Diabetic Nephropathies

Vivoryon Therapeutics N.V. Presents Outstanding Phase 2b Results of Varoglutamstat on Kidney Function at ASN Kidney Week 2024 Selected for late-breaking oral presentation at ASN kidney week, the world’s premier nephrology meetingResults presented show a statistically significant and clinically meaningful improvement of the prospectively defined kidney function parameter eGFR1 by 3.4mL/min/year (p<0.0001) in the varoglutamstat arm compared to placebo Results in the subgroup of patients with diabetes2 showed an 8.2mL/min/year difference in favor of varoglutamstat (p=0.02)The results were consistent in several sensitivity analyses including using the CKD-EPI 2021 formula for both creatinine and cystatin-CVaroglutamstat demonstrated an excellent safety and tolerability profile and there were no signs of increased proteinuriaA new Phase 2 study is in planning to confirm the effect in patients with DKD3 stage 3b and 4 Halle (Saale) / Munich, Germany, October 26, 2024 – Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, today announced highlights from a late-breaking oral presentation held yesterday, October 25, 2024, at the American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California. The presentation by the Company’s CEO, Frank Weber, M.D. titled “Varoglutamstat Increases Glomerular Filtration in Elderly Patients without Signs of Proteinuria and Potentially Offers a New Approach to Treat Diabetic Kidney Disease (DKD)” featured Phase 2 clinical study data substantiating the opportunity to further develop varoglutamstat, Vivoryon’s Phase 2 investigational medicine with the potential to improve kidney function, in people with kidney disease. “We’re privileged to have been accepted to share the exciting results of varoglutamstat on kidney function with so many scientific and medical experts in the kidney field. Varoglutamstat showed statistically significant and clinically meaningful improvements of eGFR versus placebo and a sustained improvement of eGFR above baseline, potentially indicating partial recovery of the kidney. We are grateful for many fruitful discussions and extremely encouraged by the positive reactions we received from the community,” said Frank Weber, M.D., CEO of Vivoryon. “The efficacy and safety data presented at ASN represent a unique profile for an oral product for treating kidney disorders and guide the future development of varoglutamstat. Our primary focus is delivering a much-needed novel treatment option for patients suffering from DKD. Beyond this, we see potential for varoglutamstat across a broad range of kidney diseases including rare diseases affecting kidney function, such as Fabry disease and Alport syndrome.” Presentation Highlights Background: Varoglutamstat is a specific and selective inhibitor of glutaminyl cyclases and confers a novel mechanism of action that attenuates inflammation and fibrosis through reduction of pyroglutamized versions of chemokines and pro-fibrotic peptides, thereby positively impacting kidney function.Assessment of progression of kidney dysfunction as measured by the eGFR slope4 was included prospectively in VIVIAD (NCT04498650), Vivoryon’s Phase 2b multicenter, randomized, double-blind, placebo-controlled, parallel group dose-finding study in 259 patients in Alzheimer’s disease.The average age of participants in VIVIAD was >68 years, dosing was twice-daily with either 300mg or 600mg varoglutamstat, or placebo and treatment duration was 48-96 weeks; key kidney-related study features included a mean baseline eGFR of ~80mL/min/1.73m2, eGFR, urine dipstick and vital signs measured every 12 weeks; the diabetes subgroup comprised ~12% of VIVIAD patients. Compelling efficacy and safety data in elderly people at risk for kidney disease: eGFR improved significantly for varoglutamstat compared to placebo and above baseline in both total population and diabetes subgroup, with the latter revealing a substantially higher treatment effect5 of >8.2mL/min/1.73m2/year (p=0.02; varoglutamstat n=20 / placebo n=12) compared to the overall VIVIAD study population (3.4mL/min/1.73m2/year (p<0.001; varoglutamstat n=141 / placebo n=117)).Results and effect size were consistent using a set of diverse and validated methods for eGFR assessment (2021 CKD-EPI cystatin C, 2021 CKD-EPI creatinine-cystatin C 2021 CKD-EPI creatinine, MDRD6).Urine dipstick analysis showed no evidence of increased proteinuria in the treatment group compared to placebo, with the majority of study participants having no proteinuria through all time points measured in the study.Robust safety data confirmed varoglutamstat’s excellent safety profile consistent across two years study duration with no adverse kidney effects and no meaningful differences observed in renal and metabolic systems adverse events in both total population and diabetes subgroup. Next steps: Placebo-controlled Phase 2 study in stage 3b/4 DKD patients on top of SoC in planning to confirm the results to date and investigate additional endpoints including albuminuria/proteinuria, inflammation and fibrosis-related biomarkers.Pre-clinical investigation of additional rare/orphan kidney disorders (Alport syndrome, Fabry disease). 1 Estimated glomerular filtration rate (eGFR), a validated measure of kidney function, was calculated as a slope analysis across two years taking all available data into account. 2 Diabetes subgroup defined as patients having at baseline either medical history of diabetes (type 1 or 2) and/or comedication with drugs used in diabetes and/or untreated with an HbA1c > 6.5%. 3 The timing and execution of the planned Phase 2 study in diabetic kidney disease is subject to additional funding / partnership. 4 Measuring the eGFR slope via random coefficients (RC) analysis was the primary efficacy endpoint in recent FDA approvals in CKD, as well as in many ongoing Phase 3 studies. 5 Treatment effect – the between-group difference in eGFR slope between varoglutamstat and placebo. 6 Estimated glomerular filtration rate based on creatinine and calculated using modification of diet in renal disease (MDRD) method. ### Varoglutamstat in Kidney DiseaseVaroglutamstat (PQ912) is a proprietary, potent and selective inhibitor of human glutaminyl cyclases QPCT and QPCTL with therapeutic potential in indications including inflammatory and fibrotic diseases, neurodegenerative diseases, cancer and others. Initially advancing development aiming to treat Alzheimer’s disease (AD), varoglutamstat has been investigated in a number of different clinical studies, all of which have consistently demonstrated a favorable safety and tolerability profile both in healthy volunteers and patients with AD. Based on the known anti-inflammatory activity of varoglutamstat, the protocol for the Phase 2 VIVIAD study in AD, which was completed in the first half of 2024, included the investigation of kidney function and measurement of biomarkers of kidney inflammation and fibrosis to explore the role of QPCT/L inhibition on kidney function. Although patients in VIVIAD were selected for their AD status and not for their kidney function level, many of them had reduced kidney function due to age and/or comorbidities. Analysis showed a statistically significant benefit of varoglutamstat on a prospectively defined key kidney function endpoint (eGFR) and a significant reduction of the pro-inflammatory cytokine pE-CCL2. A substantially higher treatment benefit of varoglutamstat on eGFR was observed in a post-hoc diabetes subgroup, triggering plans to advance varoglutamstat into Phase 2 study in DKD, which is currently in planning. About Vivoryon Therapeutics N.V.Vivoryon is a clinical stage biotechnology company focused on developing innovative small molecule-based medicines. Driven by its passion for ground-breaking science and innovation, the Company strives to change the lives of patients in need suffering from severe diseases. The Company leverages its in-depth expertise in understanding post-translational modifications to develop medicines that modulate the activity and stability of proteins which are altered in disease settings. The Company has established a pipeline of orally available small molecule inhibitors for various indications including Alzheimer’s disease, inflammatory and fibrotic disorders, including of the kidney, and cancer. www.vivoryon.com. Vivoryon Forward Looking StatementsThis press release includes forward-looking statements, including, without limitation, those regarding the business strategy, management plans and objectives for future operations of Vivoryon Therapeutics N.V. (the “Company”), estimates and projections with respect to the market for the Company’s products and forecasts and statements as to when the Company’s products may be available. Words such as “anticipate,” “believe,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “project,” “predict,” “should” and “will” and similar expressions as they relate to the Company are intended to identify such forward-looking statements. These forward-looking statements are not guarantees of future performance; rather they are based on the Management’s current expectations and assumptions about future events and trends, the economy and other future conditions. The forward-looking statements involve a number of known and unknown risks and uncertainties. These risks and uncertainties and other factors could materially adversely affect the outcome and financial effects of the plans and events described herein. The Company’s results of operations, cash needs, financial condition, liquidity, prospects, future transactions, strategies or events may differ materially from those expressed or implied in such forward-looking statements and from expectations. As a result, no undue reliance should be placed on such forward-looking statements. This press release does not contain risk factors. Certain risk factors that may affect the Company’s future financial results are discussed in the published annual financial statements of the Company. This press release, including any forward-looking statements, speaks only as of the date of this press release. The Company does not assume any obligation to update any information or forward-looking statements contained herein, save for any information required to be disclosed by law. For more information, please contact: Investor ContactVivoryon Therapeutics N.V.Dr. Manuela Bader, Director IR & CommunicationEmail: IR@vivoryon.com Media ContactTrophic CommunicationsValeria Fisher or Verena SchossmannTel: +49 175 8041816 / +49 151 219 412 77Email: vivoryon@trophic.eu Attachment 20241026_Vivoryon_ASN_KidneyWeek_Data

● Health consequences of chronically high uric acid and xanthine oxidase in polycystic kidney disease in rats, mice and humans ● CALGARY, Alberta, Oct. 24, 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 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. Selected results from the study include: In both Rat or Mouse models of Polycystic Kidney Disease (“PKD”) i) Use of a uricase inhibitor to increase uric acid resulted in increased cyst growthii) Xanthine oxidase (“XO”) inhibitor – Oxypurinol – decreased serum uric acid and cyst growthiii) Increased XO staining in kidney and liver was abundant Prospective / Retrospective Clinical Results of the Halt Clinical Trial - Group A - Early PKD patients iv) Patients with increased serum uric acid had increased total kidney volumev) Patients with increased serum uric acid had faster PKD progressionvi) Increase serum XO activity was associated with an earlier onset of high blood pressure About this Study The 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 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 rat, mice and human studies of PKD. The purpose of the study was to gain and 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. Dr. Allen Davidoff, CEO of XORTX commented, “Exploring and understanding the contribution of chronically increased serum uric acid and/or the effect of too much or too active XO enzyme in the circulation or tissue on PKD disease progression was a goal of this study. The study results presented today are another pioneering first step towards characterizing how and when to treat individuals with PKD as well as how they might benefit from the Company’s XRx-008 program, and our upcoming registration clinical trial. This study was a preliminary investigation of individuals with early stage PKD, and provided information regarding the health consequences of hyperuricemia and XO. The Company will continue to add to this exciting discovery with future exploration of later stage PKD, assessment of genetic factors contributing to aberrant purine metabolism, including XO overexpression, and this precision medicine opportunity.” 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 health of kidney disease 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 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.

Post hoc analysis evaluated sotagliflozin in patients with diabetic kidney disease (DKD) THE WOODLANDS, Texas, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced a new analysis of its Phase 3 SCORED clinical trial demonstrating the protective effects of sotagliflozin in patients with diabetic kidney disease (DKD). Data will be presented at Kidney Week 2024, the annual meeting of the American Society of Nephrology in San Diego, California. Previous analyses of the SCORED trial have shown that sotagliflozin, a dual SGLT1 & 2 inhibitor, reduced the risk of kidney and cardiorenal composite endpoints in patients with type 2 diabetes (T2D) and diabetic kidney disease (DKD). The objective of this new post hoc analysis of SCORED was to evaluate the effect of sotagliflozin versus placebo on Estimated Glomerular Filtration Rate (eGFR) slope, and the impact of baseline kidney function and glycemia. The eGFR slope assessment is widely used as a surrogate endpoint in cardiovascular and chronic kidney disease trials. Details for the presentation are as follows: “ Effect of sotagliflozin on eGFR slope by baseline kidney function and glycemic control ” – a moderated poster presentation, Friday, October 25, 10:00a.m.PT, 4:00-5:00p.m, Exhibit Hall, San Diego Convention Center, presented by Vikas S. Sridhar, M.D., University of Toronto, Ontario Within the entire cohort of 10,574 participants, a placebo-adjusted acute decline in eGFR of -2.59 ml/min/1.73m2/year (95% CI -2.88, -2.30; p<0.0001) was observed. The total placebo-adjusted slope was -0.08 ml/min/1.73m2/year (95% CI -0.43, 0.27; p=0.67). Compared to placebo, sotagliflozin had a greater benefit on chronic slope with increasing baseline albuminuria (P-interaction=0.023). Full study results will be discussed during the moderated poster and can be accessed here on the Kidney Week website. “Researchers observed positive renal protection with sotagliflozin across a spectrum of baseline kidney function and glycemic control. This study makes an important contribution to understanding the clinical benefits of sotagliflozin for people with diabetic kidney disease,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. About sotagliflozin Discovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. For Investor and Media Inquiries : Lisa DeFrancesco Lexicon Pharmaceuticals, Inc. lexinvest@lexpharma.com