Acute-On-Chronic Liver Failure

– Five presentations highlight TERLIVAZ research in adults with HRS with rapid reduction in kidney function,1 also known as HRS-AKI2 – DUBLIN, April 23, 2025 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, today announced the presentation of four posters and one oral presentation on TERLIVAZ® (terlipressin) for injection in patients with hepatorenal syndrome (HRS) with rapid reduction in kidney function,1 also known as HRS-acute kidney injury (AKI),2 at Digestive Disease Week (DDW), taking place in San Diego, CA from May 3-6, 2025. TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,1 also known as HRS-AKI,2 an acute and life-threatening condition requiring hospitalization.3 HRS-AKI is estimated to affect more than 42,000 Americans annually, approximately 0.01% of the U.S. population,4 making it a very rare condition; and rates of HRS hospitalizations are increasing.5 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. "We'll be sharing the results of five clinical data analyses at DDW, as we continue to evaluate TERLIVAZ's impact in real-world situations," said Peter Richardson, MRCP (UK), Executive Vice President & Chief Scientific Officer. "We look forward to connecting with digestive disease colleagues in San Diego and discussing treatment options like TERLIVAZ for appropriate patients." Abstract #4243460: Treatment and Outcomes of Terlipressin in Hospitalized Adults with Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI): Real-world Evidence in Patients by Transplant Waitlist Status6 Embargoed Until: Monday, May 5, 2025; 12:01 a.m. PDT Presenter: Kavish R. Patidar Session Type: Oral Presentation Session Title: SOA - Cirrhosis in the Obese Patient Session Date and Time: Monday, May 5, 2025; 4:45 – 5:00 p.m. PDT Abstract #4253811: A Comparative Analysis of Real-World HRS-AKI Treatment and Outcomes in the UK and US: Raw Clinical Data and Propensity Score-Matched Evidence7 Embargoed Until: Tuesday, May 6, 2025; 12:01 a.m. PDT Presenter : Stevan A. Gonzalez Session Type: Poster Session Session Title: Portal Hypertension and Non Bleeding Complications of Cirrhosis: Encephalopathy, Ascites, and HRS Session Date and Time: Tuesday, May 6, 2025; 12:30 – 1:30 p.m. PDT Abstract #4253534: Real-World Treatment and Outcomes in Hospitalized Patients with Hepatorenal Syndrome-Acute Kidney Injury and Alcohol-Associated Liver Disease8 Embargoed Until: Tuesday, May 6, 2025; 12:01 a.m. PDT Presenter: Robert Wong Session Type: Poster Session Session Title: Portal Hypertension and Non Bleeding Complications of Cirrhosis: Encephalopathy, Ascites, and HRS Session Date and Time: Tuesday, May 6, 2025; 12:30 – 1:30 p.m. PDT Abstract #4230360: Transforming Hepatorenal Syndrome-Acute Kidney Injury Treatment: A Win Ratio Analysis of Terlipressin Versus Placebo9 Embargoed Until: Tuesday, May 6, 2025; 12:01 a.m. PDT Presenter: Kavish R. Patidar Session Type: Poster Session Session Title: Portal Hypertension and Non Bleeding Complications of Cirrhosis: Encephalopathy, Ascites, and HRS Session Date and Time: Tuesday, May 6, 2025; 12:30 – 1:30 p.m. PDT Abstract #4253824: Improving the Benefit-to-risk Profile: Efficacy Outcomes in Patients with Hepatorenal Syndrome-Acute Kidney Injury When Selected According to the Terlipressin Prescribing Information10 Embargoed Until: Tuesday, May 6, 2025; 12:01 a.m. PDT Presenter: Michael P. Curry Session Type: Poster Session Session Title: Portal Hypertension and Non Bleeding Complications of Cirrhosis: Encephalopathy, Ascites, and HRS Session Date and Time: Tuesday, May 6, 2025; 12:30 – 1:30 p.m. PDT These analyses were sponsored by Mallinckrodt Pharmaceuticals. INDICATION AND LIMITATION OF USE TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit. IMPORTANT SAFETY INFORMATION WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ. Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%. Contraindications TERLIVAZ is contraindicated: In patients experiencing hypoxia or worsening respiratory symptoms. In patients with ongoing coronary, peripheral, or mesenteric ischemia. Warnings and Precautions Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms. Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure. Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks. Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions. Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus. Adverse Reactions The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea. Please click here to see full Prescribing Information, including Boxed Warning. ABOUT DIGESTIVE DISEASE WEEK® (DDW) Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at . ABOUT HEPATORENAL SYNDROME (HRS) Hepatorenal syndrome (HRS) is a life-threatening condition that occurs in people with advanced liver disease.3 HRS is classified into two distinct types – a rapidly progressive type that leads to acute renal failure where patients are typically hospitalized for their care (HRS-acute kidney injury (AKI)) and a more chronic type that progresses over weeks to months (HRS-chronic kidney disease (CKD)).3 HRS-AKI is estimated to affect more than 42,000 Americans annually, approximately 0.01% of the U.S. population,4 making it a very rare condition; and rates of HRS hospitalizations are increasing.5 If left untreated, HRS-AKI has a median survival time of less than two weeks and greater than 80% mortality within three months.2 ABOUT MALLINCKRODT Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The Company's Specialty Brands reportable segment's areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology and ophthalmology; neonatal respiratory critical care therapies; and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS This release contains forward-looking statements, including with regard to TERLIVAZ®, its potential to improve health and treatment outcomes, and its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt's recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with TERLIVAZ; and other risks identified and described in more detail in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Mallinckrodt's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. CONTACT Media Inquiries Green Room Communications 908-577-4531 [email protected] Investor Relations Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark, TERLIVAZ, and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2025 Mallinckrodt. US-2500183 04/25 References 1 TERLIVAZ® (terlipressin) for injection. [Prescribing Information]. Mallinckrodt Hospital Products Inc. 2023. 2 Flamm S.L., Brown K., Wadei H.M., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in the United States and the Potential of Terlipressin. Liver Transpl. 2021;27:1191-1202. 3 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at:. Accessed March 2025. 4 United States Census Bureau: Quick Facts. Available at: . Accessed March 2025. 5 Singh J., Dahiya D.S., Kichloo A., et al. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021;53:1. 2018-2024 doi.org/10/1080/07853890. 6 Patidar K.R., Barritt A.S. IV, Wong R., et al. Treatment and Outcomes of Terlipressin in Hospitalized Adults with Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI): Real-world Evidence in Patients by Transplant Waitlist Status. Abstract to be presented in an oral presentation at the Digestive Disease Week Meeting. May 2025. 7 Gonzalez S.A., Allegretti A.S., Chirikov V.V., et al. A Comparative Analysis of Real-World HRS-AKI Treatment and Outcomes in the UK and US: Raw Clinical Data and Propensity Score-Matched Evidence. Abstract to be presented in a poster presentation at the Digestive Disease Week Meeting. May 2025. 8 Wong R., Patidar K.R., Barritt A.S. IV, et al. Real-World Treatment and Outcomes in Hospitalized Patients with Hepatorenal Syndrome-Acute Kidney Injury and Alcohol-Associated Liver Disease. Abstract to be presented in a poster presentation at the Digestive Disease Week Meeting. May 2025. 9 Patidar K.R., Hernaez R., Cullaro G., et al. Transforming Hepatorenal Syndrome-Acute Kidney Injury Treatment: A Win Ratio Analysis of Terlipressin Versus Placebo. Abstract to be presented in a poster presentation at the Digestive Disease Week Meeting. May 2025. 10 Curry M.P., Pappas S.C., Marden M., et al. Improving the Benefit-to-risk Profile: Efficacy Outcomes in Patients with Hepatorenal Syndrome-Acute Kidney Injury When Selected According to the Terlipressin Prescribing Information. Abstract to be presented in a poster presentation at the Digestive Disease Week Meeting. May 2025. SOURCE Mallinckrodt plc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

March 27, 2025 -- Gyre Therapeutics (“Gyre”) (Nasdaq: GYRE), an innovative, commercial-stage biotechnology company with clinical development programs focusing on organ fibrosis, today announced the publication of the manuscript titled “Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B: Protocol for a Phase 3 Randomized Trial” in the Journal of Clinical and Translational Hepatology. This publication details the full protocol for the pivotal Phase 3 trial to support the use of hydronidone in Chinese patients with liver fibrosis associated with chronic hepatitis B (“CHB”). The published protocol outlines patient inclusion criteria, randomization and blinding processes, key assessments, and the statistical analysis plan. The randomized, double-blind, placebo-controlled, multicenter Phase 3 trial (NCT05115942) completed the enrollment of 248 patients across 44 clinical research hospitals in the People’s Republic of China (“PRC”) in October 2024. Patients were randomized 1:1 to receive either F351 or placebo in addition to entecavir antiviral basic therapy for CHB. The primary endpoint is a decrease in liver fibrosis (as measured by the Ishak Scoring System) by at least one stage after 52 weeks of treatment relative to baseline. The PRC’s National Medical Products Administration (“NMPA”) designated F351 as a “Breakthrough Therapy” in 2021. Gyre expects to report topline results from this Phase 3 trial in the second quarter of 2025. F351 is a next-generation anti-fibrotic compound and a structural analogue of Pirfenidone, the first approved treatment for idiopathic pulmonary fibrosis (“IPF”) in Japan, the European Union, the United States and the PRC. F351's dual mechanism has been shown to inhibit in vitro p38γ kinase activity and TGF-β1-driven collagen overproduction—both key drivers of liver fibrosis. F351 specifically targets hepatic stellate cells (“HSCs”), which are central to the progression of fibrosis. In preclinical studies, it has shown strong anti-proliferative and anti-fibrotic effects on HSCs. These effects have been validated across multiple in vivo models of liver fibrosis, including CCl4-induced liver fibrosis in mice, DMN- and HSA-induced liver fibrosis in rats, and a mouse model of MASH fibrosis (a form of MASH with fibrosis) induced by CCl4 plus a Western high-fat diet. Together, these results highlight F351’s potential as a differentiated treatment for liver fibrosis, with a unique mechanism and strong preclinical and clinical evidence supporting its advancement into later-stage development. Gyre Pharmaceuticals is a commercial-stage biopharmaceutical company committed to the research, development, manufacturing and commercialization of innovative drugs for organ fibrosis. Its flagship product, ETUARY® (Pirfenidone capsule), was the first approved treatment for IPF in the PRC in 2011 and has maintained a prominent market share (2024 net sales of $105.8 million). In addition, Gyre Pharmaceuticals is evaluating F351 in a Phase 3 clinical trial in CHB-associated liver fibrosis in the PRC, which is expected to readout topline data by Q2 2025. F351 received Breakthrough Therapy designation by the NMPA Center for Drug Evaluation in March 2021. Gyre Pharmaceuticals is also developing treatments for PD, DKD, COPD, PAH and ALF/ACLF. In October 2023, Gyre Therapeutics acquired an indirect majority interest in Gyre Pharmaceuticals (also known as Beijing Continent Pharmaceuticals Co., Ltd.). Gyre Therapeutics is a biopharmaceutical company headquartered in San Diego, CA, with a primary focus on the development and commercialization of F351 (Hydronidone) for the treatment of MASH-associated fibrosis in the U.S. Gyre’s development strategy for F351 in MASH is based on the company's experience in MASH rodent model mechanistic studies and CHB-induced liver fibrosis clinical studies. Gyre is also advancing a diverse pipeline in the PRC through its indirect controlling interest in Gyre Pharmaceuticals, including ETUARY therapeutic expansions, F573, F528, and F230. The content above comes from the network. if any infringement, please contact us to modify.

Trial to assess intensive care liver support system across 13 UK centers, led by UCL, Royal Free, Kings College and Queen Elizabeth BirminghamRapid co-primary endpoints measured over 10 and 28 days; readout Q1 2027Aims to resolve life-threatening condition and impact survival LONDON, March 21, 2025 (GLOBE NEWSWIRE) -- Yaqrit, a late clinical-stage company developing life-saving treatments for advanced liver diseases, announced today a major £2.2 million ($2.85 million) clinical research grant that will fund the development of its extracorporeal liver support device, DIALIVE (YAQ002) for advanced liver disease patients and move the device closer to UKCA and CE mark for marketing authorization. The device treats patients with Acute-on-Chronic Liver Failure (ACLF) grade 2 and 3, a life-threatening condition affecting patients with cirrhosis characterized by multiorgan failure and high risk of mortality. The grant covers the clinical and development costs of ALIVER 2.0, the randomized pivotal registration trial of Yaqrit’s YAQ002. The grant is from the UK’s largest funder of health R&D, the National Institute for Health and Care Research (NIHR), under their Invention for Innovation program (Award: NIHR206537). “The NIHR grant financing for YAQ002 enables Yaqrit to take this life-saving technology forward towards the market, as part of our mission to create value by helping patients with liver failure,” said Troels Jordansen, Chief Executive Officer of Yaqrit. “The prestige and resources of NIHR will accelerate Yaqrit’s development of YAQ002 bringing new hope to thousands of advanced liver patients who desperately need an effective treatment for ACLF.” Leading the study as co-principal investigators are Prof Banwari Agarwal and Dr Rohit Saha at the Royal Free Hospital, together with Prof Jalan at University College London (UCL), Dr Sameer Patel at Kings College Hospital London, and Dr Mansoor Bangash at the Queen Elizabeth Hospital, Birmingham. Nine other UK clinical centers specializing in the treatment of ACLF will also be involved in the recruitment of patients. Globally, ACLF affects up to 3.7 million patients with liver cirrhosis each year, including around 1.9 million grade 2 and 3 patients. Depending on severity, about 40-80% of patients die within 28 days. YAQ002 works by removing disease-causing toxins from patients’ blood, notably the ACLF-signatures of inflammatory mediators, and by exchanging dysfunctional albumin for fresh albumin. The device has already proved to be a safe and rapid way of resolving liver failure by allowing liver regeneration to occur. In a successful earlier Europe-wide study, ACLF was resolved approximately twice as frequently and significantly more rapidly during the 10-day treatment period in YAQ002-treated patients as in those on standard-of-care treatments. “This is extremely important news for patients within the UK and beyond with advanced liver disease whose current treatment options are severely limited,” said Rajiv Jalan, co-principal investigator, Professor of Hepatology from UCL Institute for Liver & Digestive Health and Yaqrit’s Founder. “Our goal is to demonstrate that we can resolve ACLF more often and/or faster than standard of care, and thereby impact both patients’ time in hospital and chances of survival.” Results of the trial are expected in Q1 2027, following formal ethical clearance and a patient recruitment period of around 18 months. The trial will recruit about 70 of the sickest patients -- those with multiple organ failure following liver disease (ACLF Grade 2 and Grade 3) -- who have a high risk (up to 80%) of dying unless they receive a liver transplant. Following enrollment, during a 10-day treatment period, those patients randomized to receive YAQ002 will receive up to 7 sessions of treatment. The kick-off meeting and first Investigator’s meeting were held on the 12th March 2025 at the Institute for Liver and Digestive Health, UCL. YAQ002 is being developed by Yaqrit’s subsidiary Cytox Life-Sciences. Contact Company Troels Jordansen Email: Troels@Yaqrit.com Tel: +31 6 1834 5326 Contact Investors Mary-Ann Chang Email: Mary-Ann@Yaqrit.com Tel: +44 7483 284 853 About Yaqrit Yaqrit is a clinical-stage company discovering and developing innovative treatments for patients with advanced liver disease at high risk of hospitalization and death. Yaqrit’s pipeline includes three novel therapeutics at phase 2-3 of development and two medical devices providing acute and chronic treatments for advanced cirrhosis and acute-on-chronic liver failure where there is an urgent need for more effective treatments. More information is available at www.Yaqrit.com About Decompensated Cirrhosis In over 10 million patients worldwide per year, liver cirrhosis progresses from an asymptomatic (compensated) form to the decompensated form at which point the liver can no longer undertake its usual functions. As a result, levels of ammonia in the blood can increase and have a toxic impact on the brain, causing hepatic encephalopathy. Patients with decompensated cirrhosis also become highly susceptible to bacterial infections because of immune dysfunction. Multiple organ failure becomes more common. These factors lead to increased morbidity with median survival falling from more than 12 years for compensated cirrhosis to about two years for decompensated cirrhosis. About Acute-on-Chronic Liver Failure Acute-on-Chronic Liver Failure (ACLF) is a life-threatening syndrome affecting patients with cirrhosis, characterized by intense systematic inflammation, organ failure and high short-term mortality. Globally, around 35% of 10.6 million patients with acutely decompensated cirrhosis have ACLF, rising to 65% among South Asia populations. Current outcomes for patients remain poor, with 58% mortality in the first 90 days. About NIHR The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by: Funding high quality, timely research that benefits the NHS, public health and social care;Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;Attracting, training and supporting the best researchers to tackle complex health and social care challenges;Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries. NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.