milestone.
Investors in the nearly five-year-old startup have topped off a previously announced financing with an additional $45 million, bringing the total to $97 million, Strand told the Globe. The funds will help Strand start a clinical trial of its first experimental medicine, a cancer immunotherapy, likely in the second half of 2023.
The new money comes as anticipation builds for companies to prove that the COVID-19 vaccines were not one-hit wonders for mRNA technology. More than a dozen Massachusetts companies are developing mRNA-based medicines, which use the short-lived genetic molecule to produce a therapeutic protein.
The potential applications are vast. Cambridge-based Moderna already has more than 40 mRNA programs underway for cancer, genetic conditions, and infectious diseases. Yet several smaller and newer companies, Strand included, believe that a second generation of mRNA technologies is needed to broaden the genetic molecule’s reach.
“Messenger RNA has the potential to revolutionize medicine,” Becraft said. “But it will be insufficient to have that revolution happen without new technological advancements.”
One problem with the first generation of mRNA medicines is that scientists don’t have great ways to control which parts of the body they get into. Strand has devised a technology that lets mRNA therapies sense when they are inside a cancer cell and, only then, rapidly begin producing a potent cancer drug. By keeping the therapy inactive in healthy cells, toxic drugs can be restricted to tumors.
“What they’re doing is really different than just about any mRNA company we’ve been looking at,” said Pegah Ebrahimi, cofounder and managing partner of FPV Ventures, a San Francisco-based venture capital fund that led Strand’s new financing.
Becraft began working on “mRNA 2.0″ before the first generation of the technology had proved its worth. In 2013, he went to MIT for grad school, where he joined the lab of synthetic biologist Ron Weiss, who had pioneered the development of genetic circuits — DNA molecules that know when to turn genes on or off by sensing their surroundings.
Weiss had recently won funding from the Defense Advanced Research Projects Agency, a research arm of the Pentagon, to develop genetic circuits based on mRNA instead of DNA. It was a far-fetched project at a time when many scientists were skeptical that mRNA could ever be used as a medicine.
“The vast majority of people did not believe in it,” said Tasuka Kitada, who was a postdoctoral researcher in Weiss’s lab.
A group helmed by Becraft, Kitada, Weiss, and MIT professor Darrell Irvine spent about six years thinking through all the possible ways to develop genetic switches with mRNA.
They landed on a system based on small genetic molecules called microRNAs, which naturally control how mRNA is used to make proteins. Because different microRNAs are found in different parts of the body, scientists can program mRNA to shut down when it detects particular microRNAs.
But the real trick that the MIT scientists devised was a way to activate mRNA in the presence of particular microRNAs — a much more useful application for therapies. The technique involves a protein that binds to and represses the mRNA therapy until a specific microRNA removes the protein.
Becraft and Kitada cofounded Strand in December 2017, with Irvine and Weiss as scientific cofounders and advisors. Before the pandemic, the startup’s story was a tough pitch to investors. They didn’t raise money to hire their first scientist until 2019.
“The first generation of mRNA therapies was a moonshot,” said Kitada, who is Strand’s president and head of research and development. “And we were saying that one day it’s possible we’re going to land on the moon, and when we do, we’re going to need all this sophisticated technology.”
The company’s first mRNA therapy encodes an immune protein called interleukin-12. Scientists have known since the 1990s that IL-12 can trigger immune cells to attack tumors, but the protein is toxic when infused body-wide. Strand hopes its technology will keep the potent protein restricted to cancer cells. Its mRNA therapy is also designed to replicate itself once inside a tumor, which Strand believes will spur a better immune response.
Many firms have attempted to make safer IL-12 therapies over the years, including Moderna, whose pharma partner, AstraZeneca, recently dropped the program. Moderna said earlier this month it is “evaluating next steps” for the drug.
Becraft is considering an initial focus on breast cancer, melanoma, and head and neck cancers, but he thinks the therapy would have broad applications to many other cancers as well.
As Strand grew during the pandemic, fueled by a partnership with Chinese drug developer BeiGene and an initial $52 million financing in 2021, the startup had a hard time finding a single lab to house its growing number of employees. So the company was split up across six labs in Cambridge, Watertown, and Boston’s Seaport neighborhood.
A few months ago, Strand began moving most of its employees into a new 65,000-square-foot lab and office space in Fenway. Becraft said the nearly 80-person company is now funded into 2024.
Strand will face plenty of competition. British startup VaxEquity and two San Diego-based companies, Arcturus Therapeutics and Replicate Biosciences, are also developing self-replicating mRNA medicines that multiply on their own inside the body. Other groups, including Cambridge startup Kernal Biologics, are developing mRNA therapies that are selectively activated in cancer cells. A 2018 paper from Moderna shows the big firm is privy to that idea, too.
Weiss thinks there’s “tremendous room” for new companies to emerge with ideas for making more sophisticated mRNA therapies.
“Obviously, the vaccines have really altered the way we think about using RNA for human therapy,” he said. “We’re really just at the beginning.”