Rasburicase

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 .

药渡数据-「全球临床月报」真实/可溯源/紧贴业内需求 01本月重磅药物临床数据公布 02本月重磅临床试验进展情况 03本月重要药物临床批准动态01重磅药物临床数据公布据药渡数据不完全统计，本月全球公布临床数据102个，其中III期临床公布数据18个，II期临床36个，I/II期临床22个，I期临床25个；治疗领域以血液和淋巴系统，肿瘤为主。福泽雷塞（IBI351）福泽雷塞是一款特异性共价不可逆的KRAS G12C抑制剂，可有效抑制该蛋白介导的GTP/GDP交换从而下调KRAS蛋白活化水平；临床前半胱氨酸选择性测试，也显示了福泽雷塞对于该突变位点的高选择性抑制效力。2023年11月24日，信达生物/劲方医药合作开发的KRAS G12C抑制剂福泽雷塞的上市申请获CDE受理并纳入优先审评程序，用于至少接受过一种系统性治疗的KRAS G12C突变的晚期非小细胞肺癌患者。GFH925X1101是一项在中国开展的临床II期单臂注册研究（NCT05005234），研究旨在评估IBI351单药在标准治疗失败或不耐受且携带KRAS G12C突变的晚期非小细胞肺癌受试者中的安全性、耐受性和疗效。截至2023年6月12日，该项研究共招募116位KRAS G12C突变的非小细胞肺癌患者，其中，接受过≥2线治疗的患者比例为41.4%，出现脑转移的患者比例为30.2%。初步临床数据展示出了优异的疗效和良好的安全性。目前全球共有2款KRAS G12C靶向药批准上市，中国尚未无相关创新药获批。2023年12月29日益方生物/正大天晴的Garsorasib上市申请获CDE受理，用于既往经一线系统治疗后疾病进展或不可耐受的KRAS G12C突变的局部晚期或转移性非小细胞肺癌患者。全球临床数据公布详情（部分）02重磅临床试验进展情况据药渡数据不完全统计，本月60个全球临床进展中，其中首例患者给药35个，涉及患者入组14项；治疗领域以神经系统，肿瘤，心血管系统及感染为主。RZ358目前先天性高胰岛素血症最常用的药物有二氮嗪和生长抑素类似物，尚未获得FDA批准用于所有形式疾病，并伴有难以忍受的副作用。RZ358是一种人源化单克隆抗体，作用于胰岛β细胞下游，有望广泛有效地治疗任何潜在遗传缺陷引起的先天性高胰岛素血症。2022年3月，Rezolute宣布IIb期临床试验取得积极结果，RZ358显著改善了先天性高胰岛素血糖患者的低血糖伴有良好的安全性和耐受性。2023年12月14日，Rezolute宣布开展RZ358的III期sunRIZE试验。这是一项多中心、随机、双盲、安慰剂对照的III期试验，旨在评估RZ358在低血糖控制不佳的先天性高胰岛素血症的疗效和安全性。招募人数：56人。48名1岁以上的参与者将被随机（2:1）接受RZ358 5mg/kg (16人）或16mg/kg（16人）或安慰剂（16人）。其余8名3个月到1岁的参与者将进行额外的开放标签试验，起始剂量5mg/kg，可根据需要增加至10mg/kg。主要疗效终点：24周平均每周低血糖事件的变化。关键次要终点：低血糖平均每日百分比时间的变化。全球临床进展详情（部分）03重要药物临床批准动态据药渡数据不完全统计2023年12月全球临床批准共计19个，主要治疗领域包括肿瘤，遗传代谢及感染。HP501HP501是海创药业自主研发的小分子化学创新药，是尿酸盐阴离子转运体1（Urate Anion Transporter 1，URAT1）的抑制剂，通过抑制URAT1的活性，减少尿酸盐的重吸收，从而促进尿酸排泄，降低血尿酸水平；黄嘌呤氧化酶抑制剂（Xanthine Oxidase Inhibitor，XOI），通过抑制黄嘌呤氧化酶（Xanthine Oxidase，XO）的活性来减少次黄嘌呤和黄嘌呤向尿酸转化，以减少体内尿酸的生成；HP501与黄嘌呤氧化酶抑制剂的联用是两种不同作用机制的药物联用， 对控制血尿酸能起到协同作用，增加降低血尿酸疗效。根据海创药业招股书显示，HP501在制剂上采取了缓释片剂，可在体内持续释放，一方面降低药物峰浓度，一方面能维持有效血药浓度。用药频率每天一次，提高患者依从性。海创药业正在开发HP501单药及联合XO抑制剂在高尿酸血症/痛风以及慢性肾病的临床研究。HP501已在国内完成了II期临床试验，初步结果表面，HP501比上市药物有效性更佳，且未发现肝肾副作用，目前正在启动III期注册性临床试验。目前高尿酸血症/痛风已成为我国仅次于糖尿病的第二大代谢类疾病。目前中国没有自主创新的痛风靶向药上市，随着日渐增长的临床需求，高尿酸血症/痛风的成为了国内研发热点，市场竞争越发激烈。全球临床批准详情（部分）咨询、合作请联系作者小D有话说为方便读者阅读及保存，我们将周报原文整理成了PDF版本，如需获取全文，可点击最上方蓝字，在药渡Daily公众号后台回复“12月临床月报”，即可下载。