CAMBRIDGE, Mass. — RiboX Therapeutics, a clinical-stage biotechnology company developing circular RNA therapies, announced Thursday that early clinical findings from its experimental treatment for radiation-induced dry mouth have been published in The New England Journal of Medicine.
The peer-reviewed research letter presents results from the first six patients treated with RXRG001 in the ongoing Phase 1/2 SPRINX-1 clinical trial. The investigational therapy is designed to restore salivary gland function in patients experiencing chronic dry mouth and reduced saliva production following radiation treatment for head and neck cancer.
According to the company, patients receiving a single dose of RXRG001 demonstrated sustained improvements in saliva production and reported reductions in dry mouth symptoms over six months of follow-up.
The treatment was generally well tolerated, with no dose-limiting toxicities observed among the six participants across two dosage groups.
RXRG001 also recently received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration for radiation-induced xerostomia and hyposalivation.
“Publication of these first-in-human findings in The New England Journal of Medicine, together with the recent FDA RMAT designation for RXRG001, represents important progress for this program and for the emerging field of circular RNA therapeutics,” said Weiyi Zhang, Ph.D., co-founder and CEO of RiboX Therapeutics.
“We are encouraged by the durable improvements observed in both objective measures of salivary flow and patients’ reported symptoms following a single administration,” Zhang added.
Radiation-induced xerostomia is a common complication among survivors of head and neck cancer. Radiation therapy can damage the salivary glands, resulting in persistent dry mouth that interferes with eating, swallowing, speaking and maintaining oral health.
RXRG001 uses circular RNA technology to deliver genetic instructions for producing aquaporin-1, a protein involved in transporting water across cell membranes.
The experimental treatment is formulated using lipid nanoparticles and administered directly into the salivary gland ducts, with the goal of improving saliva production by restoring water movement within damaged salivary tissue.
All six patients enrolled in the initial treatment groups had experienced chronic dry mouth for at least two years following radiation therapy for head and neck cancer.
Participants received a single infusion of RXRG001 into a parotid gland duct at doses of either 4 or 10 micrograms.
Researchers reported that the treatment procedure was well tolerated. All treatment-related adverse events were mild or moderate and temporary, with no dose-limiting toxicities identified during at least four months of observation.
Patients demonstrated improvements in both objective measures of saliva production and questionnaire-based assessments of dry mouth symptoms.
Improvements in saliva flow were observed as early as seven days after treatment and continued through the six-month assessment.
Among the three patients receiving the initial 4-microgram dose, unstimulated salivary flow increased by 47%, 300% and 450%, respectively, at three months compared with baseline measurements.
Stimulated salivary flow increased by 55%, 1,450% and 131%, respectively, among those patients. Similar improvements were reported in the higher-dose group.
Researchers also observed improvements in patient-reported symptoms within the first month, with benefits generally sustained during subsequent assessments.
“These early findings are encouraging for patients living with radiation-induced xerostomia, a chronic condition that can significantly affect eating, swallowing, speaking, oral health and overall quality of life,” said Dr. Henry Hoffman of the University of Iowa Hospitals and Clinics, lead author of the research letter.
“The improvements we observed in objective measures of salivary flow were accompanied by patients reporting improvements in their symptoms. We look forward to continuing the study to further characterize the safety, durability and potential clinical benefit of this novel approach,” Hoffman added.
Dr. Harry Quon, associate professor of radiation oncology and molecular radiation sciences at Johns Hopkins University School of Medicine, said the findings suggest the possibility of addressing underlying radiation-related damage rather than relying exclusively on symptom management.
“It has been gratifying to see early and sustained improvements in salivary function and quality of life, including patients regaining the ability to comfortably eat foods such as breads and meats,” Quon said.
The company said the findings represent the first reported therapeutic use of circular RNA in humans.
Unlike conventional messenger RNA, circular RNA has a closed-loop molecular structure that may offer advantages in stability and sustained protein production.
However, the findings remain preliminary because the study involved only six patients and did not include a placebo comparison group. Larger studies will be needed to determine whether the improvements can be consistently reproduced and maintained over longer periods.
RiboX said enrollment in the SPRINX-1 trial is continuing, with additional dose levels planned to further evaluate treatment safety, effectiveness and durability.
RXRG001 remains an investigational treatment and has not received FDA approval for commercial use.
