XO

● Xanthine oxidase reported to modulate progression of chronic kidney disease, diabetic kidney disease, polycystic kidney disease, and other indications ● CALGARY, Alberta, Aug. 29, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANU), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to report that recent peer-reviewed, independent, published research highlights that genetic factors are linked to the over-expression of xanthine oxidase (“XO”) and play a role in several diseases, including kidney disease. These ground-breaking findings further support the Company’s approach to treating kidney and other diseases by inhibiting XO. Xanthine oxidase is an essential enzyme within the uric acid metabolic pathway and is required for the breakdown of purine nucleotides. The breakdown products of XO, including uric acid (“UA”) and reactive oxygen species (“ROS”), are released during the enzymatic reaction and may play a detrimental role in the circulatory system and within tissue during disease. XORTX sponsored discoveries in rodent models of polycystic kidney disease (“PKD”) implicate over-expression or over-activity of XO as a potentially important target in treating this disease. Evidence for over-expression of XO in human PKD has not been reported to date, although work by Wang et al. suggests linkage of genetic factors to PKD1. Recently, new emerging discoveries link genetic factors to specific populations and show that higher XO expression is associated with a variety of conditions including hyperuricemia2, sepsis, organ failure and sepsis associated acute respiratory distress syndrome (ARDS)3,4, kidney dysfunction3,4, diabetes5, PKD1,5 and kidney failure6,7. From a mechanistic standpoint, these studies advocate for a precision-medicine approach in which genetic risk variants would guide treatment decisions1. Commenting on the research, Allen Davidoff, Ph.D., CEO of XORTX, stated, “The combination of pioneering research in autosomal dominant polycystic kidney disease (“ADPKD”) sponsored by XORTX and these peer-reviewed, published research papers support our belief that pharmacologic targeting of XO holds enormous therapeutic potential, specifically where increased XO activity is associated with non-diabetic or diabetic kidney diseases. These discoveries highlight an opportunity to develop a personalized therapeutic approach for individuals whose unique genetic factors predisposed them to disease, and the need for xanthine oxidase inhibition to treat those individuals at risk. We believe that XORTX’s expertise in developing XO inhibitors, protected by a patent portfolio that anticipated this opportunity, combined with our therapeutic platform is ideally positioned to deliver targeted therapeutics to individuals. Our planned clinical trial in patients with ADPKD will test XORLO™, our proprietary formulation of oxypurinol, and will also provide an opportunity to further understand the role of these newly identified genetic factors in individuals with PKD.” References: Korsmo HW, Emerging roles of xanthine oxidoreductase in chronic kidney disease, Antioxidants, June 2024Major TJ, et all, Evaluation of the diet wide contribution to serum urate levels: Met-analysis of population based cohorts, BMJ, 363, k3952, 2018Gao, Li et al., Xanthine oxidoreductase gene polymorphism are associated with high risk of sepsis and organ failure, Respir. Res, 24, 177_2023Liu H, et al., Genetic variants in XDH are associated with prognosis off gastric cancer in a Chines population, 663, 196, 2013Wang et al., Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR, ” The authors identified an expression quantitative trait loci (QTL) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (XO), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in diabetic kidney disease in male mice. They concluded that certain types of alleles of a gene that controls the expression of xanthine oxidase can be over expressed in CKD, diabetic kidney disease and polycystic kidney disease.Kudo M et al., Functional Characterization of Genetic Polymorphisms Identified In the Promotor Region of the Xanthine Oxidase Gene, Drug Metab. Pharmacokinet., 25, 599, 2010Boban M, et al., Circulating purine compound, uric acid, and xanthine oxidase/dehydrogenate relationship in essential hypertension and end stage renal disease., Ren. Fail., 36, 613, 2014 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, CEOadavidoff@xortx.com or +1 403 455 7727Kim Golodetz, LHA Investor Relationskgolodetz@lhai.com or +1 212 838 3777Nick Rigopulos, Director of Communicationsnick@alpineequityadv.com or +1 617 901 0785 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.

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.

CALGARY, Alberta, April 22, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANUA WKN: A3UNZ), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to announce a research paper titled “Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models" has been accepted for publication in the peer-reviewed American Journal of Physiology-Renal Physiology and published online April 19, 2024. This study reports health consequences associated with increasing serum uric acid (“SUA”) in mice or rat models of Autosomal Dominant Polycystic Kidney Disease (“ADPKD”), specifically the effects of increasing SUA on cyst growth and kidney size. Cyst genesis and cyst growth (together “cyst index”) and their rates of change are important indicators of disease progression and are correlated with declining filtering capacity and end stage renal disease (“ESRD”). This study shows, for the first time, that chronically increased SUA can significantly increase cyst index and increase kidney size in ADPKD. According to the study’s findings, saturating concentrations of SUA contributing to “crystal injury” were not necessary to negatively alter both structure and function of the ADPKD kidney. Moderately high SUA concentrations were also found to be associated with an increased inflammatory state (cytokine profile) in both serum and kidney tissue. Independent of the modifying effects of chronically increased SUA, a fundamental new discovery from this study was that over expression of xanthine oxidase (“XO”) in kidney tissue was present, suggesting aberrant purine metabolism may be present in ADPKD and suggesting a possible role of XO in disease progression. When considered together, SUA above the normal range and overexpression of XO, especially in the location of cysts, in an ADPKD kidney represents a strong impetus for the use of XO inhibition to attenuate this newly described mechanism of injury. Inhibition of XO using XORLO™, XORTX’s proprietary formulation of oxypurinol, substantially lowered uric acid concentrations, attenuated the effects of chronically increased SUA on cyst index and kidney size in the RC/RC mouse model of ADPKD in this study. Dr. Allen Davidoff, CEO of XORTX, stated, “We are pleased to have supported this pioneering research in polycystic kidney disease by Dr. Charles Edelstein of the University of Colorado. Identifying for the first time that increased serum uric acid and possibly overexpression of xanthine oxidase in the ADPKD kidney can accelerate disease progression has substantial implications. This study provides important novel insight into one modifying factor that has the potential to accelerate ADPKD progression. In human ADPKD, kidney size and declining kidney filtering capacity are correlated and are key indicators of disease progression and prognosis. Identifying any modifiable factor that explains variable outcomes in individuals with ADPKD is a seminal step forward in our understanding of this disease. XORLOTM was shown to attenuate this effect. In concept, XORLOTM should be capable of attenuating both of these modifiable factors. These mechanistic studies are important for the planning of future clinical studies of xanthine oxidase inhibition in patients with ADPKD.” 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 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, 2019 Bergmann 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, 2018 Gimpel C., Bermann 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, 2019 Communications and Social Media Engagements Further to the Company’s press release of April 8, 2024, XORTX continues its participation in important healthcare and investor conferences, including most recently the Noble Capital Markets Emerging Growth Virtual Healthcare Equity Conference and the CEM Scottsdale Capital Event. Additional information on how to listen to webcast presentations, where available, will be provided at a later date. The Company is also augmenting investor awareness through the engagement of marketing and communication consultants, including: LFG Equities has been engaged to provide marketing consulting and market communications services, for a fee of US$50,000 for a one-month period. The LFG Equities engagement can be extended by mutual consent and can be terminated by XORTX upon 10 days’ notice. IRPUB has been engaged to provide a XORTX awareness campaign for a fee of US$40,000 for a term of four months. The IRPUB engagement can be extended by mutual consent and can be terminated by XORTX at that time. FeMax Publishing and Consulting Ltd. has been engaged to analyze and assess European communications and investor contact outreach in Europe. The term of the contract is for 12 months with the assessment services at a monthly fee of €3,500 and the European Awareness campaign at a monthly fee of €8,500. The FeMax Publishing and Consulting engagement can be extended by mutual consent. About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with two clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD is in preparation to conduct a single registration trial – XRX-OXY-201, that is eligible for accelerated approval; 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 . For more information, please contact: Allen Davidoff, CEO Nick Rigopulos, Director of Communications adavidoff@xortx.com or +1 403 455 7727 nick@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 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. 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, (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 .