RNA research has come a long way, leading to commercialized vaccines and a growing list of therapies in development. But this work just scratches the surface of how RNA can transform medicine, according to Giuseppe Ciaramella, co-founder and CEO of Orbital Therapeutics.

Orbital launched last September with a plan to deploy a suite of technologies toward the development of therapies that advance RNA well beyond its current capabilites. Now the Cambridge, Massachusetts-based startup has $270 million to help it execute on that vision. The Series A financing announced Wednesday was led by ARCH Venture Partners.

Orbital spun out of Beam Therapeutics with licenses to that biotech’s technology for designing and manufacturing mRNA for applications in human disease. Ciaramella, who is still serving as president at Beam, said the original idea came from a conversation with John Evans and Kristina Burrow at ARCH. Beam’s research focuses on developing therapies based on its base-editing technology. Ciaramella said the discussion centered around trying to find value for that platform beyond gene editing. They concluded the best way to do that would be by forming a new company.

In addition to the licenses to Beam’s technology, Orbital has struck additional deals to bring in more technologies. The startup acquired Circ Bio a Stanford University spinout researching therapies based on circular RNA, which offers the potential for a longer-lasting therapy. (South San Francisco-based Circ Bio is not to be confused with Chicago-based CiRC Biosciences.) Orbital isn’t the only biotech startup pursuing circular RNA therapies. Cambridge-based Orna Therapeutics is developing circular RNA therapies for cancer and genetic diseases. Last year, Orna signed on Merck as a research partner in diseases that were not disclosed. Two years ago, venture capital firm Flagship Pioneering unveiled circular RNA startup Laronde.

Ciaramella said Orbital’s ability to work with both linear RNA and circular RNA gives Orbital the opportunity to take the most appropriate approach to the diseases the startup wants to pursue.

“We don’t need to add more [technologies] but we are certainly not going to stop looking for innovation that might bring some advantages,” Ciaramella said. “The toolbox right now is one of the deepest that any company has been able to assemble.”

Orbital will apply that toolbox to three areas: next-generation vaccines, protein replacement therapies, and immunomodulation. In protein replacement, the goal is to develop therapies that don’t require frequent dosing. Whereas linear RNA produces a needed protein and then goes away after it finishes its work, circular RNA offers the potential of continuous production of a therapeutic protein. Orbital’s immunomodulation research includes in vivo CAR T cell therapies for cancer. The applications Orbital is pursuing exclude RNA interference, which is the focus of Alnylam Pharmaceuticals, the former company of Orbital co-founder and Chairman John Maraganore.

Orbital currently has about 39 employees, most of them based at the startup’s Cambridge headquarters. The company also keeps an outpost in South San Francisco, where Circ Bio was, giving the company proximity to Orbital scientific co-founder Howard Chang, who is a professor of cancer research and genetics at Stanford.

The Series A cash is newly raised money. Ciaramella said the company’s launch last September sparked several investor inquiries that progressed to deeper discussions in late 2022 and early this year. As for the size of the financing, Ciaramella said platforms need critical mass for the research to be done in a meaningful way. Orbital will work on several programs in parallel, which should help all of the programs collectively, Ciaramella said. Deploying the technology to a relatively broad opportunity de-risks the approach, he explained. It also enables the learnings from one program to be applied to the other ones.

Not all of the programs will move at the same pace, and the science will dictate which ones advance more quickly, Ciaramella said. Some of the protein replacement research as well as next-generation vaccines could move more quickly because the research in these areas is more advanced than its work in in vivo CAR T therapy. But Ciaramella added that this cell therapy research has also made progress, having already achieved proof of concept in animal testing.

Ciaramella said the Series A round should support Orbital for “several years” before the startup will need to raise more money. The new capital will enable Orbital to optimize the platform and advance at least one of the programs to an investigational new drug application.

Participants in Orbital’s Series A financing include earlier investors a16z Bio + Health and Newpath Partners. The round also brought in new investors Abu Dhabi Growth Fund, Redmile Group, Exor N.V., Invus, Moore Strategic Ventures, iGlobe Platinum Fund Group, Casdin Capital, Agent Capital, Alexandria Venture Investments, Rellim Capital Management, Heritage Medical System as well as other undisclosed investors.

Public domain image by Flickr user NOAA Satellites