Looped RNA drug raised saliva flow in small trial for radiation dry mouth

A new type of RNA medicine increased saliva production in people with long-lasting dry mouth caused by radiation treatment for head and neck cancer. The results come from a small first-in-human study by RiboX Therapeutics, published in The New England Journal of Medicine.¹ It is the first published clinical trial of a circular RNA drug used as a treatment, according to Inside Precision Medicine.¹

Only six people were treated, every one of them knew what they were getting, and follow-up so far runs about four months. The study shows that the drug can be given and that saliva output rose. It does not yet show how well or how long it works in a larger group.

What happened

Radiation therapy for head and neck cancer often damages the salivary glands and sharply cuts saliva production. That can lead to dry mouth, trouble chewing and swallowing, poorer oral health and a lower quality of life.² The condition is known as radiation-induced xerostomia.

RiboX’s drug, called RXRG001, delivers RNA that tells gland cells to make aquaporin-1, a protein that acts as a water channel and lets water flow out of cells and into the mouth.³ The RNA is packed inside lipid nanoparticles, tiny fat bubbles that help it get into cells.¹ The idea is to restore the flow of water through the gland cells that survive radiation.²

What makes the drug unusual is the shape of its RNA. Ordinary messenger RNA (the kind used in some COVID vaccines) is a strand with two loose ends. Circular RNA is closed into a loop, which protects it from being broken down and, in theory, lets cells keep making the protein for longer.¹

The evidence so far

The study enrolled six people who had dry mouth for at least two years after radiation for head and neck cancer.¹ Three received 4 micrograms of the drug and three received 10 micrograms. Each got a single infusion into one parotid gland, the large salivary gland in front of the ear that makes thin, watery saliva.¹ The procedure takes less than 10 minutes.¹

According to Inside Precision Medicine, the drug increased saliva production in patients with chronic dry mouth.¹ A summary published by Wisevoter, based on reporting by Firstwordpharma, gave numbers for the lower-dose group: in its three patients, unstimulated saliva flow (saliva made without chewing or other prompting) rose by 47%, 300% and 450% after three months compared with the start.⁴ The sources given to Biohack do not include the figures for the higher-dose group.

On safety, the treatment was generally well tolerated in this small group. No dose-limiting side effects linked to the infusion were seen during at least 120 days of follow-up, and treatment-related side effects were short-lived and graded 1 or 2, the mildest grades.¹

Inside Precision Medicine also described one patient who had lived with dry mouth for 17 years. A few weeks after treatment, his ability to make saliva came back, and later he found he could swallow a cookie without drinking water for the first time in years.¹ That is one person’s experience, reported through the company, not a measured result for the group.

“When we look at the paper and those numbers, it’s kind of cold because we don’t know how those numbers change patients’ lives,” RiboX CEO Weiyi Zhang told Inside Precision Medicine.¹

What it does not show yet

This first part of the trial is open-label and single-arm: everyone got the drug, and there was no comparison group on a placebo (a dummy treatment).⁵ Without a placebo group, it is hard to separate the drug’s effect from natural ups and downs in saliva or from people’s expectations.

Six people is also far too few to judge how often the drug helps or to spot rare side effects. Inside Precision Medicine noted that questions remain about how long the effect lasts, how consistent it is from person to person, and how safe it is.¹ In earlier animal studies, a single dose raised saliva flow for about four weeks.² Whether the effect lasts longer in people, and whether repeat doses would be needed, is not shown in the sources.

Who is behind it

RiboX Therapeutics is a Shanghai-based company that develops circular RNA therapies.⁶ It sponsors the trial, called SPRINX-1.⁵ Stanford Medicine is one of the sites recruiting patients.⁷ The detailed accounts of the results available here come through the company’s CEO and through news coverage, not from an independent review of the data.

The US Food and Drug Administration (FDA) allowed the trial to begin in October 2024. At the time, RiboX said this made RXRG001 the first circular RNA therapy to receive that clearance.⁶ Wisevoter reported that in September 2026 the FDA gave the drug a Regenerative Medicine Advanced Therapy designation, a program meant to speed up review of promising treatments for serious unmet needs.⁴ That designation is not an approval. The company’s study page says the drug is still investigational and cannot be sold as a treatment for dry mouth.³

How it fits the field

Using aquaporin-1 to treat radiation dry mouth is not a new idea. Earlier clinical studies used modified viruses to carry the aquaporin-1 gene into salivary glands and found it may restore some gland function.¹ RiboX’s approach uses RNA in fat bubbles instead, which does not insert anything into the patient’s own DNA.¹

The company deliberately chose a disease where it could measure a clear, direct effect for its first program. “For our first program, we wanted to read out exact pharmacodynamic markers,” Zhang said, meaning signs that the drug was doing something in the body.¹ Injecting straight into one gland also keeps the procedure simple and makes the drug’s activity easier to check.¹

RiboX has said there is currently no effective treatment for radiation-induced dry mouth in clinics.⁶ For the wider field, the result matters as an early sign that circular RNA can produce a measurable effect in people.¹

What to watch next

The trial is continuing. Researchers are testing higher doses and looking at whether more drug gives a bigger effect, how long the effect lasts, and longer-term safety.¹ According to the trial registry, the full study plans to enroll about 42 people.⁵ The first part tests rising single and repeated doses in one gland; a second part will give the drug to both parotid glands and compare it with a placebo, with neither patients nor doctors knowing who got which.⁵

The trial’s main goals are counts of side effects over up to 60 weeks.⁵ The registry lists August 2027 as the expected primary completion date, while Wisevoter reported the study is expected to finish by mid-2027.⁵⁴ The placebo-controlled results will be the first real test of whether the saliva gains seen in these six people hold up.