Albumin(Evolve Biologics, Inc.)

– A total of 11 scientific abstracts from Mallinckrodt's research for adults with HRS with rapid reduction in kidney function1 provide further insight into the clinical efficacy, safety, and real-world utility of TERLIVAZ treatment for appropriate patients – – Mallinckrodt's presence to include three oral presentations and one AASLD Poster of Distinction – DUBLIN, Nov. 8, 2023 /PRNewswire/ -- Mallinckrodt plc (OTCMKTS: MNKTQ), a global specialty pharmaceutical company, today announced the presentation of 11 scientific abstracts with findings from the latest clinical and health economics research with TERLIVAZ® (terlipressin) for injection for adult patients with hepatorenal syndrome (HRS) with rapid reduction in kidney function1 during the American Association for the Study of Liver Diseases (AASLD) 2023 Liver Meeting, taking place November 10-14, 2023 in Boston, MA. Continue Reading Video Showcasing Mallinckrodt Presence at AASLD View PDF HRS Infographic Experience the interactive Multichannel News Release here: Included among Mallinckrodt's breadth of data for adults with HRS with rapid reduction in kidney function1 are three oral presentations and one Poster of Distinction detailing research of clinical outcomes with TERLIVAZ2,3,4 and real-world health economics outcomes for TERLIVAZ-treated patients with comorbidities.5 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.6 HRS involving rapid reduction in kidney function1 is estimated to affect more than 35,000 Americans annually and rates of HRS hospitalizations are increasing.7,8 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. "It is essential to continue research into the relationship between TERLIVAZ treatment and key factors impacting clinical outcomes, such as concomitant treatments, comorbidities, and real-world care environments, to provide further insights into the continued use of TERLIVAZ for patients with this critical condition," said Khurram Jamil, MD, Vice President, Hepatology, Clinical Development & Critical Care. "We are thrilled to be able to share findings from our 11 scientific presentations at this year's AASLD Liver Meeting with the medical community – a testament to the breadth and depth of Mallinckrodt's commitment to expanding our collective knowledge of HRS to help physicians diagnose and treat HRS patients as early and effectively as possible." Highlights of Mallinckrodt's 11 scientific presentations at the AASLD 2023 Liver Meeting include: Three Oral Presentations: Findings from a pooled analysis of the three largest-ever prospective studies to assess the safety and efficacy of TERLIVAZ in patients with HRS type 1 (HRS-1) in the U.S. and Canada (CONFIRM, REVERSE, and OT-0401) evaluating the impact of mean arterial pressure on HRS reversal from baseline to end of treatment with TERLIVAZ (Abstract #224).2 Health economics outcomes from a decision-analytic model projecting the benefit of TERLIVAZ treatment among patients with alcohol-related cirrhosis and HRS (Abstract #80).5 An analysis of the clinical outcomes associated with concomitant albumin dosing with TERLIVAZ for the treatment of HRS-acute kidney injury (HRS-AKI) (Abstract #211).3 One AASLD Poster of Distinction: Results from a post hoc analysis of the CONFIRM, REVERSE, and OT-0401 trials assessing the relationship between mean arterial pressure and TERLIVAZ in HRS-AKI reversal (Abstract #3052-A).4 Please see a complete list of Mallinckrodt-sponsored abstracts to be presented at the 2023 AASLD Liver Meeting here. Abstracts can also be found on the 2023 AASLD Liver Meeting website. Mallinckrodt will also be present at the meeting with an interactive Medical Affairs booth in the exhibit hall (Location D2825) throughout the duration of the meeting. Data collected in retrospective, pooled, database, or post hoc analyses may have errors or omissions. Outcomes may be influenced by therapies not evaluated in the study and the clinical/health economic outcomes may not be solely attributable to TERLIVAZ. 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.6 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.6 HRS involving rapid reduction in kidney function1 is estimated to affect more than 35,000 Americans annually and rates of HRS hospitalizations are increasing.7,8 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.9,10 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; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website. 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 impact of Mallinckrodt's pending Chapter 11 cases; 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" section of Mallinckrodt's most recent Annual Report on Form 10-K 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 954-816-6003 [email protected] Investor Relations Daniel J. Speciale Senior Vice President, Finance and Chief Financial Officer, Specialty Generics 314-654-3638 [email protected] Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2023 Mallinckrodt. US-2300796 11/23 References 1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 2 Fricker ZP, et al. Improved Mean Arterial Pressure from Baseline to the End of Treatment with Terlipressin is Associated with Hepatorenal Syndrome Reversal: A Pooled Analysis of 3 Phase III Studies. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 3 Wong F, et al. Albumin Dosing with Terlipressin for the Treatment of HRS-AKI: A Double-Edged Sword. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 4 Cullaro G, et al. Understanding the Relationship Between Mean Arterial Pressure and Terlipressin in Hepatorenal Syndrome-Acute Kidney Injury Reversal: A Post Hoc Analysis of the CONFIRM, REVERSE, and OT-0401 Trials. Poster of Distinction to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 5 Mumtaz K, et al. Decision-Analytic Model to Project the Benefit of Terlipressin Treatment Among Patients with Alcohol-Related Cirrhosis and HRS. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 6 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed October 2023. 7 Data on file – Ref-06931. Mallinckrodt Pharmaceuticals. 8 Singh J, Dahiya DS, Kichloo A, Singh G, Khoshbin K, Shaka H. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021;53:1. doi.org/10/1080/07853890 9 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. . 10 Boyer TD, et al. Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. Gastroenterology. 2016;150:1579-1589. SOURCE Mallinckrodt plc

–Three scientific abstracts via one oral and two poster presentations detail the Company's latest clinical research findings on the therapeutic effect of TERLIVAZ for adults with HRS involving rapid reduction in kidney function1 – DUBLIN, Nov. 1, 2023 /PRNewswire/ -- Mallinckrodt plc (OTCMKTS: MNKTQ), a global specialty pharmaceutical company, today announced that three scientific abstracts evaluating treatment with TERLIVAZ® (terlipressin) for injection for adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function1 – including its impact on patient care, key HRS endpoints and patient comorbidity – will be presented at the American Society of Nephrology (ASN) Kidney Week 2023 Scientific Meeting in Philadelphia, Pennsylvania, taking place November 2-5, 2023. 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 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. Mallinckrodt's three scientific abstracts at ASN's Kidney Week 2023 Scientific Meeting, two of which will take place on November 2 and one on November 4, will be presented by Juan Carlos Q. Velez, MD, and Hani M. Wadei, MD. Juan Carlos Q. Velez, MD, will present findings from a post hoc analysis of the Phase III CONFIRM clinical trial exploring the incidence of HRS reversal in patients treated with TERLIVAZ plus albumin versus placebo plus albumin to determine if an improvement in serum creatinine of >30% was associated with improved clinical outcomes.3 The study evaluated the magnitude of improvement in serum creatinine level from baseline to the end of treatment, and its potential relationship with patient's length of intensive care unit stay and the incidence of renal replacement therapy, among other clinical measures.3 A pooled analysis of the results from the three largest prospective, randomized, placebo-controlled clinical studies in patients with HRS (OT-0401, REVERSE, and CONFIRM) will be presented by Hani M. Wadei, MD.4 The analysis assessed the role of TERLIVAZ plus albumin versus placebo plus albumin on HRS reversal in the subpopulation of patients with comorbidities of alcoholic hepatitis, mean arterial pressure of <70 mmHg and/or systemic inflammatory response syndrome.4 In an oral presentation, Hani M. Wadei, MD, will also present a post hoc analysis of the Phase III, randomized, placebo-controlled CONFIRM study evaluating the incidence, indications, and modes of renal replacement therapy used in the subgroup of patients with fluid overload, as determined by investigator assessment.5 Patients with fluid overload included those who reported hemodynamic edema and effusions.5 Additional information on these studies can be found below. "The CONFIRM clinical trial was the largest-ever prospective, randomized clinical trial of TERLIVAZ in patients with hepatorenal syndrome (HRS),1 and continues to offer new learnings and insights as reflected in the upcoming presentations at the American Society of Nephrology's Annual Meeting," said Khurram Jamil, Vice President, Hepatology, Clinical Development & Critical Care. "We're hopeful these findings will continue to inform the medical community's approach to diagnosis and clinical management of this critical condition, leading to better outcomes for HRS patients with rapid reduction in kidney function."1 These studies are sponsored by Mallinckrodt Pharmaceuticals and include: Abstract TH-PO052: Improvement in Serum Creatinine was Associated with Favorable Clinical Outcomes in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study3 Presenter: Juan Carlos Q. Velez, MD, Ochsner Health, New Orleans, LA, USA Session Type: Poster Presentation Presentation Location: Exhibit Hall, Pennsylvania Convention Center Session Date and Time: Thursday, November 2, 2023; 10:00 a.m. – 12:00 p.m. EDT Abstract TH-PO050: Terlipressin Therapy in Patients with HRS and Comorbidities: The North American Experience4 Presenter: Hani M. Wadei, MD, Mayo Clinic, Jacksonville, FL, USA Session Type: Poster Presentation Presentation Location: Exhibit Hall, Pennsylvania Convention Center Session Date and Time: Thursday, November 2, 2023; 10:00 a.m. – 12:00 p.m. EDT Abstract SA-OR03: Effect of Terlipressin Treatment on the Incidence of Renal Replacement Therapy in Patients with Hepatorenal Syndrome and Fluid Overload: A Post Hoc Analysis of the Phase 3 CONFIRM Study5 Presenter: Hani M. Wadei, MD, Mayo Clinic, Jacksonville, FL, USA Session Type: Oral Presentation Presentation Location: Room 118, Pennsylvania Convention Center Presentation Date and Time: Saturday, November 4, 2023; 4:48 – 4:57 p.m. EDT 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 35,000 Americans annually and rates of HRS hospitalizations are increasing.6,7 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.8 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; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website. 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 impact of Mallinckrodt's pending Chapter 11 cases; 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" section of Mallinckrodt's most recent Annual Report on Form 10-K 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 954-816-6003 [email protected] Investor Relations Daniel J. Speciale Senior Vice President, Finance and Chief Financial Officer, Specialty Generics 314-654-3638 [email protected] Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2023 Mallinckrodt. US-2300739 11/23 References 1 TERLIVAZ® (terlipressin) for injection. [Prescribing Information]. Mallinckrodt Hospital Products Inc. 2023. 2 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed September 14, 2023. 3 Velez JCQ, Mujtaba MA, Zhiwei Z, Elsiesy H, Jamil K. Improvement in Serum Creatinine was Associated with Favorable Clinical Outcomes in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study. Abstract to be presented at the American Society of Nephrology (ASN) 2023 Annual meeting. November 2023. 4 Wadei HM, Zhang Z, Alzubaidl M, Jamil K. Terlipressin Therapy in Patients with HRS and Comorbidities: The North American Experience. Abstract to be presented at the American Society of Nephrology (ASN) 2023 Annual meeting. November 2023. 5 Wadei HM, Mujtaba MA, Jamil K. Effect of Terlipressin Treatment on the Incidence of Renal Replacement Therapy in Patients with Hepatorenal Syndrome and Fluid Overload: A Post Hoc Analysis of the Phase 3 CONFIRM Study. Abstract to be presented at the American Society of Nephrology (ASN) 2023 Annual meeting. November 2023. 6 Data on file – Ref-06931. Mallinckrodt Pharmaceuticals. 7 Singh J, Dahiya DS, Kichloo A, Singh G, Khoshbin K, Shaka H. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021; 53:1. doi.org/10/1080/07853890 8 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