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– Pooled analysis from Phase 3 clinical trials highlights liver transplant rates in adult patients with HRS with rapid reduction in kidney function treated with TERLIVAZ1 – DUBLIN, Oct. 26, 2024 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, today announced a poster presentation on TERLIVAZ® (terlipressin) for injection in patients with hepatorenal syndrome (HRS) with rapid reduction in kidney function1 at Kidney Week 2024, the annual meeting of the American Society of Nephrology (ASN) taking place in San Diego from October 23-27, 2024. 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 an acute and life-threatening condition requiring hospitalization.2 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually, approximately 0.01% of the U.S. population,3 making it a very rare condition; and rates of hospitalizations are increasing.4 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. The poster presentation highlights a pooled analysis of data from the CONFIRM and REVERSE Phase 3 placebo-controlled trials of TERLIVAZ.5 The analysis examined the rates of hepatorenal syndrome-acute kidney injury (HRS-AKI) reversal, renal replacement therapy (RRT), and liver transplant (LT) among a subpopulation of patients listed for LT at baseline who met FDA label guidelines for treatment with TERLIVAZ (SCr <5 mg/dL, ACLF grade 0–2, and MELD score <35).5 In this patient subpopulation, treatment with TERLIVAZ increased the rate of HRS-AKI reversal and reduced the need for RRT at all time points assessed.5 The increase in HRS-AKI reversal with TERLIVAZ did not negatively impact the LT rate in patients listed for LT at baseline.5 The rate of HRS-AKI reversal was 43% in the TERLIVAZ group (n=53) and 20% in the placebo group (n=35).5 The rate of RRT in the TERLIVAZ and placebo groups was 28% and 46% by Day 30; 32% and 54% by Day 60; and 36% and 54% by Day 90, respectively.5 The LT rate was similar in the TERLIVAZ and placebo groups at all time points assessed: 53% and 51% by Day 30; 66% and 57% by Day 60; and 66% and 63% by Day 90, respectively.5 The limitations of this study include, but are not limited to, small sample sizes, variables in methodology, and possible errors and omissions within the data sets.5 "This analysis of data from our Phase 3 trials furthers our understanding of the appropriate patient subpopulations and the potential impact of treatment on liver transplantation rates," said Peter Richardson, MRCP (UK), Executive Vice President & Chief Scientific Officer. "For these critically ill patients with HRS-AKI, a liver transplant is the definitive treatment, and we know there are significant challenges associated with RRT; which makes continued research important." This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below: Poster #PO0102-2: Hepatorenal syndrome-acute kidney injury reversal and liver transplant rates in patients treated with terlipressin5 Presenter: Justin Belcher Session Type: Poster Presentation Session Title: AKI: Clinical, Outcomes, and Trials - Management Session Date and Time: Saturday, October 26, 2024; 10:00 a.m. – 12:00 p.m. PT 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 HEPATORENAL SYNDROME (HRS) Hepatorenal syndrome (HRS) involving rapid reduction in kidney function1 is an acute and life-threatening condition that occurs in people with advanced liver disease.2 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 and a more chronic type that progresses over weeks to months.2 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually, approximately 0.01% of the U.S. population,3 making it a very rare condition; and rates of HRS hospitalizations are increasing.4 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of less than two weeks and greater than 80 percent mortality within three months.6 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, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; 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. ©2024 Mallinckrodt. US-2400773 10/24 References 1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 2 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed October 2024. 3 United States Census Bureau: Quick Facts. Available at: . Accessed October 2024. 4 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. 5 Belcher J.M., Regner K.R., Mujtaba M.A., et al. Hepatorenal syndrome-acute kidney injury reversal and liver transplant rates in patients treated with terlipressin. Abstract to be presented at the American Society of Nephrology (ASN) 2024 Annual meeting. October 2024. 6 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. . 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

There's no current therapy approved to specifically treat refractory ascites, a common complication of liver cirrhosis. Even after raising $21 million in equity last week, BioVie is still axing the biotech’s “most de-risked program,” a phase 3-ready investigational infusion for patients with refractory ascites, a common complication of liver cirrhosis. The Nevada-based biotech has terminated a phase 2b trial evaluating BIV201 for refractory ascites after half of the intended patients were enrolled, according to a March 11 release. The trial had 15 patients at the time of termination, according to ClinicalTrials.gov.  BIV201 is a vasopressin V1 receptor agonist made of terlipressin acetate, the former of which is marketed under the name Terlivaz to improve kidney function for adults with hepatorenal syndrome. The FDA granted BIV201 orphan designation for ascites in 2016 and then fast-track status a year later. Currently, there's no approved treatment specifically for the condition. Data showed that BIV201 reduced ascites fluid buildup by over 50% in those that had completed treatment, BioVie said. While many biotechs shutter high-risk programs, BioVie dubbed BIV201 their “most de-risked program,” in a March 11 news release. The biotech added that BIV201 “unfortunately is a program that will take two years to complete.” “We look forward to partnering this program with a company interested in developing the first potential treatment for ascites and related complications potentially at an earlier stage of cirrhosis,” BioVie CEO Cuong Do said in the release. The company has already met with the FDA about designing a phase 3 study for the ascites candidate. Pending partnership funding, the phase 3 trial is set up to focus on cirrhotic patients with ascites who have experienced an acute kidney injury. The discontinuation comes on the heels of a $21 million equity financing round that will be used to help fund BioVie’s NE3107 as a potential first-line monotherapy in Parkinson’s disease. A phase 2b trial assessing the experimental oral therapy is set to launch this summer.  Just a few months ago, BioVie reported that a phase 3 trial assessing NE3107 in Alzheimer’s disease failed to hit the main goal, though the biotech blamed "protocol deviations" at several clinical trial sites for the failure and claimed that the evaluable data still shows the candidate improves cognitive function. BioVie had enrolled 439 patients across 39 trial sites, but “found significant deviation from protocol and Good Clinical Practice violations at 15 sites” and had to exclude the patients from analysis, meaning the study failed to hit the co-primary endpoints assessing cognition and function.   The company is now creating a once-daily formulation of NE3107 to use in a repeat of the phase 3 trial for patients with mild to moderate Alzheimer’s. The new formulation is expected to be ready in early-to-mid 2025. “We have great hopes for the Alzheimer’s program, but resources and the expected availability of a once-daily version of NE3107 makes delaying a year the best solution for patients and shareholders,” said Do.

REDWOOD CITY, Calif.--( BUSINESS WIRE )--Ocelot Bio, Inc., a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics to treat complications of end-stage liver disease (ESLD), today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its lead candidate OCE-205 for the treatment of ascites due to all etiologies except cancer. “The FDA granting Orphan Drug Designation for OCE-205 in ascites is validation of the tremendous need for improved therapies offering novel approaches for patients and supports our clinical focus on this important indication,” said Lise Kjems, M.D., Ph.D., chief medical officer at Ocelot Bio. “This milestone serves as a catalyst as we work with patients, healthcare professionals and health authorities to pave a brighter path forward for these patients who have limited treatment options. We are well positioned to further advance our clinical development program for OCE-205 and look forward to progressing this program in ascites.” Ascites is the abnormal accumulation of fluid within the peritoneal cavity of the abdomen and the hallmark of progression into the decompensated phase of cirrhosis. Data suggest that approximately 400,000 people live with ascites, with 60,000 refractory to standard-of-care treatment and who require much more aggressive treatment approaches. 1,2 Current treatments for ascites are limited, are often invasive procedures and may come with significant risks and burden for patients, underscoring the critical need for novel advancements that improve outcomes for those suffering from this devastating condition. Ocelot Bio plans to initiate clinical studies of OCE-205 in refractory ascites in 2024. The FDA grants Orphan Drug Designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. Orphan Drug Designation provides Ocelot Bio certain benefits, including financial incentives to support clinical development and the potential for up to seven years of market exclusivity for the drug for the designated orphan indication in the U.S. if the drug is ultimately approved for its designated indication. This is the second Orphan Drug Designation for OCE-205, which previously received the designation in hepatorenal syndrome. About OCE-205 Ocelot Bio’s lead asset, OCE-205, is a therapeutic peptide with a differentiated mechanism of action that has potential for improving outcomes for patients with complications of end-stage liver disease (ESLD). OCE-205’s innovation emanates from its design as a mixed agonist-antagonist peptide selective for the vasopressin 1a (V1a) receptor with no vasopressin 2 (v2) receptor activity at drug concentrations well above those used in treating ESLD. By virtue of its mixed V1a agonist/antagonist activity, OCE-205 treatment is designed to relieve portal hypertension while offering a capped maximal efficacy that avoids excessive vasoconstriction seen with full agonists, that leads to ischemic injury and potentially other serious adverse events such as respiratory failure. By eliminating V2 activity, OCE-205 treatment is designed to avoid fluid retention and overload. A Phase 2 clinical trial has completed enrollment to evaluate OCE-205 for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI) ( NCT05309200 ), and clinical studies for ascites are expected to initiate in 2024. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for OCE-205 in the treatment of hepatorenal syndrome in 2022 and in ascites in 2023. About Ocelot Bio Ocelot Bio is a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics designed to significantly improve outcomes for patients with liver disease. The company’s lead clinical candidate, OCE-205, is a peptide therapeutic with a mechanism of action designed to selectively target complications of portal hypertension, such as hepatorenal syndrome with acute kidney injury (HRS-AKI) and ascites, serious and life-threatening consequences of end-stage liver disease (ESLD). The company was founded by leading experts in peptide therapeutic development and is backed by a strong syndicate of investors including Venrock, RA Capital Management and Vivo Capital. For more information, visit www.ocelotbio.com . References 1 Siqueira F, et al. Gastroenterol Hepatol (N Y) . 2009;5(9):647-656. 2 Orman, et al. JAMA Netw Open . 2019;2;2(10):e1913673.