AQP1

A Shanghai-based startup quietly became the first in the world to start a clinical trial for a circular RNA therapy, a cutting-edge form of genetic medicine that could provide new ways to treat chronic diseases. Circular RNA is intended to strike a balance between short-lived mRNA therapies and permanent gene therapies. If it works, it could provide patients with a potentially cheaper and safer alternative, and there’s a race to get there first. Investors have poured $1.7 billion into three US companies looking to develop circular RNA treatments. But RiboX Therapeutics got to human trials first. Yet its announcement on March 9 went largely unnoticed , or unacknowledged, in the US. Since 2021, RiboX has kept a low profile. “They are intentionally very stealthy,” Mitchell Mutz, an entrepreneur partner at Vivo Capital, one of RiboX’s investors, told Endpoints News . “There’s a reason it’s flown under the radar: It’s not based in Cambridge, Massachusetts.” The pharmaceutical industry is increasingly looking to China as a source of new drugs that can compete on a global scale. And RiboX is among a growing number of companies that appear to be outpacing their US counterparts in pushing the needle on genetic technologies. “I don’t really see American biotech as competitive anymore,” said R. Alexander Wesselhoeft, a co-founder of the circular RNA startup Orna Therapeutics and currently director of RNA Therapeutics Core at Mass General Brigham. RiboX CEO Weiyi Zhang declined multiple interview requests. According to PitchBook and LinkedIn profiles of people associated with the company, RiboX has raised $110 million, but Mutz and Zhang would not comment on that figure. “Since day one of RiboX, I have decided to focus on science and program development, and stay below the radar as much and as long as we can,” Zhang wrote in an email. The Boehringer Ingelheim Venture Fund confirmed to Endpoints that it is also an investor in RiboX but didn’t respond to additional questions. Qiming Venture Partners includes the startup in its portfolio on its website. Eisai Innovation, Lilly Asia Ventures and Temasek are also investors in the startup, according to Mutz, who has been on the startup’s board since last summer. Eisai, Lilly and Qiming did not respond to requests for comment, and a spokesperson for Temasek would not confirm or deny if it was an investor. Moderna and other mRNA developers have said the messenger molecule can be used to deliver instructions for practically any therapeutic protein into the body. But the linear strings of mRNA used in Covid-19 vaccines are short-lived. Those quick bursts of protein expression work well enough for a vaccine, but have constrained their use as therapies for chronic diseases. Circular RNA provides an alternative. Several lab studies have shown that when the loose ends of mRNA are strung together, the resulting circular molecule is more stable. Several Cambridge-based companies — Orbital Therapeutics, Orna Therapeutics and Sail Biomedicines — have raised large amounts of capital to develop circular RNA therapies that allow cells to pump out therapeutic proteins for weeks instead of days. ​​ Sail Biomedicines , once viewed as “ Moderna 2.0 ,” is perhaps the biggest bet on circular RNA therapies with $750 million in funding. MIT spinout Orna Therapeutics is the US biotech that’s farthest along, with plans for clinical trials in 2026 using circular RNA for in vivo immune cell therapies. Sail and Orbital have not announced clinical trial plans yet. RiboX said that it treated the first patient with its circular RNA therapy in early March. The RNA encodes a water channel called human aquaporin 1. RiboX hopes the protein will increase saliva production and treat dry mouth in people whose salivary glands have been damaged from radiation used to treat head and neck cancer. A single dose of the therapy boosted saliva flow for roughly four weeks in animal models, according to the company’s press release. While many Chinese biotech companies often focus their initial clinical efforts in China, RiboX got FDA clearance to test its therapy in the US. The company has an office in Princeton, NJ to oversee the clinical trial , which is underway at the University of Iowa. Henry T. Hoffman, a professor of otolaryngology and radiation oncology at the university who is leading the study, declined an interview request and referred questions to RiboX. Mutz said that injecting circular RNA in or near the salivary glands helped overcome one of the biggest challenges for any RNA medicine: delivering it to the right part of the body. “They didn’t necessarily want to go to an organ that was hard to target,” Mutz said. “So there is something to be said for not trying to solve everything at once.” RiboX is based on the work of RNA biologist Ling-Ling Chen at the Shanghai Institute of Biochemistry and Cell Biology in China and lipid nanoparticle researcher Dan Peer at Tel Aviv University. Neither responded to interview requests. Zhang, the company’s CEO and co-founder, previously led Boehringer Ingelheim’s External Innovation Hub China in Beijing. “Because their academic founders have been doing this for a long time, they weren’t so far from having something clinical when they started,” Mutz said. And, he added, that the RiboX investment came at a “reasonable price” and not with a “super high valuation” like its US competitors. There are very few public details on RiboX’s technology, but based on the company’s website and publications from RiboX founders, Wesselhoeft said that it looks like “the technology that everyone else is using, which is essentially MIT and Orna’s technology.” Zhang said in an email that the comparison to Orna’s technology was “false” and that the company’s “research and innovation are original, proprietary, and well protected,” she wrote. Mutz said that RiboX’s intellectual property with “predated” or “was differentiated enough” from Orna and other US companies for Vivo Capital to be comfortable with the investment. He also emphasized that RiboX’s ability to physically make circular RNA, a potential bottleneck in moving from the lab bench to the clinic, was where the startup “really shined.” “They had a circularization technology that gave them a good yield so that this would be scalable and manufacturable,” Mutz said. “Professors don’t often think about that stuff. And this is exactly where academic spinouts go to die. But the company always articulated this from day one.”

PRINCETON, NJ, USA I March 9, 2025 I RiboX Therapeutics Ltd. (RiboX), a pioneering biopharmaceutical company, focused on discovering and developing fully engineered circular RNA therapeutics, today announced that the first patient was dosed last week in its first-in-human (FIH) Phase I/IIa clinical trial (SPRINX-1) evaluating the safety and efficacy of RXRG001 in patients with radiation-induced-xerostomia (RIX) and hyposalivation. Xerostomia and hyposalivation are common side effects of radiation therapy in head and neck cancer (HNC) patients. Radiation therapy 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. There is a significant unmet medical need to develop a new treatment for xerostomia and hyposalivation. “Patients suffering radiation-induced xerostomia face a need for new therapeutic options. RXRG001 introduces an innovative approach offering hope for my patients. 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.”, commented Principal Investigator, Henry T. Hoffman, MD, MS, FACS, Professor, Otolaryngology and Editor, Iowa Head and Neck Protocols of University of Iowa. “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 of 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.” “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.” Yizhen Xu, MD, PhD, Chief Medical Officer of RiboX stated. About RXRG001 RXRG001 is a proprietary product developed using innovative circular RNA technology. In recent years, circular RNA has emerged as the next generation RNA 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 membranes), encapsulated in lipid nanoparticles (LNPs). RXRG001 is anticipated to increase saliva production by restoring water permeability via overexpression of hAQP1, therefore it alleviates dry mouth symptoms.  Non-clinical studies have 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. RXRG001 is the first-ever circular RNA therapy to receive FDA IND clearance back on October 25th, 2024. About RiboX Therapeutics RiboX is a globally operated biotech, dedicated to discovering and developing fully engineered circular RNA therapeutics, cofounded by Drs. Ling-Ling Chen, Dan Peer and Weiyi Zhang in 2021.  The company has operations in Princeton, NJ, USA, Rehovot, Israel and Shanghai, China. Circular RNA therapy is a novel modality, which is considered as the next generation RNA therapy. Compared to mRNA, circular RNA has a covalently closed single-stranded RNA structure that confers superior stability, lowers immunogenicity, and tunable protein expression, subsequently overcoming the current limitations of mRNA therapeutics and realizing the full potential of RNA medicines. RiboX’s pipeline spans various therapeutic areas, including radiation-induced xerostomia, monogenic rare diseases, autoimmune diseases, and metabolic diseases. RiboX is committed to pioneering innovative research in next-generation RNA therapies, with a vision to improve the quality of life for patients worldwide. For further details of the clinical trial, please visit: For further company information, please visit: https://www.riboxtx.com Media contact: bd@ribox-tx.com SOURCE: RiboX Therapeutics

PRINCETON, NJ, USA I October 25, 2024 I 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.” About RiboX Therapeutics RiboX is a globally operated biotech, dedicated to discovering and developing fully engineered circular RNA therapeutics, cofounded by Drs. Ling-Ling Chen, Dan Peer and Weiyi Zhang in 2021.  The company has operations in Princeton, NJ, USA, Rehovot, Israel and Shanghai, China. Circular RNA therapy is a novel modality, which is considered as the next generation RNA therapy. Compared to mRNA, circular RNA has a covalently closed single-stranded RNA structure that confers superior stability, lowers immunogenicity, and tunable protein expression, subsequently overcoming the current limitations of mRNA therapeutics and realizing the full potential of RNA medicines. RiboX has developed proprietary plug-and-play circular RNA drug design and engineering, combined with novel LNPs platforms and robust manufacturing capabilities. These innovative technologies provide support for the clinical development of circular RNA therapeutics. RiboX’s pipeline spans various therapeutic areas, including radiation-induced xerostomia, monogenic diseases, autoimmune diseases, and vaccines. RiboX is committed to pioneering innovative research in next-generation RNA therapies, with a vision to improve the quality of life for patients worldwide. For further information, please visit: https://www.riboxtx.com SOURCE: RiboX Therapeutics