In 2017, scientists at Flagship Pioneering were exploring different kinds of ribonucleic acid, or RNA, focusing on an unusual form of the molecule that had a circular shape, rather than a linear strand with two ends.
“When I saw that, I got excited,” said Avak Kahvejian, a general partner at the Cambridge venture capital firm. “I thought it was a way the cell was making really robust, stable RNAs, which are usually very unstable.”
For the last four years, a small team at Flagship has been working to turn this emerging science into drug-making capabilities, and now they are coming out of stealth mode with a startup called Laronde. The biotech, which Flagship has funded with $50 million, is based on a proprietary molecule its scientists call “endless RNA,” an approach the company hopes will allow the body to produce its own proteins for weeks or months to treat diseases.
It’s what Diego Miralles, who joined Flagship in January as a partner and is chief executive of Laronde, calls the Holy Grail.
“Imagine if we could give you a tiny bit of endless RNA, and you make your own proteins,” Miralles said. “A patient becomes a factory of a therapeutic protein.”
It wouldn’t be Flagship’s first run at turning the human body into a type of drug-making factory — that was the original idea behind its breakout biotech Moderna, which uses a synthetic version of messenger RNA to stimulate the body to produce antibodies against COVID-19.
Laronde’s problem: Unlike other forms of RNA, including messenger RNA, the closed-loop structures known as long noncoding RNAs do not produce proteins. Traditional RNA strands use one of their ends to latch onto ribosomes, but as Kahvejian put it, “circles don’t have ends.” The round form of RNA, though more stable, had to be tweaked so that it could work with the protein-making machinery of cells.
Miralles said endless RNA, which the company shortens to “eRNA,” has the potential to overcome challenges associated with most protein-based medicines.
Unlike small-molecule drugs, which can be taken orally and enter cells to treat diseases, protein therapies are large and typically are more difficult to make and deliver. Protein-based drugs traditionally come with cumbersome manufacturing and administration processes — all factors that drive up their cost and limit access, he said.
Kahvejian, who was the founding CEO of Laronde and co-inventor of its technology, said that with eRNA, the “code” for a protein can be changed at will, so patients could potentially receive different drugs or different doses of the same therapy using the same basic construct.
“We are bringing in software that is persistent enough to have therapeutic impact, but transient enough that it is not a permanent change and allows us to address a wide range of diseases,” Kahvejian said.
The Laronde team is in no rush to disclose which diseases it will target first, but Kahvejian said the company has the potential to generate 100 drugs in 10 years. (Moderna had similar ambitions, and 10 years later its COVID-19 vaccine is on the market, while it is running about a dozen clinical trials in other areas.)
The categories Laronde could go after are broad, ranging from genetic diseases and cancer to dermatology and infectious diseases. The company said it has seen promising results in animal trials, and the plan is to run several clinical programs at the same time.
Of course, it has a long way to go. Laronde has 50 employees, and it plans to add another 200 over the next two years.
The biotech will have plenty of room to grow, with two floors at 101 South St. on the Boynton Yards campus in Somerville, a new lab and office space expected to open later this year. The 290,000-square-foot, nine-story building will be fully leased by four Flagship companies, including Tessera Therapeutics, a “gene writing” startup that was launched last year and has raised $280 million, and the single-cell sequencing startup Cellarity.