RiboX Therapeutics Ltd. (RiboX), a pioneering biopharmaceutical company, focused on discovering and developing fully engineered circular RNA therapeutics, announced that the US Food and Drug Administration (FDA) has cleared its IND application for the Phase I/IIa Study of RXRG001 (SPRINX-1 Study) on October 25^th, 2024. RXRG001 is the first-ever circular RNA therapy to receive FDA IND clearance. This important advancement marks a significant milestone as circular RNA drugs advance into the clinical development phase. The first-in-human SPRINX-1 study is designed to evaluate the safety and efficacy of RXRG001 in patients with radiation-induced-xerostomia (RIX) (dry mouth) and hyposalivation (low saliva secretion).

Xerostomia and hyposalivation are common side effects of radiation therapy in head and neck cancer (HNC) patients. The incidence of HNC is increasing and has become the sixth most common malignant tumor worldwide.  Radiation therapy, a main treatment for HNC, often results in damage to salivary glands and a significant decrease in saliva secretion, frequently leading to dry mouth, difficulties in chewing and swallowing, impaired oral health, and diminished quality of life. It has been two decades since the last xerostomia treatment was approved by the FDA. Patients reported that current treatments are ineffective, temporary, and costly. There is a significant unmet medical need to develop a new treatment for xerostomia and hyposalivation.

RXRG001 is a proprietary product developed using innovative circular RNA technology. In recent years, circular RNA has emerged as the next generation mRNA therapy due to its high protein expression efficiency, low immunogenicity, and manufacture stability. RXRG001 consists of the circular RNA coding human aquaporin 1 (hAQP1, a water channel protein of cell membrane), encapsulated in lipid nanoparticles (LNPs). RXRG001 increases saliva production by restoring water permeability via overexpression of hAQP1, therefore it alleviates dry mouth symptoms.  Non-clinical studies demonstrated a favorable risk and benefit profile of RXRG001 in animal models. For instance, a single administration of RXRG001 led to a significant increased salivary flow which was sustained for about four weeks.

"RIX is a devastating life-long health issue for patients with HNC. Although radiation therapy improves patients' survival, its damage to the salivary glands leads to an impaired quality of life of many cancer survivors," said Dr. Yizhen Xu, Chief Medical Officer of RiboX. "RXRG001 may offer a potential effective and sustained therapeutic option for RIX patients. We are excited to conduct clinical trials to further evaluate its efficacy and safety in patients."

"The FDA's clearance of the IND application for RXRG001 is an acknowledgment of our innovative capabilities, robust technology, and competitiveness in the field of circular RNA therapeutics." Dr. Weiyi Zhang, Chief Executive Officer of RiboX, stated "RiboX will advance the clinical development of RXRG001, continue leveraging the unique advantages of circular RNA technology in therapeutic applications, and introduce more pioneering treatments to patients around the world."