Hepatorenal Syndrome

– 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

The combined company is expected to be listed on the New York Stock Exchange. Credit: Anton Vierietin via Getty Images. Mallinckrodt Pharmaceuticals and Endo have agreed to merge in a $6.7bn deal, combining two pharmaceutical companies that recently emerged from bankruptcy proceedings tied to opioid litigation. According to the 13 March announcement, the merger will create a “larger, more diversified entity”, with Mallinckrodt shareholders holding a 50.1% stake and Endo shareholders receiving 49.9%, along with $80m in cash. Under the terms of the agreement, Mallinckrodt CEO Siggi Olafsson will serve as the president and chief executive of the combined company, while Endo director Paul Efron will take on the role of chairman of the board. Endo will continue to operate as a wholly owned subsidiary of Mallinckrodt, as per the 13 March announcement. This merger comes after both companies faced significant financial and legal challenges due to their involvement in the sale of opioid painkillers. The opioid crisis in the US has led to extensive litigation against pharmaceutical companies accused of fuelling widespread addiction and overdose deaths. Mallinckrodt and Endo were among those sued over allegations that they contributed to the crisis by misrepresenting the risks of opioid products. Mallinckrodt first filed for bankruptcy in 2020 after reaching a tentative $1.6bn settlement with 47 states, territories, and other claimants in the US over its opioid-related liabilities. The company filed for bankruptcy again in 2023 following declining sales of key products. Net sales of the company’s top-selling drug, Acthar – a gel used to treat certain autoimmune and skin diseases – dropped by $90.7m in 2023 from the previous year, as per the company financials. The Dublin-headquartered company emerged from bankruptcy in November 2023, having reduced its total funded debt by $1.9bn. In 2023, it also paid out $700m to victims of the opioid crisis to settle thousands of lawsuits for manufacturing a generic version of Oxycodone. Endo, headquartered in Pennsylvania, US, similarly filed for bankruptcy in 2022 due to opioid-related liabilities. The company agreed to pay $465m to the US government and $450m to state and municipal trusts to support opioid recovery programmes. The company also pleaded guilty to a misdemeanour related to its opioid marketing practices. Both companies have worked to reposition themselves as specialty pharmaceutical firms, divesting non-core businesses. Earlier this week, Endo sold its international pharma unit Paladin to Knight Therapeutics for up to $99m, while Mallinckrodt sold its Therakos division to private equity firm CVC Capital Partners for $925m in August 2024. Mallinckrodt now focuses on generics and specialty medicines, including Acthar Gel and Terlivaz (terlipressin) for hepatorenal syndrome. Endo’s portfolio includes Xiaflex (collagenase clostridium histolyticum) for Dupuytren’s contracture and Peyronie’s disease, as well as a range of generics and sterile injectables. As part of the merger – which is expected to close in H2 2025 – the generics and sterile injectables businesses of both companies will be spun off into a separate standalone entity upon deal completion. The new company will be listed on the New York Stock Exchange and is expected to generate approximately $3.6bn in revenue in 2025.

iStock, Dmitrii_Guzhanin Both Mallinckrodt and Endo have previously declared bankruptcy, linked to opioid-related lawsuits. Endo and Mallinckrodt—two drugmakers that have run into financial rough spots in recent years— will merge in a stock and cash transaction worth $6.7 billion, the companies formally announced Thursday. The news comes after reports of a business combination circulated on Wednesday, first reported by Bloomberg . As per the Thursday release, Endo will be folded into Mallinckrodt, which will then continue as the holding entity for the combined companies. Post-merger, the company will be listed on the New York Stock Exchange and is projected to generate around $3.6 billion in revenue this year. Ownership of the resulting entity will be split near-perfectly down the middle: Endo shareholders will own 49.9% of the resulting entity, while the remaining 50.1% will belong to Mallinckrodt shareholders. Siggi Olafsson, president and CEO of Mallinckrodt, will be CEO, president and board member of the merged business, while Paul Efron, currently an Endo Board member, will serve as Chair of the combined company’s Board. The deal should close in the second half of the year, pending regulatory clearances. The companies will combine and spin off their generics businesses into a separate entity pending Board approval. In October 2020, Mallinckrodt filed for Chapter 11 bankruptcy , which the company said would help it restructure its debt and allow it to weather “several billion dollars of otherwise unmanageable potential legal liabilities.” A few months earlier, Mallinckrodt had agreed “in principle” to a $1.6 billion settlement for alleged injuries related to many of its generic opioid products. In August 2023, the company announced a major restructuring support agreement with its biggest debtholders and with the opioid trust that was handling its settlement payouts. Mallinckrodt at the time also unveiled plans to another Chapter 11 bankruptcy, which a Delaware court approved of in October 2023 . Headquartered in Dublin, Ireland, Mallinckrodt is a specialty pharmaceuticals company that produces both branded and generic drugs. Perhaps its most notable branded product is Terlivaz, an intravenously injected vasopressin receptor agonist that in September 2022 became the first FDA-approved therapy for hepatorenal syndrome, kidney failure linked to liver cirrhosis. Endo has similarly run into financial difficulties due to opioid lawsuits. The pharma used to manufacture an opioid pain medication called Opana ER, which the FDA in June 2017 flagged for withdrawal due to safety risks associated with opioid overuse. In May 2024, the Justice Department hit Endo with a $1.086 billion fine —plus $450 million for criminal forfeiture—for violating the Federal Food, Drug and Cosmetic Act connected to the distribution of Opana ER. Endo filed for bankruptcy in August 2022 . On Tuesday, the company offloaded its international business to Knight Therapeutics for $84 million upfront and up to $15 million in future payments.