Moderna and BioNTech weren't exactly household names before last year. But their research into messenger RNA quickly came into the spotlight as the coronavirus spread around the world. Now, many countries' best chance at ending the pandemic lies with the effective vaccines these companies developed.
Against this backdrop, the biotechnology incubator that founded Moderna launched on Monday another company focused on the therapeutic potential of RNA, the single-stranded courier of genetic information. The company, Laronde, comes equipped with $50 million in funding from Flagship Pioneering and a lofty goal to upend how diseases are treated, through the use of so-called eRNA, or endless RNA.
In cells, messenger RNA provides the instructions for what proteins need to be made. These instructions don't last very long, though, because to maintain order and guard against outside threats like viruses, cells will chew up stray or unused pieces of genetic material.
Unlike typical messenger RNA, which is linear, eRNA comes as a ring. This shape is critical to Laronde, so much so that the company's name comes from the French word for round. In a ring structure, eRNA doesn't have loose ends for enzymes to latch onto and start the dismantling process, meaning that it could, in theory, remain active for longer and help protein expression last weeks or months.
"Imagine if we could give people a tiny bit of eRNA, and people could then manufacture their own self-healing proteins in their own body. Just think about how that would change how we think about medicines and what medicines are," said Diego Miralles, Laronde's CEO and a partner at Flagship.
To Avak Kahvejian, Laronde's founding CEO and a general partner at Flagship, the company's launch is a major milestone. A biochemist by trade, Kahvejian's PhD concentrated on messenger RNA translation. He joined Flagship about a decade ago, and in late 2017 got Laronde off the ground.
"Pun intended, my PhD came full circle here," he said.
According to Kahvejian, in those earlier days, Flagship was looking into different forms of RNA that were emerging from genomic studies, and noticed some naturally had a closed-loop structure. Yet, most of these circular RNAs didn't code for proteins, which got Flagship thinking about how to coax the cell to read them like it reads messenger RNA, Kahvejian said.
To do this, Kahvejian said his team took inspiration from how viruses trick cells into translating their genetic code. The result is synthetic, circular pieces of RNA that function like perpetual motion machines, according to Kahvejian.
Laronde now believes its eRNA platform can overcome challenges faced by other RNA technologies, as it has the potential to make medicines that are more stable, longer lasting, and that can be administered multiple times and in different ways.
"It opens up a whole new array of therapeutic possibilities that haven't existed before," Miralles said.
Laronde admits it has exceptionally ambitious goals. The company said in a Monday press release that it plans to hire more than 200 people in the next two years, while building a modular and scalable factory for clinical and commercial manufacturing. It's also setting an incredible target of producing as many as 100 eRNA medicines over the next decade. Few drug companies, apart from the largest pharmaceutical and biotech firms, are so prolific.
“Let me just say this: if two years ago, I had read that press release. I would have said, 'Those people are crazy.' But the world has changed," Miralles said. "It would be crazy not to be aspirational."
Miralles pointed to the rapid development of messenger RNA vaccines as one example of how fast the field of translatable RNA is growing. But, while Moderna and BioNTech have set the standard with their shots, success was far from guaranteed, nor apparent from the outset.
Moderna, for example, has been working on messenger RNA therapeutics for more than a decade. And though it currently has a market value of $65 billion alongside a broad pipeline of experimental programs, those are relatively new developments. The lipid shell that protects the mRNA of its medicines alone took years to perfect. The company had also received criticism from investors before the pandemic about its decision to turn its focus to vaccines rather than drugs.
Miralles notes that Laronde doesn't expect to solely develop and bring to market 100 medicines, but rather uncover many potential therapies and then evaluate the best path for each. There will be programs the company takes from start to finish, he said, but also ones which get sold or used to create spinouts.
Such deals could provide an important source of cash as Laronde gets further off the ground. Miralles didn't say how long he expects the $50 million from Flagship to last, but maintained that he wasn't worried about raising more money. "We're building a company that is going to have a huge impact, and I know there are going to be a lot of people that are excited to be a part of it."
As for what diseases the company will target, many broad categories are on the table. Miralles said eRNA's ability to be redosed could make it a valuable treatment option for chronic diseases. He said hematology, oncology, neurology, immunology and inflammation are just some of the research areas that could be addressed with Laronde's technology.
But as a guiding principle, Laronde will be following proteins of interest. That eRNA is "programmable," meaning the genetic code can be swapped in and out, should allow the company to more easily expand into different disease areas, according to Miralles and Kahvejian.
"Think about a CD player. It's all the same," Miralles said. "We have a master construct, eRNA, and we just swap the protein coding cassette, and we can make another product and another product."