Arthrosi Announces AR882, a Potent and Long-Acting Uricosuric Agent for Gout, Advancing to Phase II Clinical Trials

Dr. Ye Litian, Founder of Arthrosi Therapeutics, boasts a distinguished track record that serves as the company’s hallmark credential. From his early role as Chief Scientist at Dow-Elanco to Drug Development Director at Valeant, Dr. Ye has held senior leadership positions at globally renowned pharmaceutical companies, including Vice President of Translational Science at AstraZeneca and Ardea, and Vice President of R&D at Roche and Ignyta. As a leading figure in new drug development, Dr. Ye has achieved remarkable success, bringing six novel therapeutics targeting diverse indications to market in Europe, the United States, and Japan.

This portfolio includes Cesamet, a novel antiemetic acting on the nervous system; retigabine, a new-generation antiepileptic drug; RDEA119, an anti-tumor kinase inhibitor in Phase II clinical trials; entrectinib, a targeted anti-cancer therapy; and lesinurad, the first novel combination drug for gout. Notably, entrectinib, a rising star in targeted oncology therapies, was developed by Ignyta, which was acquired by Roche for $1.7 billion in 2018. Entrectinib was the first drug to simultaneously submit new drug applications in the United States, Europe, and Japan (“three-crown” approval). It filed for regulatory approval in late 2018 and has since secured fast-track approvals in Japan and the United States in June and August of this year, respectively.

Although Dr. Ye Litian has achieved remarkable success in the field of oncology, he remains deeply committed to advancing treatments for gout. Lesinurad, the first uricosuric agent for gout approved by the U.S. Food and Drug Administration (FDA) in four decades, was developed under Dr. Ye’s leadership at Ardea Biosciences. The company was subsequently acquired by AstraZeneca for $1.2 billion, and lesinurad gained regulatory approval in the United States in 2015 and in the European Union in 2016, becoming the most recently launched medication for gout.

The primary cause of gout is hyperuricemia, which leads to the deposition of urate crystals in joints and soft tissues. One of the causes of elevated uric acid levels is impaired excretion due to excessive renal reabsorption of uric acid. Lesinurad effectively inhibits the transporters responsible for uric acid reabsorption, thereby lowering serum uric acid levels and demonstrating favorable efficacy at adequate drug concentrations.

Dr. Ye Litian candidly acknowledged that while lesinurad has its merits, it also has drawbacks; compared to an ideal therapeutic agent for gout, he holds higher expectations. The drug’s inherent chemical structure results in excessively rapid renal excretion, leading to insufficient duration of inhibition of urate transporters. This inefficient blockade of uric acid reabsorption fails to effectively eliminate uric acid from the body, with clinical data showing a half-life of less than 12 hours. Furthermore, the relatively high urinary drug concentration per unit time increases renal burden, thereby elevating the risk of renal impairment. This limitation restricts lesinurad to use only in combination therapy. Consequently, Dr. Ye has been seeking a next-generation, long-acting, and safe medication for gout to achieve highly effective treatment.

Meanwhile, Dr. Yan Shunqi, who has made significant achievements in new drug development, has also been closely following the field of gout. The two individuals, sharing not only common aspirations but also a history as former colleagues, formed a highly synergistic partnership that spurred the exploration of new collaborative opportunities. Dr. Yan previously served as Director of Computational Chemistry and Structural Biology at ChemPartner, and as Chief Scientist at U.S. biotechnology companies such as Ignyta and Schrödinger. He holds over 200 patent applications worldwide and has contributed to the invention of seven clinical-stage drugs, including two FDA-approved first-in-class anti-tumor agents, Idhifa and Ivosidenib, as well as Mitapivat, a first-in-class investigational drug in Phase III clinical trials for the treatment of hemolytic anemia. Notably, Idhifa received the Prix Galien Award in 2018, the highest honor in the pharmaceutical and biomedical industries, often referred to as the “Nobel Prize of Medicine.”

After months of iterative synthesis and literature review, followed by a series of experimental validations targeting gout mechanisms, a compound with the same mechanism of action as lesinurad but a completely different chemical architecture emerged, named AR882.

New drug development is the specialty of the two PhDs. Whether they are starting their own ventures or working for pharmaceutical companies, new drug development always adheres to the same rigorous and pragmatic scientific theories and experiments, which they handle with ease.

Arthrosi Therapeutics was established in early 2018 and successfully raised $4 million in Series A financing, with its headquarters located in California, USA. Through efficient capital utilization, the company successfully completed all preclinical studies, filed for Phase I clinical trials in Australia by the end of 2018, and obtained approval. This progress and data attracted numerous investors, enabling the successful completion of an $11 million Series B financing round by the end of 2018. The rapid fundraising pace not only reflects the capital market’s recognition of Arthrosi Therapeutics but also underscores the demand from patients and the market for promising drugs such as AR882.

As a seed and Series B investor in Arthrosi Therapeutics, Viva Biotech has also had the privilege of participating in the company’s early-stage R&D processes. Dr. Zhi-Xiong Ye, Chief Scientific Officer of Viva Biotech, stated, “Gout and its related conditions continue to affect the lives of millions of people worldwide. Dr. Li-Tian Ye was the lead scientist in the development of lesinurad, the latest medication for gout treatment. Together with Dr. Shunqi Yan, he has identified a novel molecule with significantly high efficacy and safety. We are delighted to have this opportunity to collaborate, supporting Dr. Ye and Dr. Yan’s research on uric acid excretion promoters through Viva Biotech’s ‘Service-for-Equity’ model under the VivaBioinnovator platform, thereby addressing the needs of more gout patients.”

As a next-generation uric acid excretion promoter, AR882 overcomes the shortcomings of lesinurad. It binds long-acting to urate transporters, prolonging the duration of inhibition, with clinical results demonstrating efficacy lasting up to 24 hours. Meanwhile, its around-the-clock blockade of uric acid reabsorption does not increase renal burden, thereby avoiding nephrotoxicity. Dr. Ye Litian and Dr. Yan Shunqi are highly confident that the long-acting and safe profile of AR882 can effectively reduce the frequency of gout flares and dissolve tophi, positioning it as a promising candidate for the most effective serum uric acid-lowering agent in clinical practice.

Currently, AR882 has completed Phase I clinical trials, including single ascending dose (SAD), multiple ascending dose (MAD), and combination dosing with febuxostat. Phase II clinical trials are being prepared, and corresponding preclinical toxicology and safety studies are ongoing.

Arthrosi Therapeutics applied for clinical trial approval in November 2018 and obtained it in December of the same year. By August 2019, AR882 had successfully completed safety, pharmacodynamic, and pharmacokinetic trials in more than 70 healthy volunteers. Dr. Ye Litian revealed that the test results for AR882 were highly promising, as expected, and specific experimental data will be presented at a major conference in the United States by the end of this year.

Arthrosi is expected to advance AR882 into Phase II clinical trials in humans by the end of 2019. Furthermore, Arthrosi boasts a highly experienced and execution-driven team capable of effectively implementing its established clinical development plans.

For seasoned drug hunters Dr. Ye Litian and Dr. Yan Shunqi, there is confidence in successfully completing clinical trials and bringing the product to market to benefit patients. Dr. Ye Litian and Dr. Yan Shunqi candidly stated, “We are very familiar with the drug design and development process; we have gone through each step many times, and the numerous twists and turns encountered were within our expectations. However, we were quite anxious before seeing the clinical trial results. Once the data emerged, we found that AR882 performed even better than we had imagined.”

Dr. Ye Litian added, “Given AR882’s 24-hour sustained inhibitory effect, which provides round-the-clock coverage of uric acid reabsorption inhibition, I believe AR882 will become the ‘best in class’—the most efficacious gout medication among its peers.”

In addition to its core pipeline asset AR882, Arthrosi is also developing anti-tumor drugs, establishing a new R&D pipeline for oncology therapeutics, and collaborating with pharmaceutical companies in China and the United States.

Regarding the future of Arthrosi, Dr. Ye Litian stated, “The journey from drug development to market launch is a long and complex process, requiring an influx of fresh talent at every stage. In the later phases, large pharmaceutical companies with substantial financial resources hold a competitive advantage. As for the future of Arthrosi, we maintain an open mindset. Ideally, once AR882 completes Phase II clinical trials, we aim to bring it to market through collaboration with or acquisition by a major pharmaceutical company, thereby enabling patients to access highly effective treatments sooner.”

It is reported that Arthrosi has launched its Series B-1 financing round, aiming to raise $25 million to $30 million to advance further clinical trials of AR882.