PKD1

- New data on povetacicept 80 mg SC Q4 weeks in IgA nephropathy shows mean UPCR reduction from baseline of 66% observed at 48 weeks, associated with stable renal function (eGFR) and 63% achieving clinical remission -- - First proteinuria data on povetacicept in primary membranous nephropathy shows mean UPCR reduction from baseline of 62% at 24 weeks – - Global Phase 3 RAINIER trial of povetacicept in IgA nephropathy now underway – – Enrollment and dosing ongoing in Phase 3 portion of the global Phase 2/3 pivotal clinical trial of inaxaplin for the treatment of APOL1-mediated kidney disease – BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today provided updates on multiple kidney diseases in its pipeline including IgA nephropathy (IgAN), primary membranous nephropathy (pMN), and APOL1-mediated kidney disease (AMKD). These updates demonstrate the transformative potential of Vertex’s investigational therapies in multiple serious kidney diseases, and include positive new data on povetacicept, a dual inhibitor of the BAFF and APRIL pathways, in IgAN and pMN, presented at the American Society of Nephrology’s (ASN) Kidney Week Congress on October 23-27 in San Diego, California. “We are very pleased with the broadening of our innovative pipeline in renal medicine which now spans programs in AMKD, IgAN, pMN and polycystic kidney disease,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “The new data in IgAN and pMN we shared at this year’s ASN congress continue to reinforce povetacicept as a potential best-in-class therapy and demonstrate its potential as a pipeline-in-a-product. We also continue to make progress in AMKD and autosomal dominant polycystic kidney disease (ADPKD) where we are advancing the first potential treatments to address the underlying cause of these diseases.” Povetacicept in IgAN Vertex presented data on 54 patients with IgAN who received povetacicept 80 mg or 240 mg subcutaneously every 4 weeks (SC Q4W). Treatment with povetacicept 80 mg SC Q4W demonstrated a clinically meaningful decrease in proteinuria, with a mean 66% reduction from baseline in urine protein to creatinine ratio at 48 weeks (UPCR; n=8) associated with stable renal function over 48 weeks as assessed by estimated glomerular filtration rate (eGFR). By 48 weeks, 63% (5 out of 8) of study participants achieved clinical remission, defined as UPCR 50% reduction in UPCR from baseline. Anti-PLA2R1 autoantibodies, which are a marker of disease activity and associated with clinical outcomes, decreased from baseline by a mean of 87% at week 20. Povetacicept was well tolerated in patients with pMN, with AEs that were mild or moderate in severity. There were no SAEs related to povetacicept. A poster presentation #TH-PO589 entitled “Updated Results with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary Membranous Nephropathy (RUBY-3 Study)” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT. AMKD Vertex is developing inaxaplin, a potential first-in-class, investigational, oral small molecule inhibitor of APOL1, with the goal of targeting the underlying cause of AMKD. Enrollment and dosing are ongoing in the Phase 3 portion of the global Phase 2/3 pivotal AMPLITUDE clinical trial of inaxaplin. Vertex has the following AMKD poster presentations at ASN: Poster presentation #TH-P01203 entitled “AMPLITUDE: A Phase 2/3 Adaptive Trial of Inaxaplin in APOL1-mediated Kidney Disease” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT. Poster presentation #SA-PO701 entitled “Small Molecule APOL1 Channel Inhibitor Reduces Proteinuria, Rescues Podocyte Injury, and Reverses eGFR Decline in an APOL1-Mediated Kidney Disease Mouse Model” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT. Poster presentation #SA-PO700 entitled “Small Molecule Inhibition of APOL1 Channel Activity Protects Podocytes from Mitochondrial Dysfunction, Cell Death and Barrier Disruption Induced by APOL1 Risk Variants” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT. All accepted abstracts are available online on the ASN website . About IgA Nephropathy (IgAN) IgAN is a serious, progressive, life-threatening, B cell-mediated chronic kidney disease that is the most common cause of primary (idiopathic) glomerulonephritis, affecting people worldwide including approximately 130,000 people in the U.S. IgAN results from deposition of circulating immune complexes consisting of immunoglobulins and galactose-deficient immunoglobulin A (Gd-IgA1) in the renal glomerular mesangium, triggering kidney injury and fibrosis. A high percentage of people with IgAN progress to end-stage renal disease. There are no approved therapies that specifically target the underlying cause of IgAN. About RAINIER RAINIER is a global Phase 3 pivotal trial of povetacicept 80 mg vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating UPCR for the povetacicept arm versus placebo after a certain number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total eGFR slope through Week 104. About Primary Membranous Nephropathy (pMN) Primary membranous nephropathy is a serious, progressive, life-threatening B cell-mediated chronic kidney disease affecting people worldwide, with approximately 60,000 people diagnosed in the U.S. pMN causes a patient’s immune system to damage the glomeruli and may cause progressive loss of kidney function. There are no approved therapies that specifically target the underlying cause of pMN. About RUBY-3 RUBY-3 is an ongoing, multiple ascending dose, multi-cohort, open label, Phase 1/2 basket study of povetacicept in autoimmune glomerulonephritis, including IgAN, pMN, lupus nephritis and ANCA-associated vasculitis with glomerulonephritis where povetacicept is being administered subcutaneously for up to 104 weeks. About Povetacicept Povetacicept is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has higher binding affinity and greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and has demonstrated potential best-in-class efficacy in a clinical trial in patients with IgA nephropathy and primary membranous nephropathy. Povetacicept is also in development for multiple serious diseases including other autoimmune kidney diseases and autoimmune cytopenias. About APOL1-Mediated Kidney Disease (AMKD) AMKD is a genetic kidney disease affecting approximately 100,000 people in the U.S. and Europe. AMKD is caused by two variants of the APOL1 gene, which exert a toxic effect on kidney cells, leading to cell injury, cell death and damage to glomeruli (which filter blood to the kidney). Even after treatment with currently available therapies, people with AMKD often progress to kidney failure. Kidney failure is treated with frequent, long-term dialysis or a kidney transplant. Both require lifelong treatment and follow-up and carry a high mortality risk . There are currently no approved treatments that address the underlying cause of AMKD. About Inaxaplin Inaxaplin is a potential first-in-class, investigational small molecule inhibitor of APOL1, and the first investigational therapy aimed at treating the underlying cause of AMKD. About AMPLITUDE AMPLITUDE is a global Phase 2/3 pivotal trial of inaxaplin for the treatment of AMKD, in which a 45 mg once daily oral dose is compared to placebo, on top of standard of care. The study is designed to have a pre-planned interim analysis at Week 48 evaluating estimated glomerular filtration rate (eGFR) slope, a measure of kidney function, supported by a percent change from baseline in proteinuria, in the inaxaplin arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Enrollment and dosing are ongoing in the Phase 3 portion of the study. About Autosomal Dominant Polycystic Kidney Disease (ADPKD) ADPKD is the most common inherited kidney disease and one of the most common severe Mendelian genetic diseases, affecting approximately 250,000 diagnosed people in the U.S. and Europe. As an autosomal dominant disease, one affected parent can pass on the disease to their children. In most cases, ADPKD is caused by variants in the PKD1 and PKD2 genes, which express proteins known as polycystins. The majority of ADPKD patients (~80%) have a variant in the PKD1 gene, resulting in a loss of function of polycystin 1 (PC1). This leads to the proliferation of kidney epithelial cells, increased fluid secretion and the formation and expansion of numerous fluid-filled cysts. The progressive cyst formation causes an increase in kidney size and decline in kidney function. Around half of patients with ADPKD experience kidney failure by the age of 60. Kidney cysts can also lead to severe abdominal pain, cyst infection, blood in the urine and kidney stones, all of which significantly impair quality of life. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 15 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Vertex Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements by Carmen Bozic, M.D., in this press release, and statements regarding Vertex’s expectations and plans for the global Phase 3 RAINIER study of povetacicept, including the potential for an interim analysis to serve as the basis to seek accelerated approval in the U.S., and expectations and plans for the Phase 3 portion of the clinical trial of inaxaplin, including the potential for an interim analysis to serve as the basis to seek accelerated approval in the U.S. While we believe the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company’s beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company’s development programs may not support registration or further development of its compounds due to safety, efficacy, and other reasons, and other risks listed under the heading “Risk Factors” in Vertex’s most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company’s website at . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com Media: mediainfo@vrtx.com or International: +44 20 3204 5275 or U.S.: 617-341-6992 or Heather Nichols: +1 617-839-3607

SAN DIEGO, Oct. 8, 2024 /PRNewswire/ -- Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), today announced it has completed enrollment of 26 patients in the fourth cohort in the Phase 1b MAD study of RGLS8429 for the treatment of ADPKD. "The completion of enrollment of our final cohort marks an important milestone as we near the end of our Phase 1b study. We have been pleased to see positive results from each of the prior three cohorts, showing continued evidence of a mechanistic dose response based on increase in urinary polycystins (PC1 and PC2), across cohorts. Additionally, exploratory imaging analysis has shown mean reductions in height adjusted total kidney volume (htTKV), a key measurement which we will be evaluating in the fourth cohort and in the potentially pivotal Phase 3 trial," said Jay Hagan, CEO of Regulus. "We remain on track for an End of Phase 1 meeting with the FDA by the end of 2024, and we plan to share topline data from a substantial number of patients in cohort four in early 2025." The Phase 1b MAD study is a double-blind, placebo-controlled, weight-based dosing and an open-label fixed dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study is evaluating RGLS8429 treatment across three different weight-based dose levels (cohort 1-3) and one fixed dose level (cohort 4), including measuring changes in urinary polycystins PC1 and PC2, height adjusted total kidney volume (htTKV), cyst architecture, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and have been shown to inversely correlate with disease severity. Patients in the fourth cohort are receiving a fixed dose of 300 mg of RGLS8429 administered every other week for three months. More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191). About ADPKD Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 160,000 individuals are diagnosed with the disease in the United States alone, with an estimated global prevalence of 4 to 7 million. About RGLS8429 RGLS8429 is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of RGLS8429 has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study demonstrated that RGLS8429 has a favorable safety and PK profile. RGLS8429 was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study Regulus announced topline data from the first cohort of patients in September 2023, from the second cohort of patients in March 2024 and from the third cohort of patients in June 2024. Regulus completed enrollment in the fourth cohort of patients in October 2024. Patients in the fourth cohort are receiving a 300 mg fixed dose of RGLS8429 administered every other week for three months. About Regulus Regulus Therapeutics Inc. (Nasdaq: RGLS) is a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs. Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a pipeline complemented by a rich intellectual property estate in the microRNA field. Regulus maintains its corporate headquarters in San Diego, CA. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the Company's RGLS8429 program and preclinical pipeline, the potential that RGLS8429 may be eligible for an Accelerated Approval pathway, potentially achieving therapeutic efficacy and clinical translation for patients, the expected timing for reporting interim or topline data, and the timing and future occurrence of other preclinical and clinical activities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risk that the approach we are taking to discover and develop drugs is novel and may never lead to marketable products, that preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and may not be indicative of future results, the FDA has not designated RGLS8429 for an Accelerated Approval pathway and such designation may not lead to a faster development, regulatory review or approval process and does not increase the likelihood that RGLS8429 will receive marketing approval, the risk that preclinical and clinical studies may not be successful, risks related to regulatory review and approval, risks related to our reliance on third-party collaborators and other third parties, risks related to intellectual property, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, the risk that additional toxicology data may be negative, and risks related to our ability to successfully secure and deploy capital. These and other risks are described in additional detail in Regulus' filings with the Securities and Exchange Commission, including under the "Risk Factors" heading of Regulus' quarterly report on Form 10-Q available on the Company's website or at . All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. SOURCE Regulus Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

● 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.