Arthritis, Gouty

Health consequences of over active xanthine oxidase may accelerated PKD progressionCALGARY, Alberta, Aug. 20, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANUA), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to announce the acceptance of an abstract submitted to the American Society of Nephrology (the “ASN”). The abstract entitled "Xanthine oxidase in rats, mice and humans with polycystic kidney disease" was reviewed by the ASN review panel for scientific merit and novel discoveries. The study was conducted at the University of Colorado in the independent laboratory of Dr. Charles Edelstein and was sponsored by XORTX and will be presented during the Session Title: Genetic Diseases: Cystic - Therapeutic Investigations and Prognosis. About this study The xanthine oxidase (“XO”) enzyme is an essential enzyme within the uric acid pathway, and is required for the breakdown of purine nucleotides. Uric acid as well as reactive oxygen species released during the enzymatic reaction may also play a detrimental role in the circulatory system and within tissue during disease. Recent pioneering discoveries in rodent models of polycystic kidney disease (“PKD”) implicate over expression or over activity of XO. It is currently unknown if XO over expression or over activity in humans is associated with PKD or more rapid progression of disease. The aim of the study was to gain insight into whether increased XO activity results in cyst growth, XO activity was measured in PCK1 rats, PKD1RC/RC (RC) mice and 34 patients from the HALT-PKD Clinical study. The abstract outlines study results from mouse, rat and human studies of PKD. The purpose of the study was to gain an understanding of serum xanthine oxidase activity (XOa) in PKD during varied stages of disease and further to relate that activity to total kidney volume, and decline of glomerular filtration rate (GFR). The results of the study provide understanding of where aberrant purine metabolism in PKD tissue due to sources XO enzyme may contribute to circulating uric acid levels, expansion rate of kidney and cyst and functional GFR decline. Prior study results suggested over expression of XO in PKD kidney tissue may be a feature of cystic disease. XORTX will provide a further update on the results of the study during the first week of November. Dr. Allen Davidoff, CEO of XORTX, stated, “We are pleased to once again be presenting pioneering studies in PKD due to ADPKD at the American Society of Nephrology annual meeting during Kidney Week 2024 with this poster presentation. Most importantly, results of this study deepen our understanding of how increased serum uric acid or aberrant kidney tissue expression of XO contribute to accelerate injury using data from mouse, rat and human studies of PKD. The XRx-008 program continues to pioneer our understanding of how too much or too active xanthine oxidase may result in a health consequence in PKD.” About the American Society of Nephrology – Kidney Week ASN represents more than 21,000 kidney health professionals working to help people with kidney diseases and their families. (Source: https://www.asn-online.org/) The Kidney Week Conference is attended by approximately 10,000 other kidney professionals from across the globe at Kidney Week 2024 in Orlando, Florida. The world's premier nephrology meeting, Kidney Week provides participants with exciting and challenging opportunities to exchange knowledge, learn the latest scientific and medical advances, and listen to engaging and provocative discussions with leading experts in the field. (Source: https://www.asn-online.org/education/kidneyweek/American Society of Nephrology - Program and Abstracts) The Kidney Week program is available on the ASN website. Abstracts will be available on the ASN website by October 14, 2024. About ADPKD ADPKD is a rare disease that affects more that 10 million individuals worldwide.1,2 ADPKD is typically diagnosed based upon expansion of fluid-filled cysts in the kidneys. Over time, the increasing number and size of cysts can contribute to structural and functional changes to kidneys and is frequently accompanied by chronic pain which is a common problem for patients with ADPKD.3 Expansion of cysts is thought to compress healthy functioning tissue surrounding the cysts and contribute to further loss of kidney function, fibrosis, impaired nutrient exchange and impaired kidney function, accompanied later by end-stage renal disease.1 Health consequences of high uric acid have been reported to be increased in ADPKD individuals, including increased incidence of kidney stones5 and gout.6,7 For individuals with progressing ADPKD, treatment recommendations include anti-hypertensive treatment, dietary restrictions, and, for a limited percentage of suitable patients, pharmacotherapy.4 New, more broadly applicable therapies to effectively slow decline of kidney function in ADPKD are needed. References: Wiley C., Kamat S., Stelhorn R., Blais J., Analysis of nationwide date to determine the incidence and diagnosis of autosomal dominant polycystic kidney disease in the USA, Kidney Disease, 5(2): 107-117, 2019Bergmann C., Guay-Woodford L.M., Harris P.C., Horie S., Peters D.J., Torres V.E., Polycystic Kidney Disease, Nat Rev Dis Primers. 4(1): 50, 2018https://pkdcure.org/living-with-pkd/chronic-pain-managementGimpel C., Bergmann C., Bockenhauer D., et al., International consensus statement of the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people, Nat Rev Nephrol 15(11):713-726, 2019Torres VE, et al, The association of nephrolithiasis and autosomal dominant polycystic kidney disease, Am J Kidney Dis, 1988, vol 11, 318-325Newcombe, DS. Letter Gouty Arthritis and polycystic kidney disease, Ann Intern Med, 1973 vol 79, pg 605Rivera JV Martinez, et al, Association of hyperuricemia and polycystic kidney disease, Bol Asoc Med P R, 1965 vol 7 251-263 About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with two clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; and 2) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications to improve the quality of life and future health of patients. Additional information on XORTX is available at www.xortx.com. For more information, please contact: Allen Davidoff, CEONick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727nick@alpineequityadv.com or +1 617 901 0785 Kim Golodetz, LHA Investor Relations kgolodetz@lhai.com or +1 212 838 3777 Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein. Forward Looking Statements This press release contains express or implied forward-looking statements pursuant to applicable securities laws. These forward-looking statements include, but are not limited to, the Company's beliefs, plans, goals, objectives, expectations, assumptions, estimates, intentions, future performance, other statements that are not historical facts and statements identified by words such as "expects", "anticipates", "intends", "plans", "believes", "seeks", "estimates" or words of similar meaning. These forward-looking statements and their implications are based on the current expectations of the management of XORTX only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Such risks, uncertainties, and other factors include, but are not limited to, our ability to obtain additional financing; the accuracy of our estimates regarding expenses, future revenues and capital requirements; the success and timing of our preclinical studies and clinical trials; the performance of third-party manufacturers and contract research organizations; our plans to develop and commercialize our product candidates; our plans to advance research in other kidney disease applications; and, our ability to obtain and maintain intellectual property protection for our product candidates. Except as otherwise required by applicable law and stock exchange rules, XORTX undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting XORTX is contained under the heading “Risk Factors” in XORTX’s Annual Report on Form 20-F filed with the SEC, which is available on the SEC's website, www.sec.gov (including any documents forming a part thereof or incorporated by reference therein), as well as in our reports, public disclosure documents and other filings with the securities commissions and other regulatory bodies in Canada, which are available on www.sedarplus.ca.

— Continued treatment with AR882 demonstrated safe, efficacious and sustained reduction in sUA at 12 months — — AR882 achieved deep and durable tophus and crystal volume dissolution at 12 months — SAN DIEGO, June 14, 2024 /PRNewswire/ -- Arthrosi Therapeutics, Inc., a late-stage biotechnology company developing a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and tophi in patients with gout, today announced new positive clinical data from its phase 2 AR882-203 study in patients with tophaceous gout. These data are being presented as poster presentations at the European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology, being held June 12-15 in Vienna, Austria. "We are excited to share new data from our Phase 2 trial of AR882 highlighting its long-term durability of effect and strong safety profile, further building on the body of evidence supporting AR882 as a potentially best-in-class treatment for patients with gout," said Arthrosi's Chief Medical Officer Robert T. Keenan, MD, MPH, MBA. "There remains a significant unmet need for patients with tophaceous gout, a disease marked by chronic pain and significantly diminished functionality. This new 12-month data reinforce the promising findings from the initial 6-month treatment period of the Phase 2 trial, demonstrating safe and robust SUA lowering as well as deeper and durable tophus and crystal volume dissolution at 12 months. Based on the favorable therapeutic profile observed to date, we believe AR882 has the potential to reduce debilitating symptoms and significantly improve treatment outcomes for patients with gout. We are currently advancing AR882 in a pivotal Phase 3 program and look forward to initiating the second confirmatory phase 3 study later this year." New Clinical Data for AR882, Arthrosi's URAT1 Inhibitor In a poster tour presentation, Dr. Keenan will highlight new 12-month clinical data from the company's phase 2 trial in patients with chronic gouty arthritis building upon AR882's promising safety and efficacy profile and further validating its durability of response. The phase 2, randomized, open-label, global trial recruited 42 patients with at least one subcutaneous tophus. The patients were randomized equally into three treatment groups to receive a once daily dose of AR882 75 mg, AR882 50 mg + allopurinol or allopurinol up to 300 mg. At the end of 6 months, the allopurinol monotherapy group had AR882 75 mg added, while the other two groups continued the same therapy. The data showed: Both the AR882 75 mg and the AR882 50 + allopurinol groups demonstrated a persistent and sustained decrease in sUA throughout the 12 months. The average baseline sUA level ranged between 9.1-9.6 mg/dL across groups. At 3 months, median patient sUA levels were reduced to 4.5, 4.7, and 6.1 mg/dL for AR882 75 mg, AR882 50 mg + allopurinol and allopurinol groups, respectively. Notably, at 12 months, sUA levels for all groups further decreased to 3.9, 4.4 mg/dL and 4.0 mg/dL for the AR882 75 mg, AR882 50 mg + allopurinol and AR882 75 mg + allopurinol groups, respectively. During the 6-month extension phase, complete tophus resolution of at least 1 target tophus measured by digital caliper was seen in 35.7% (5/14) for the AR882 75 mg group and 36.4% (4/11) for the AR882 75 mg + allopurinol group. From baseline to Month 6, AR882 75 mg alone or in combination with allopurinol showed reduction of total urate crystal volume of -7.5 cm3 and -10.6 cm3, respectively. AR882 75 mg as monotherapy was further evaluated through months 6 to 12 and demonstrated a sustained crystal volume reduction of -13.3 cm3. In patients with significant baseline crystal volume of ≥5.0 cm3 AR882 75 mg demonstrated a sustained -26.4 cm3 reduction at 12 months. AR882 was well tolerated throughout 12-month chronic treatment both as a monotherapy and in combination with allopurinol. Drug-Drug Interaction Data for AR882 In a second poster presentation, Litain Yeh, Ph.D., Chief Executive Officer of Arthrosi, will discuss in vitro and clinical data supporting AR882's potential to be safely administered to gout patients with various concomitant medications and comorbid conditions including diabetes, hypertension and hyperlipidemia. The data show: In vitro assessments indicated that AR882 exhibited no drug-drug interactions (DDI) with key renal, hepatic and gastrointestinal transporters as substrate or inhibitor at the relevant clinical concentration. AR882 had no inhibitory effect on any transporters except for breast cancer resistance protein (BCRP), which plays an important role in the transport of urate, a key component in gout development. Based on these preclinical findings, Arthrosi conducted a clinical DDI study of AR882 as an inhibitor of BCRP. Sulfasalazine, a clinical substrate of BCRP and a commonly used drug in autoimmune and rheumatic diseases, was selected for the study. Co-administration of AR882 75 mg with sulfasalazine produced no clinically relevant alterations in the pharmacokinetics (Cmax and AUC) of sulfasalazine, suggesting no clinically significant BCRP-mediated DDI. Details for the poster presentations are as follows: Title: AR882, a Novel and Selective URAT1 Inhibitor, Significantly Reduced Tophi in Patients with Chronic Gouty Arthritis: Results of 12-month Outcome from a Global Trial using Digital Caliper Measurements and Dual Energy Computed Tomography Session Title: Clinical Poster Tours: Gout treatment in 2024 Presenting Author: Robert Keenan, M.D., Chief Medical Officer of Arthrosi Therapeutics Abstract Number: POS0268 Date/Time: Friday, June 14 / 9:30am-10:30am CEST Title: AR882, a Selective URAT1 Inhibitor, Exhibits No Drug-Drug Interactions with Key Renal, Hepatic, and GI Transporters Presenting Author: Litain Yeh, Ph.D, Co-Founder and Chief Executive Officer of Arthrosi Therapeutics Abstract Number: POS0935 Date/Time: Friday, June 14 / 9:30am-10:30am CEST Both poster presentations will be available in the "Publications" section of Arthrosi's website: . About the AR882-203 Phase 2 Study The Phase 2 study of AR882 in patients with tophaceous gout was a six-month, 1:1:1 randomized, global, placebo-controlled study of 42 patients with subcutaneous tophi. The mean baseline sUA among the participants ranged between 9.1-9.6 mg/dL. In the study, patients received a once daily dose of either 75 mg AR882, 50mg AR882 + allopurinol, or allopurinol up to 300mg. Serum uric acid levels (< 6, <5, <4, or <3 mg/dL) were evaluated monthly through month 6, and safety and tolerability were assessed throughout the study. Tophi measurements with calipers were completed every 4 weeks for 6 months. Patients were also imaged using Dual-Energy Computed Tomography (DECT), DECT a specialized imaging technique that is able to differentiate and identify uric acid crystals in the joints and soft tissue, allowing for quantifying uric acid crystals and tophi at baseline and 6 months. The primary efficacy endpoint was sUA change at 3 months. Secondary endpoints included complete resolution of at least one target tophus with no new tophi and no tophus showing progression. Safety assessments, including vital signs and electrocardiograms, were collected throughout the study. The trial also included a 6-month extension period designed to evaluate longer-term patient outcomes. About Gout: In the U.S., an estimated 13 million individuals are diagnosed with gout. Gout is a form of inflammatory arthritis that can significantly diminish mobility, functionality, and overall quality of life. Gout emerges from the crystallization of uric acid within the joints and soft tissue, instigating painful flare-ups and chronic symptoms. The kidneys play a pivotal role in the process, as they are responsible for filtering out and excreting uric acid from the body. In over 90% of gout patients, underexcretion of uric acid results in the imbalanced and elevated sUA levels that can lead to the deposition of uric acid crystals. It's essential to monitor and manage sUA levels as part of comprehensive gout treatment and prevention strategies. About Arthrosi: Arthrosi Therapeutics, Inc., headquartered in San Diego, CA, is focused on developing AR882, a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and Tophi in patients with gout. Gout remains a large and growing market with ~ 13M patients in the U.S. alone, ~2M of which have tophaceous gout. AR882 has demonstrated encouraging efficacy and safety compared to SOC in Phase 2 studies as well as impressive results in achieving complete resolution of tophi in a Phase 2b study. Arthrosi anticipates initiating pivotal phase 3 program in early 2024. Media Contact: Shunqi Yan, PhD Founder & Chief Operating Officer [email protected] Investor Contact: Precision AQ Alex Lobo 212-698-8802 [email protected] SOURCE Arthrosi Therapeutics

SAN DIEGO, May 30, 2024 /PRNewswire/ -- Arthrosi Therapeutics, Inc., a late-stage biotechnology company developing a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and Tophi in patients with gout, today announced the acceptance of two presentations, including one poster tour at the European League Against Rheumatism (EULAR) Congress 2024 meeting, being held in Vienna, Austria on June 12-15. Details for the poster presentations are as follows: Title: AR882, a Novel and Selective URAT1 Inhibitor, Significantly Reduced Tophi in Patients with Chronic Gouty Arthritis: Results of 12-month Outcome from a Global Trial using Digital Caliper Measurements and Dual Energy Computed Tomography Session Title: Clinical Poster Tours: Gout treatment in 2024 Presenting Author: Robert Keenan, M.D., Chief Medical Officer of Arthrosi Therapeutics Abstract Number: POS0268 Date/Time: Friday, June 14 / 9:30am-10:30am CEST Title: AR882, a Selective URAT1 Inhibitor, Exhibits No Drug-Drug Interactions with Key Renal, Hepatic, and GI Transporters Presenting Author: Litain Yeh, Ph.D, Co-Founder and Chief Executive Officer of Arthrosi Therapeutics Abstract Number: POS0935 Date/Time: Friday, June 14 / 9:30am-10:30am CEST About Gout: In the U.S., an estimated 13 million individuals are diagnosed with gout. Gout is a form of inflammatory arthritis that can significantly diminish mobility, functionality, and overall quality of life. Gout emerges from the crystallization of uric acid within the joints and soft tissue, instigating painful flare-ups and chronic symptoms. The kidneys play a pivotal role in the process, as they are responsible for filtering out and excreting uric acid from the body. In over 90% of gout patients, underexcretion of uric acid results in the imbalanced and elevated sUA levels that can lead to the deposition of uric acid crystals. It's essential to monitor and manage sUA levels as part of comprehensive gout treatment and prevention strategies. About Arthrosi: Arthrosi Therapeutics, Inc., headquartered in San Diego, CA, is focused on developing AR882, a potentially best-in-class, highly potent and selective next generation URAT1 inhibitor to reduce serum urate levels, flares and Tophi in patients with gout. Gout remains a large and growing market with ~ 13M patients in the U.S. alone, ~2M of which have tophaceous gout. AR882 has demonstrated encouraging efficacy and safety compared to SOC in Phase 2 studies as well as impressive results in achieving complete resolution of tophi in a Phase 2b study. Arthrosi anticipates initiating pivotal phase 3 program in early 2024. Investor Contact: Stern Investor Relations, Inc. Alex Lobo 212-698-8802 Alex.lobo@sternir.com View original content to download multimedia: SOURCE Arthrosi Therapeutics