A Shanghai-based startup quietly became the first in the world to start a clinical trial for a circular RNA therapy, a cutting-edge form of genetic medicine that could provide new ways to treat chronic diseases.
Circular RNA is intended to strike a balance between short-lived mRNA therapies and permanent gene therapies. If it works, it could provide patients with a potentially cheaper and safer alternative, and there’s a race to get there first. Investors have poured $1.7 billion into three US companies looking to develop circular RNA treatments.
But RiboX Therapeutics got to human trials first. Yet its announcement on March 9 went largely
unnoticed
, or unacknowledged, in the US. Since 2021, RiboX has kept a low profile.
“They are intentionally very stealthy,” Mitchell Mutz, an entrepreneur partner at Vivo Capital, one of RiboX’s investors, told
Endpoints News
. “There’s a reason it’s flown under the radar: It’s not based in Cambridge, Massachusetts.”
The pharmaceutical industry is
increasingly looking to China
as a source of new drugs that can compete on a global scale. And RiboX is among a growing number of companies that
appear to be outpacing their US counterparts
in pushing the needle on genetic technologies.
“I don’t really see American biotech as competitive anymore,” said R. Alexander Wesselhoeft, a co-founder of the circular RNA startup Orna Therapeutics and currently director of RNA Therapeutics Core at Mass General Brigham.
RiboX CEO Weiyi Zhang declined multiple interview requests. According to PitchBook and LinkedIn profiles of people associated with the company, RiboX has raised $110 million, but Mutz and Zhang would not comment on that figure.
“Since day one of RiboX, I have decided to focus on science and program development, and stay below the radar as much and as long as we can,” Zhang wrote in an email.
The Boehringer Ingelheim Venture Fund confirmed to Endpoints that it is also an investor in RiboX but didn’t respond to additional questions. Qiming Venture Partners includes the startup in its portfolio on its website. Eisai Innovation, Lilly Asia Ventures and Temasek are also investors in the startup, according to Mutz, who has been on the startup’s board since last summer.
Eisai, Lilly and Qiming did not respond to requests for comment, and a spokesperson for Temasek would not confirm or deny if it was an investor.
Moderna and other mRNA developers have said the messenger molecule can be used to deliver instructions for practically any therapeutic protein into the body. But the linear strings of mRNA used in Covid-19 vaccines are short-lived. Those quick bursts of protein expression work well enough for a vaccine, but have constrained their use as therapies for chronic diseases.
Circular RNA provides an alternative. Several lab studies have shown that when the loose ends of mRNA are strung together, the resulting circular molecule is more stable. Several Cambridge-based companies — Orbital Therapeutics, Orna Therapeutics and Sail Biomedicines — have raised large amounts of capital to develop circular RNA therapies that allow cells to pump out therapeutic proteins for weeks instead of days.
Sail Biomedicines
, once viewed as “
Moderna 2.0
,” is perhaps the biggest bet on circular RNA therapies with $750 million in funding. MIT spinout
Orna Therapeutics
is the US biotech that’s farthest along, with plans for clinical trials in 2026 using circular RNA for in vivo immune cell therapies. Sail and Orbital have not announced clinical trial plans yet.
RiboX said that it treated the first patient with its circular RNA therapy in early March. The RNA encodes a water channel called human aquaporin 1. RiboX hopes the protein will increase saliva production and treat dry mouth in people whose salivary glands have been damaged from radiation used to treat head and neck cancer.
A single dose of the therapy boosted saliva flow for roughly four weeks in animal models, according to the company’s press release.
While many Chinese biotech companies often focus their initial clinical efforts in China, RiboX got FDA clearance to test its therapy in the US. The company has an office in Princeton, NJ to oversee the
clinical trial
, which is underway at the University of Iowa. Henry T. Hoffman, a professor of otolaryngology and radiation oncology at the university who is leading the study, declined an interview request and referred questions to RiboX.
Mutz said that injecting circular RNA in or near the salivary glands helped overcome one of the biggest challenges for any RNA medicine: delivering it to the right part of the body.
“They didn’t necessarily want to go to an organ that was hard to target,” Mutz said. “So there is something to be said for not trying to solve everything at once.”
RiboX is based on the work of RNA biologist Ling-Ling Chen at the Shanghai Institute of Biochemistry and Cell Biology in China and lipid nanoparticle researcher Dan Peer at Tel Aviv University. Neither responded to interview requests. Zhang, the company’s CEO and co-founder, previously led Boehringer Ingelheim’s External Innovation Hub China in Beijing.
“Because their academic founders have been doing this for a long time, they weren’t so far from having something clinical when they started,” Mutz said. And, he added, that the RiboX investment came at a “reasonable price” and not with a “super high valuation” like its US competitors.
There are very few public details on RiboX’s technology, but based on the company’s website and publications from RiboX founders, Wesselhoeft said that it looks like “the technology that everyone else is using, which is essentially MIT and Orna’s technology.”
Zhang said in an email that the comparison to Orna’s technology was “false” and that the company’s “research and innovation are original, proprietary, and well protected,” she wrote.
Mutz said that RiboX’s intellectual property with “predated” or “was differentiated enough” from Orna and other US companies for Vivo Capital to be comfortable with the investment. He also emphasized that RiboX’s ability to physically make circular RNA, a potential bottleneck in moving from the lab bench to the clinic, was where the startup “really shined.”
“They had a circularization technology that gave them a good yield so that this would be scalable and manufacturable,” Mutz said. “Professors don’t often think about that stuff. And this is exactly where academic spinouts go to die. But the company always articulated this from day one.”
