RiboX Therapeutics Ltd. announced on March 9, 2025, that the first patient has been dosed in its first-in-human Phase I/IIa clinical trial evaluating RXRG001 for radiation-induced xerostomia (RIX) and hyposalivation. The SPRINX-1 trial represents a significant milestone as the first clinical study of a circular RNA therapeutic.
Xerostomia, commonly known as dry mouth, and hyposalivation are frequent side effects experienced by head and neck cancer patients following radiation therapy. These conditions develop when radiation damages salivary glands, substantially reducing saliva secretion and leading to difficulties in chewing, swallowing, and maintaining oral health, ultimately diminishing patients' quality of life.
Novel Circular RNA Technology
RXRG001 utilizes proprietary circular RNA technology to deliver the genetic code for human aquaporin 1 (hAQP1), a water channel protein found in cell membranes. The circular RNA is encapsulated in lipid nanoparticles (LNPs) for delivery to target tissues.
The therapy aims to increase saliva production by restoring water permeability through hAQP1 overexpression in damaged salivary glands. Preclinical studies have shown promising results, with a single administration of RXRG001 significantly increasing salivary flow for approximately four weeks in animal models.
RXRG001 received FDA Investigational New Drug (IND) clearance on October 25, 2024, making it the first circular RNA therapy to advance to clinical trials.
Clinical Trial Progress
The first patient was dosed at the University of Iowa under the supervision of Principal Investigator Henry T. Hoffman, MD, MS, FACS, Professor of Otolaryngology and Editor of Iowa Head and Neck Protocols.
"Patients suffering radiation-induced xerostomia face a need for new therapeutic options. RXRG001 introduces an innovative approach offering hope for my patients," commented Dr. Hoffman. "We are proud to be the first site to treat a patient with RXRG001 and look forward to continuing to collaborate with RiboX and other investigative centers to rapidly enroll patients in this FIH trial. I am glad that our first patient is tolerating the investigational product well."
Addressing an Unmet Medical Need
The development of RXRG001 addresses a significant gap in treatment options for patients suffering from radiation-induced xerostomia. Current management approaches for this condition are largely symptomatic and often provide inadequate relief.
"We are privileged to work with Dr. Hoffman at University of Iowa and our other esteemed Principal Investigators whose patients battle for their quality of life under the profound impact of radiation-induced xerostomia, in aftermath of their cancer treatment and survivorship," shared Haifa Tyler, Head of Clinical Operations at RiboX. "It is an honor to initiate the first-ever circular RNA therapy clinical trial and now a pivotal moment in the dosing of our first patient."
Advantages of Circular RNA Technology
Circular RNA represents a promising advancement in RNA therapeutics. Unlike linear messenger RNA (mRNA), circular RNA features a covalently closed single-stranded structure that provides several advantages:
- Enhanced stability against degradation
- Lower immunogenicity
- Tunable protein expression
- Improved manufacturing stability
These properties potentially overcome limitations associated with current mRNA therapeutics and may enable more effective RNA-based treatments.
Yizhen Xu, MD, PhD, Chief Medical Officer of RiboX, emphasized the significance of this milestone: "Today's accomplishment marks an important milestone for both RiboX and most notably for xerostomia patients. We are grateful to our patients and investigators for their contribution to our clinical trials. RiboX is committed to introducing more novel treatments to patients around the world by leveraging our innovative circular RNA technology."
About RiboX Therapeutics
Founded in 2021 by Drs. Ling-Ling Chen, Dan Peer, and Weiyi Zhang, RiboX Therapeutics is a global biotech company dedicated to developing fully engineered circular RNA therapeutics. The company maintains operations in Princeton, NJ, USA; Rehovot, Israel; and Shanghai, China.
Beyond radiation-induced xerostomia, RiboX's pipeline includes potential treatments for monogenic rare diseases, autoimmune conditions, and metabolic disorders. The company's focus on circular RNA technology positions it at the forefront of next-generation RNA therapeutics development.
The SPRINX-1 trial is currently enrolling patients, with additional information available through the clinical trial registry (NCT06714253) and the company's website.
