XORTX Highlights Pioneering Research Indicating a Role for Genetic Regulation of Xanthine Oxidase and Therapeutic Targeting of Aberrant Purine Metabolism
XORTX Therapeutics Inc. (NASDAQ: XRTX) highlights recent research indicating genetic factors are linked to over-expression of xanthine oxidase (XO), supporting the company's approach to treating kidney diseases. The research suggests XO modulates progression of chronic kidney disease, diabetic kidney disease, and polycystic kidney disease. CEO Allen Davidoff emphasized the potential of pharmacologic targeting of XO, especially where increased XO activity is associated with kidney diseases.
The company's proprietary formulation, XORLO™, will be tested in a planned clinical trial for patients with autosomal dominant polycystic kidney disease (ADPKD). This trial aims to further understand the role of newly identified genetic factors in individuals with PKD. XORTX believes its expertise in developing XO inhibitors, protected by patents, positions the company to deliver targeted therapeutics to at-risk individuals.
XORTX Therapeutics Inc. (NASDAQ: XRTX) mette in evidenza recenti ricerche che indicano come fattori genetici siano legati all'over-espressione della xantina ossidasi (XO), supportando l'approccio dell'azienda nel trattamento delle malattie renali. La ricerca suggerisce che XO modula la progressione della malattia renale cronica, della malattia renale diabetica e della malattia renale policistica. Il CEO Allen Davidoff ha sottolineato il potenziale del targeting farmacologico di XO, specialmente dove un'attività aumentata di XO è associata a malattie renali.
La formulazione proprietaria dell'azienda, XORLO™, sarà testata in un trial clinico programmato per pazienti con malattia renale policistica autosomica dominante (ADPKD). Questo trial mira a comprendere meglio il ruolo dei fattori genetici recentemente identificati negli individui con PKD. XORTX crede che la sua esperienza nello sviluppo di inibitori di XO, protetti da brevetti, posizioni l'azienda per fornire terapie mirate agli individui a rischio.
XORTX Therapeutics Inc. (NASDAQ: XRTX) destaca investigaciones recientes que indican que los factores genéticos están relacionados con la sobreexpresión de la xantina oxidasa (XO), apoyando el enfoque de la empresa para tratar enfermedades renales. La investigación sugiere que XO modula la progresión de la enfermedad renal crónica, la enfermedad renal diabética y la enfermedad renal poliquística. El CEO Allen Davidoff enfatizó el potencial del tratamiento farmacológico dirigido a XO, especialmente donde la actividad aumentada de XO está asociada con enfermedades renales.
La formulación patentada de la empresa, XORLO™, será probada en un ensayo clínico planificado para pacientes con enfermedad renal poliquística autosómica dominante (ADPKD). Este ensayo tiene como objetivo comprender mejor el papel de los factores genéticos recién identificados en individuos con PKD. XORTX cree que su experiencia en el desarrollo de inhibidores de XO, protegidos por patentes, posiciona a la empresa para proporcionar terapias dirigidas a individuos en riesgo.
XORTX Therapeutics Inc. (NASDAQ: XRTX)는 최근 연구 결과가 유전적 요인이 잔틴 산화효소 (XO)의 과발현과 관련이 있음을 강조하며, 이를 통해 회사의 신장 질환 치료 접근 방식을 뒷받침한다고 밝혔습니다. 연구 결과에 따르면, XO는 만성 신장 질환, 당뇨병성 신장 질환 및 다낭성 신장 질환의 진행을 조절한다고 합니다. CEO 앨런 다비도프는 특히 신장 질환과 관련된 XO 활성이 증가하는 경우, XO를 약리적으로 표적 하는 것이 잠재력이 있음을 강조했습니다.
회사의 독점 제형인 XORLO™는 자가 우성 다낭성 신장 질환 (ADPKD) 환자를 대상으로 예정된 임상 시험에서 테스트될 예정입니다. 이 시험은 PKD 환자의 유전자 요인의 역할을 더욱 이해하는 것을 목표로 하고 있습니다. XORTX는 XO 억제제 개발에 대한 전문성이 특허로 보호되어 있으며, 이를 통해 위험에 처한 개인에게 표적 치료제를 제공할 수 있는 위치에 있다고 믿고 있습니다.
XORTX Therapeutics Inc. (NASDAQ: XRTX) souligne des recherches récentes indiquant que des facteurs génétiques sont liés à une surexpression de la xanthine oxidase (XO), soutenant ainsi l'approche de l'entreprise pour traiter les maladies rénales. La recherche suggère que XO module la progression de la maladie rénale chronique, de la maladie rénale diabétique et de la maladie rénale polykystique. Le PDG Allen Davidoff a souligné le potentiel du ciblage pharmacologique de XO, notamment dans les cas où une activité XO accrue est associée à des maladies rénales.
La formulation propriétaire de l'entreprise, XORLO™, sera testée dans un essai clinique prévu pour des patients atteints de maladie rénale polykystique autosomique dominante (ADPKD). Cet essai vise à mieux comprendre le rôle des facteurs génétiques nouvellement identifiés chez les individus atteints de PKD. XORTX estime que son expertise dans le développement d'inhibiteurs de XO, protégée par des brevets, positionne l'entreprise pour fournir des thérapies ciblées aux personnes à risque.
XORTX Therapeutics Inc. (NASDAQ: XRTX) hebt aktuelle Forschungen hervor, die zeigen, dass genetische Faktoren mit einer Überexpression der Xanthinoxidase (XO) verbunden sind. Dies unterstützt den Ansatz des Unternehmens zur Behandlung von Nierenerkrankungen. Die Forschung legt nahe, dass XO den Verlauf von chronischen Nierenerkrankungen, diabetischen Nierenerkrankungen und polyzystischen Nierenerkrankungen moduliert. CEO Allen Davidoff betonte das Potenzial der pharmakologischen Zielsetzung von XO, insbesondere dort, wo eine erhöhte XO-Aktivität mit Nierenerkrankungen assoziiert ist.
Die firmeneigene Formulierung, XORLO™, wird in einer geplanten klinischen Studie bei Patienten mit autosomal-dominanter polyzystischer Nierenerkrankung (ADPKD) getestet. Diese Studie zielt darauf ab, die Rolle neu identifizierter genetischer Faktoren bei Personen mit PKD besser zu verstehen. XORTX ist der Ansicht, dass ihr Fachwissen in der Entwicklung von XO-Hemmern, die durch Patente geschützt sind, das Unternehmen in die Lage versetzt, gezielte Therapeutika für gefährdete Personen bereitzustellen.
- Research supports XORTX's approach to treating kidney diseases by inhibiting xanthine oxidase (XO)
- Planned clinical trial for XORLO™ in ADPKD patients
- Patent portfolio protecting XO inhibitor development
- Potential for personalized therapeutic approach based on genetic factors
- Evidence for over-expression of XO in human PKD not yet reported
Insights
This research highlights the potential of xanthine oxidase (XO) inhibition as a therapeutic strategy for various kidney diseases. The genetic link to XO over-expression in conditions like polycystic kidney disease (PKD), diabetic kidney disease and chronic kidney disease is particularly intriguing. It suggests a precision medicine approach could be valuable, targeting patients with specific genetic variants.
The company's focus on developing XO inhibitors, particularly XORLO™ (oxypurinol), aligns well with these findings. The planned clinical trial in ADPKD patients could provide important data on the efficacy of this approach and potentially validate the genetic factors involved. However, it's important to note that while animal models show promise, human evidence for XO over-expression in PKD is still lacking. This gap in knowledge adds an element of risk to the company's strategy.
XORTX's strategic positioning in the XO inhibitor space could be a significant advantage if these genetic links are further validated. The company's existing patent portfolio, which anticipated this opportunity, may provide a competitive edge in developing targeted therapeutics. However, investors should be aware that the path from preclinical research to approved drugs is long and uncertain.
The potential for a precision medicine approach could expand XORTX's market opportunities beyond just ADPKD to other kidney diseases and possibly conditions like sepsis and diabetes. This broadens the company's potential revenue streams. However, the lack of current human evidence for XO over-expression in PKD is a risk factor that could impact the success of their lead program. Investors should closely monitor the outcomes of the planned ADPKD clinical trial as a key indicator of the company's future prospects.
● 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 2024
- Major TJ, et all, Evaluation of the diet wide contribution to serum urate levels: Met-analysis of population based cohorts, BMJ, 363, k3952, 2018
- Gao, Li et al., Xanthine oxidoreductase gene polymorphism are associated with high risk of sepsis and organ failure, Respir. Res, 24, 177_2023
- Liu H, et al., Genetic variants in XDH are associated with prognosis off gastric cancer in a Chines population, 663, 196, 2013
- Wang 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, 2010
- Boban 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, CEO adavidoff@xortx.com or +1 403 455 7727 Kim Golodetz, LHA Investor Relations kgolodetz@lhai.com or +1 212 838 3777 | Nick Rigopulos, Director of Communications nick@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.
FAQ
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