Ring Therapeutics

Ring is tapping 'useful viruses' to help boost gene therapy delivery. (Ring Therapeutics)

Ring Therapeutics

Taking a new approach to gene therapies with anelloviruses, a family of viruses found in all humans that have the potential to break through the problems typically associated with adeno-associated virus-based vectors.

CEO: Tuyen Ong, M.D.

Founded: 2017

Based: Cambridge, Massachusetts

Clinical focus: While clinical testing is still on the horizon, Ring is exploring a variety of potential areas to go after, including vaccines, ophthalmology and cardiology, given what it calls “an embarrassment of riches” that comes with the potential of anelloviruses.

The scoop: Anelloviruses live in harmony with the human immune system, and they have the potential to transform the aging field of AAV gene therapies. Ring thinks it can break through the limitations of AAV gene therapies, which have included tissue-specific tropism, tolerability concerns, lack of potency, and the problem of being unable to re-dose.  The timing is optimal: An FDA advisory committee discussed AAV gene therapies, including toxicity risks tied to the field, in early September.

What makes Ring fierce: Viruses have been top of mind for billions of people the past 18 months because of the devastation wrought by the COVID-19 pandemic.

But one family of viruses could hold the key to a new set of gene therapies that try to do away with tolerability issues, tissue-specific tropism, lack of potency and re-dosing limitations.

Those viruses, known as the anelloviruses, are found in all humans and have a genetic diversity that establishes “distinct advantages as vectors for delivery of DNA/RNA payloads,” said Tuyen Ong, M.D., CEO of Ring. The biotech published its findings in a July Cell Host & Microbe report.

Anelloviruses were found years ago as a result of incubator Flagship Pioneering pondering whether a set of “useful viruses” could address the shortcomings of adeno-associated virus-based vectors, or AAV gene therapies. Toxicity issues and other problems tied to AAV gene therapies were up for discussion in early September at the FDA through the Cellular, Tissue and Gene Therapies advisory committee. The committee also made recommendations.

Ring is no stranger to AAV gene therapies. Roger Hajjar, M.D., head of research and development at Ring, has worked in the field for more than two decades and ran the first trial of gene therapy in heart failure patients. The clinically trained cardiologist also ran the cardiovascular center at Mount Sinai for about a decade before joining Ring. 

The potential for anelloviruses’ potency would “decrease the requirements for the astronomically high dosing that the FDA is worried about,” Hajjar said, referring to the September meeting.

What we’ve seen is that these anelloviruses have naturally evolved through millions of years, existed in mammals, and have somewhat lived in harmony with our immune system, and so that gives them a really distinct advantage when you’re looking at administering them,” Ong said.

From an immune perspective, Ring hasn’t been able to detect neutralizing antibodies developed against these viruses, Ong added.

Ring has been able to show the ability to administer more than one dose in an animal model, but the biotech hasn’t disclosed its data yet. That could be critical in addressing childhood diseases and other indications where gene therapies can't be administered in repeated doses.

“If you don’t have that durable effect, and you’re not able to re-treat because of neutralization, you’re kind of stuck right now, and the anellos really have the ability to address that feature,” Ong said.

COVID-19 presents a “pretty neat opportunity to look at re-doseability,” Ong said. Vaccines for the pandemic or other viruses could be one of many paths Ring takes. The spread of variants and the increasing call for booster doses, all the way up to the White House, has spotlighted a “continued need overall in addressing” the COVID-19 pandemic.

“I think we’re talking about vaccines in general. There are a number of opportunities. We haven’t disclosed which specific viruses we’re going to talk about right now. I suspect they're not just going to be limited toCOVID,” Ong said.

Given Ong and Hajjar’s backgrounds, other potential routes include ophthalmology and cardiology. Ong says the biotech has an “embarrassment of riches” when it comes to the possibilities of anelloviruses. Ong previously headed Biogen’s ophthalmology disease franchise after his company, Nightstar Therapeutics, was acquired for $877 million in 2019. Ong’s resume also includes work in rare and genetic diseases.

Ring’s leadership resume could be critical if the biotech decides to go after viruses. Simon Delagrave, Ph.D., senior vice president for platform and biology, worked at Sanofi for more than a decade, including nearly four years as senior director for virology. Viral Genomics Director Nathan Yozwiak, Ph.D., worked with the World Health Organization as a consultant during the Ebola outbreak and was associate director of the Broad Institute’s viral genomics unit. 

The upstart is also led by John Huynh, Ph.D., senior vice president of technical operations, who is focused on building out the anello vectors to do preclinical testing, setting up a path for human trials. Huynh was previously vice president of PTC Therapeutics’ gene therapy unit.

Investors: T. Rowe Price Associates, Altitude Life Science Ventures, Partners Investment, UPMC Enterprises and others.

Ring Therapeutics