Ruzinurad

Courtesy ThamKC/Getty Images Incidence of gout has increased globally during the past quarter-century, spurring the development of new, more effective therapies aimed at chronic gout. "Gout is the most common inflammatory arthritis in the world, and existing treatments rarely achieve target serum urate levels,” said Shunqi Yan, Ph.D., founder and chief operating officer of Arthrosi Therapeutics in an interview with BioSpace. “As patients continue to be undertreated with current therapies, monosodium urate crystals (called tophi) continue to accumulate in the joints and tendons, worsening flares, joint erosions and disability.” An aging, more sedentary population is one of the reasons for the uptick, along with purine-rich diets (such as red and organ meats, anchovies, sardines, mussels, scallops, trout and tuna, as well as alcoholic beverages and drinks high in fructose). Genetic associations may also be involved. These conditions each can cause uric acid levels to increase. Inhibiting and Degrading Uric Acid Scientists are exploring three broad ways to address this. The first tries to inhibit the production of uric acid, degrade it or enhance its ability to leave the body. “One category of treatments uses xanthine oxidase inhibitors, notably allopurinol, to reduce the production of uric acid in your body,” said Roy Wu, SVP of global business development for Atom Bioscience. Allopurinol is the standard of care, yet “Its efficacy is only about 40 to 45 percent,” Wu said. Its safety pro improvement, too. “It’s not very well tolerated, causing a skin reaction (Stevens-Johnson Syndrome) and GI problems. It also requires titration over a long period of time, which means doses can’t be adjusted rapidly," he noted. While a few companies are investigating iterations of xanthine oxidase inhibitors, a scan of ClinicalTrials.gov shows more activity focused on other approaches. Metabolizing Uric Acid Synlogic, for one, is working to metabolize uric acid in the GI tract with an engineered strain of a probiotic bacteria, said Dave Hava, Ph.D., chief scientific officer. “We hypothesize there is a significant gut component to uric acid metabolism – that uric acid can come from the diet through purine metabolism, but that it also could recirculate in the systemic circulation into the GI tract and be secreted back out, in a kind of loop. “We hypothesized that if we could design a bacteria that encounters uric acid in the GI tract, breaks it down into something non-toxic and prevents its reabsorption into systemic circulation, it could ultimately lower uric acid levels in the plasma,” Hava explained. Preclinical data from the prototype strain support that hypothesis. Non-human primate studies show the engineered strain Synlogic designed is active and can reduce systemic levels of uric acid. “We anticipate releasing more preclinical data on SYNB2081 later this year,” Hava said. Synlogic worked with Ginkgo Bioworks to design the prototype probiotic strain, essentially programming it to be effective under the conditions prevalent in gout. “Biology is fundamentally programmable,” said Patrick Boyle, Ph.D., head of Codebase, at Ginkgo Bioworks. “If you think about the substrate of biology that we’re engineering, we’re rewriting genetic code. Many of the same principles apply between digital code and software code. While biology is infinitely more complex than computer code, changing an A to a T affects how the cell reads that DNA code and changes its behavior.” Ginkgo used that approach with Synlogic to design organisms for a particular purpose. Another company, Allena Pharmaceuticals, has Fast Track designation for its orally-absorbed enzyme to treat gout and chronic kidney disease. When kidneys are impaired, uric acid is eliminated through the GI tract, so ALLN-346 degrades urate there in a way that prevents it from being absorbed systemically. Allena completed enrollment of a Phase IIa outpatient study 202 in July. Results have not been released. Urate Transporter 1 Inhibitors A third approach is to cause the system to excrete uric acid more efficiently. “About 85% of gout patients have a problem eliminating enough uric acid,” Yan said. A urate transporter 1 (URAT1) inhibitor, therefore, could fill a large unmet need. “There is an increasing body of evidence that URAT1 inhibitors may slow the progression of chronic kidney disease and also may have cardiovascular benefits,” he noted. To that end, Arthrosi is developing AR882 to normalize uric acid excretion through the kidney. This would reduce circulating levels of uric acid throughout the body as well as the formation of monosodium urate crystals. The goal is to reduce serum urate levels below the 6mg/dL needed for disease control and, ideally, below 5mg/dL. AR882 “has been shown to be well-tolerated in clinical trials…and is the only oral therapy evaluating the tophi reduction potential in a Phase II study,” Yan said. Arthrosi completed enrollment of more than 120 patients with chronic gout in a global Phase IIb study being conducted at 24 sites in the United States, Australia and Taiwan. The three-month study will evaluate dosage. In the earlier Phase IIa study, a 50 mg dose of AR882 reduced serum levels to below 5mg/dL in 93 percent of patients, whereas a 75 mg dose reduced levels below 4mg/dl in 88 percent of patients, suggesting it may also succeed in reducing flares. Atom Bioscience is also concentrating on uric acid excretion. “ABP-671 is a URAT1 inhibitor, which helps block the reabsorption of uric acid back into the body through the kidney and thus to excrete uric acid,” Wu said. “This is a more direct approach to reducing uric acid from the body than reducing its production.” Early studies showed a nearly 30 percent reduction in uric acid during the first day of treatment, which Wu called significant. Atom is finalizing the protocols for a Phase IIb/III study for chronic gout that likely will begin in 2023. It’s a six-month treatment and is expected to take six to nine months to enroll, so a readout in mid-2024 seems likely. Atom is thinking of ABP-671 as a possible first-line monotherapy, Wu said.

MIAMI, Oct. 03, 2022 (GLOBE NEWSWIRE) -- Urica Therapeutics, Inc. (“Urica” or the “Company”) (formerly known as UR-1 Therapeutics, Inc.), a Fortress Biotech Inc. (Nasdaq: FBIO) (“Fortress”) subsidiary company focused on the development and commercialization of pharmaceutical products to treat gout and chronic kidney disease, today announced the appointments of Jay D. Kranzler, M.D., Ph.D., as Chairman and Chief Executive Officer and Vibeke Strand, M.D., MACR, FACP, Adjunct Clinical Professor, Division of Immunology/Rheumatology, Stanford University, to its Board of Directors. Lindsay A. Rosenwald, M.D., Fortress’ Chairman and Chief Executive Officer and Board Member of Urica, said, “We are pleased to welcome Jay as Chairman and Chief Executive Officer of Urica and Vibeke to the Board. Jay has been an important advisor to Fortress over the past few years. His extensive experience across all aspects of drug development will add significant value as Urica advances dotinurad for the treatment of gout and possibly other hyperuricemic indications including chronic kidney disease and heart failure. We are equally thrilled to add Vibeke to the Board given her vast knowledge in rheumatology. Her clinical research and regulatory strategy expertise will be invaluable as dotinurad continues to progress through clinical development. We look forward to the anticipated announcement of topline data from our Phase 1 trial in the second half of 2022.” Dr. Kranzler has been a Founder, Chief Executive Officer, Board Member and Advisor to leading life science companies for over 30 years. Dr. Kranzler joins Urica to guide and expedite the development of its lead product candidate, dotinurad, a potential best-in-class urate transporter (URAT1) inhibitor that is currently in Phase 1 clinical trials and positioned for the treatment of gout in the United States. Dotinurad (URECE® tablet in Japan) was approved in Japan in 2020 as a once-daily oral therapy for gout and hyperuricemia. Dotinurad was efficacious and well-tolerated in more than 500 Japanese patients treated for up to 58 weeks in Phase 3 clinical trials. “I am gratified to be extending my engagement with Fortress to lead its newest subsidiary and manage development of such a promising technology. With an experienced team, we are well positioned to replicate the exceptional clinical efficacy and safety pro dotinurad has already demonstrated in Japanese trials and clinical use,” said Dr. Kranzler. “With success, we hope to expand treatment options for the nearly 10 million patients suffering from gout in the Unites States, in addition to the 10 million patients in our other licensed territories, and possibly explore efficacy in other hyperuricemic indications, while creating value for shareholders.” Dr. Kranzler has served in operational and consulting capacities for multiple large pharmaceutical companies, small biotechnology companies, investment banks and investors. He has developed drugs, medical devices and diagnostics, and is an inventor on multiple key patents. Dr. Kranzler serves as an Adjunct Professor at New York University Stern School of Business and at the New York University Langone School of Medicine. Previously, Dr. Kranzler was Vice President and Global Head of External R&D Innovation and Worldwide R&D Strategic Investments at Pfizer. His entrepreneurial career includes his role as Founder and Chief Executive Officer of Cypress Bioscience, where he was credited for the development of Savella™ (milnacipran) for the treatment of fibromyalgia. He also served as Chief Executive Officer of Cytel Corporation and was a Founder of Perception Neuroscience, which was acquired by ATAI Life Sciences. Dr. Kranzler started his career at McKinsey & Company where he was a key member of the team that established the firm’s pharmaceutical practice. He is currently a Board Member of Avenue Therapeutics (Nasdaq: ATXI), Baergic Bio, Pastorus, Navitas and ImmunoBrain Checkpoint. Dr. Kranzler graduated from Yale University School of Medicine with M.D. and Ph.D. degrees with a focus in psychopharmacology. Dr. Vibeke Strand has served as an adjunct clinical professor in the Division of Immunology and Rheumatology at Stanford University School of Medicine since 1993. For several decades, she has led a consulting practice offering clinical research and regulatory strategy expertise to pharmaceutical and biotech with a focus on translating basic research into rational design of randomized controlled trials, evaluation of their results and defense of novel products in rheumatology to the U.S. Food and Drug Administration and European Medicines Agency. She has participated in the successful development of DMARDs, biologics and JAK inhibitors in an array of rheumatoid conditions and biosimilars. Dr. Strand has authored more than 500 publications, is a Fellow of the American College of Physicians, Master of the American College of Rheumatology and member of the Cosmos Club. She received her B.A. from Swarthmore College and her M.D. from University of California San Francisco School of Medicine. “I look forward to working with Urica and my fellow board members as we advance the development of dotinurad, an innovative therapy that holds the potential to address the needs of multiple patient populations requiring more effective treatment,” said Dr. Strand. About Dotinurad In May 2021, Fortress announced an exclusive license agreement between its subsidiary, Urica Therapeutics, Inc. (formerly UR-1 Therapeutics, Inc.), and Fuji Yakuhin Co. Ltd. to develop dotinurad in North America and Europe. Dotinurad is a potential best-in-class urate transporter (URAT1) inhibitor for gout and possibly other hyperuricemic indications including chronic kidney disease and heart failure. It can lower blood uric acid levels by selectively inhibiting URAT1 and uric acid reabsorption in the kidneys. Dotinurad (URECE® tablet) was approved in Japan in 2020 as a once-daily oral therapy for gout and hyperuricemia. Dotinurad was efficacious and well-tolerated in more than 500 Japanese patients treated for up to 58 weeks in Phase 3 clinical trials. Its efficacy demonstrated non-inferiority to Febuxostat, which has a black box warning for increased risk of cardiovascular death, and dotinurad was well-tolerated with apparent low safety risk and drug interaction.1,2,3 Over 1,000 Japanese patients have been treated safely with dotinurad in clinical trials. Also, dotinurad is currently in Phase 3 clinical trials in China. About Gout Gout is a serious, progressive and debilitating inflammatory arthritis caused by deposits of uric acid crystal in and around the connective tissue of joints, tendons and the kidneys. There are nearly 20 million diagnosed patients with gout in the US, Europe and Canada as of 2021,4,5,6 and it is estimated that two to three million U.S. patients are unsatisfied with their urate-lowering therapy and their serum uric acid levels remain inadequately controlled.7,8 About Urica Therapeutics Urica Therapeutics, Inc. (“Urica”) is a clinical-stage biopharmaceutical company that focuses on the development and commercialization of pharmaceutical products to treat gout and chronic kidney disease. Urica acquired the rights to develop and commercialize Dotinurad, a potentially best-in-class URAT1 inhibitor, in the United States, United Kingdom, European Union and Canada from Fuji Yakuhin. Dotinurad has been approved to treat gout and hyperuricemia in Japan and is currently in a Phase 1 clinical trial in the United States. Urica was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). About Fortress Biotech Fortress Biotech, Inc. (“Fortress”) is an innovative biopharmaceutical company focused on acquiring, developing and commercializing high-potential marketed and development-stage drugs and drug candidates. The company has nine marketed prescription pharmaceutical products and over 30 programs in development at Fortress, at its majority-owned and majority-controlled partners and subsidiaries and at partners and subsidiaries it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise to further expand the company’s portfolio of product opportunities. Fortress has established partnerships with some of the world’s leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including AstraZeneca plc, City of Hope, Fred Hutchinson Cancer Research Center, St. Jude Children’s Research Hospital, Nationwide Children’s Hospital and Sentynl Therapeutics, Inc. For more information, visit . Forward-Looking Statements This press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. As used below and throughout this press release, the words “we”, “us” and “our” may refer to Fortress individually or together with one or more partner companies, as dictated by context. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs, ability to generate shareholder value, ability of our products to receive necessary approvals, including FDA, ability of our products and therapies to help patients and any other statements that are not historical facts. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; risks relating to the timing of starting and completing clinical trials, including disruptions that may result from hostilities in Europe; our dependence on third-party suppliers; risks relating to the COVID-19 outbreak and its potential impact on our employees’ and consultants’ ability to complete work in a timely manner and on our ability to obtain additional financing on favorable terms or at all; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Company Contacts: Jaclyn Jaffe and Bill Begien Fortress Biotech, Inc. (781) 652-4500 ir@fortressbiotech.com Media Relations Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com References Clin Exp Nephrol. 2020 Mar;24(Suppl 1):71-79. Clin Exp Nephrol. 2020 Mar;24(Suppl 1):62-70. Clin Exp Nephrol. 2020 Mar;24(Suppl 1):80-91. Rheumatology (Oxford). 2019 Dec 1;58(12):2177-2180. Semin Arthritis Rheum. 2017 Feb; 46(4): 451–456. GlobalData. Gouty Arthritis (Gout): Competitive Landscape in 2021. Arthritis Rheumatol. 2019 Jun; 71(6): 991–999. J Rheumatol. 2016 Oct;43(10):1897-1903.