Liver Diseases, Alcoholic

Partnership agreement will be the first-ever co-marketing and sales collaboration for the ALZET Osmotic Pumps Portfolio and Associated Product Line in the U.S. and Canada Both companies will jointly market and commercialize the ALZET product line to customers over a multi-year period CUPERTINO, Calif. , March 4, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX), today announced that it has entered into a co-marketing and collaboration agreement with Charles River Laboratories for the ALZET® Osmotic Pumps Portfolio and Associated Product Line in the U.S. and Canada. Charles River is a highly respected, global provider of drug discovery and non-clinical development solutions. Charles River Research Models & Services (RMS) sales and marketing teams will collaborate with DURECT to jointly market and commercialize the ALZET product line to existing and new customers in the pharmaceutical industry and academic laboratories over a multi-year period. Charles River RMS will provide dedicated marketing resources and collaborate with DURECT to develop and roll out a broad range of sales and marketing initiatives for ALZET. DURECT will remain responsible for manufacturing, marketing support, order fulfillment and customer billing. "The DURECT and Charles River RMS teams are excited by this synergistic commercial partnership," said James E. Brown, D.V.M., President and CEO of DURECT. "Both teams look forward to collaborating to broaden awareness, promote and expand ALZET sales across the U.S. and Canada." About ALZET Osmotic Pumps The ALZET product line consists of miniature implantable pumps and a range of accessories for experimental research in mice, rats, and other laboratory animals. ALZET pumps continuously deliver drugs, hormones, and other test agents at controlled rates for durations ranging from 1 day to 6 weeks. They eliminate the need for external connections, frequent handling, or repeated dosing. The wide use and broad application of the ALZET product line is evidenced by more than 22,000 references in the scientific literature. ALZET pumps are neither approved nor intended for human use. For more information about the ALZET product line, please visit . About DURECT Corporation DURECT is a late-stage biopharmaceutical company pioneering the development of epigenetic therapies that target dysregulated DNA methylation to transform the treatment of serious and life-threatening conditions, including acute organ injury and cancer. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which FDA has granted a Fast Track Designation. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in the United States. For more information about DURECT, please visit and follow us on X (formerly Twitter) at . DURECT Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: the potential for larsucosterol to demonstrate a reduction in mortality or liver transplant in patients with AH and to save lives, our plans to meet with the FDA to review the results of AHFIRM trial and the Phase 3 registration trial design in the first quarter of 2024, the potential FDA or other regulatory approval of larsucosterol for the treatment of AH, the commercialization of POSIMIR by Innocoll, the potential to develop larsucosterol for AH, NASH or other indications, and the potential benefits, if any, of our product candidates. Actual results may differ materially from those contained in the forward-looking statements contained in this press release, and reported results should not be considered as an indication of future performance. The potential risks and uncertainties that could cause actual results to differ from those projected include, among other things, the risk that future clinical trials of larsucosterol do not confirm the results from subset analyses of the AHFIRM trial, including geographic or other segmentation, or of earlier clinical or pre-clinical trials, or do not demonstrate the safety or efficacy of larsucosterol in a statistically significant manner, the risk that the FDA or other government agencies may require additional clinical trials for larsucosterol before approving it for the treatment of AH, risks that Innocoll may not commercialize POSIMIR successfully, and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our need or desire for additional financing, our ability to meet the minimum bid price for continued listing on Nasdaq, our ability to obtain capital to fund our operations and expenses and our ability to continue to operate as a going concern. Further information regarding these and other risks is included in DURECT's most recent Securities and Exchange Commission (SEC) filings, including its annual report on Form 10-K for the year ended December 31, 2022 and quarterly report on Form 10-Q for the quarter ended September 30, 2023, when filed, under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . All information provided in this press release and in the attachments is based on information available to DURECT as of the date hereof, and DURECT assumes no obligation to update this information as a result of future events or developments, except as required by law. NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. Larsucosterol is an investigational drug candidate under development and has not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities for any indication. SOURCE DURECT Corporation

sNDA intended to satisfy post-marketing requirements to confirm a clinical benefit in patients with PBC Precedent-setting submission includes data from post-marketing studies COBALT and Study 401 as well as real-world evidence from a claims database and patient registries FDA has assigned a PDUFA target action date of October 15, 2024 MORRISTOWN, N.J., Feb. 29, 2024 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc., a biopharmaceutical company and wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for Ocaliva for the treatment of individuals with primary biliary cholangitis (PBC). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 15, 2024. In this communication, the agency informed Intercept that they are planning to hold an Advisory Committee meeting to discuss the application. “The sNDA data submission asserted that, with more than seven years on the market and more than 40,000 patient-years of post-marketing experience in PBC, Ocaliva is the only second-line therapy that has multiple published analyses of registry data and real-world evidence showing significant effect on transplant-free and decompensation-free survival in people living with PBC,” said Paul Nitschmann, M.D., Senior Vice President of Regulatory Affairs at Intercept. “We are pleased that the FDA has filed the submission and look forward to continued, constructive interactions with the agency, including discussing our precedent-setting application during the forthcoming Advisory Committee meeting.” Ocaliva received accelerated approval in 2016 and is indicated for the treatment of adult patients living with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The precedent-setting sNDA for Ocaliva is intended to satisfy the post-marketing requirements to confirm a clinical benefit in patients with PBC. The sNDA is supported by data from the Company’s post-marketing requirement studies COBALT and Study 401 as well as real-world evidence from a U.S. claims database and international PBC patient registries. Intercept and Alfasigma remain committed to supporting people living with PBC and look forward to advancing discussions with the agency. About Primary Biliary Cholangitis Primary biliary cholangitis (PBC) is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant, or death. About Ocaliva® (obeticholic acid) OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Contraindications OCALIVA is contraindicated in patients with: decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event compensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) complete biliary obstruction Warnings and Precautions Hepatic Decompensation and Failure in PBC Patients with Cirrhosis Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among post-marketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was 4 months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment. Severe Pruritus Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after 1 year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions (≥5%) are: pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. Drug Interactions Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of OCALIVA. If taking a bile acid binding resin, take OCALIVA at least 4 hours before or 4 hours after taking the bile acid binding resin, or at as great an interval as possible. Warfarin The International Normalized Ratio (INR) decreased following coadministration of warfarin and OCALIVA. Monitor INR and adjust the dose of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin. CYP1A2 Substrates with Narrow Therapeutic Index Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA. Inhibitors of Bile Salt Efflux Pump Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin. Please click here for Full Prescribing Information, including Boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or . About Intercept Intercept is a biopharmaceutical company and a wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to Ocaliva in the U.S. market. For more information, please visit or connect with the Company on LinkedIn, Threads, and X (formerly Twitter). Contact For more information about Intercept, please contact: For media: media@interceptpharma.com

Survodutide has potential to become best-in-class treatment for metabolic dysfunction-associated steatohepatitis (MASH)*, after meeting its primary and key secondary endpoint following 48 weeks of treatment versus placebo in a Phase II trial Survodutide, a novel glucagon/GLP-1 receptor dual agonist, has demonstrated efficacy in people with obesity1, and statistically significant results in MASH2 suggest the potential to lead to clinically meaningful benefits across the cardiovascular, renal, and metabolic spectrum Full data from the Phase II trial will be presented in the coming months Boehringer Ingelheim today announced that up to 83.0% of adults treated with survodutide (BI 456906) achieved a statistically significant improvement of metabolic dysfunction-associated steatohepatitis (MASH) versus placebo (18.2%) in a Phase II trial [response difference: 64.8% (CI 51.1% - 78.6%), p<0.0001].2 The trial met its primary endpoint with survodutide reaching a biopsy-proven improvement in MASH after 48 weeks, without worsening of fibrosis stages F1, F2 and F3 (mild to moderate or advanced scarring).2 Survodutide also met all secondary endpoints, including a statistically significant improvement in liver fibrosis.2 Full data will be presented in the coming months. Survodutide has the potential to become a best-in-class treatment for MASH, a liver disease connected with other cardiovascular, renal, and metabolic conditions.3,4,6 Survodutide is a glucagon/GLP-1 receptor dual agonist with a novel mechanism of action, and the first to show this level of benefit in a Phase II MASH trial.2,7 The glucagon agonist component in survodutide has the potential to increase energy expenditure,7and has a direct impact in the liver which potentially contributes to the improvement of fibrosis.2 The GLP-1 agonist component decreases appetite while increasing fullness and satiety.7,8 “I am thrilled to see these statistically significant results from the Phase II trial of survodutide in MASH and fibrosis. These data position survodutide as a potential leading treatment for a population with great unmet medical needs, and will bring hope to people living with MASH and with fibrosis,” said Dr. Arun Sanyal, M.D., Professor of Medicine, Physiology and Molecular Pathology at Virginia Commonwealth University School of Medicine, and Principal Investigator of the trial. “I am looking forward to sharing further detail on key secondary endpoints, including the percentage of adults who saw an improvement in fibrosis, at a congress in the first half of this year.” “These MASH results show survodutide has potential to become a best-in-class treatment, and we believe its true differentiator is the action of the glucagon receptor agonism which works directly on the liver,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “In order to bring this potential treatment to the more than 1 billion people affected by interconnected cardiovascular, renal, metabolic diseases, we will move forward as quickly as possible in MASH. We are also progressing with survodutide in other related conditions, having already initiated our Phase III clinical trial program for obesity.” The liver governs the body’s metabolism and consequently plays an important role in the cardiovascular, renal and metabolic system.9 MASH is a progressive disease impacting more than 115 million people worldwide10, caused by inflammation of the liver that can lead to fibrosis.11 Severe tissue scarring in the liver (cirrhosis) can substantially increase the risk of end-stage liver disease and liver cancer,5 for which a liver transplant may be the only treatment option.12 MASH is predicted to be the leading cause of liver transplantation by 2030,13 placing significant financial strain on healthcare systems.14,15 MASH can also impact a person’s quality of life, relationships, and capacity to work.16 Despite these burdens, targeted therapies are lacking and there are currently no approved licensed medicines. The double-blind, placebo-controlled Phase II trial studied three doses of survodutide at 2.4 mg, 4.8 mg, and 6.0 mg.17 Top-line results demonstrated an improvement in MASH, at all doses explored in the trial.2 Treatment with survodutide did not show unexpected safety or tolerability issues, including at the higher dose of 6.0mg.2 Today’s news builds on U.S. Food and Drug Administration (FDA) Fast Track Designation for survodutide in 2021,18 followed by the European Medicines Agency (EMA) granting access for survodutide to the Priority Medicine (PRIME) Scheme for MASH with fibrosis in November last year.19 These processes are designed to help expedite the review of drugs to treat serious conditions and fill an unmet need, with the intention of bringing important new drugs to patients earlier. Survodutide is also being evaluated in five Phase III studies for people living with overweight and obesity, among key sub-populations.20 SYNCHRONIZE-1 and SYNCHRONIZE-2 sub-populations include people living with comorbidities, without and with type 2 diabetes, respectively.20 The SYNCHRONIZE-CVOT trial sub-population includes people living with cardiovascular disease, chronic kidney disease, or with risk factors for cardiovascular disease.20 As well as this, Boehringer Ingelheim is exploring survodutide in Phase III trials in Japan (SYNCHRONIZE-JP) and in China (SYNCHRONIZE-CN) for sub-populations of people living with obesity.21,22 Use of MASH terminology *Boehringer Ingelheim’s Phase II trial is registered on clinicaltrials.gov as ‘A Study to Test Safety and Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3)’. This trial was registered prior to a 2023 update in nomenclature made by a number of multinational liver societies including EASL, AASLD and ALEH.23 Their recommendation was to update non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD), and to update non-alcoholic steatohepatitis (NASH) with metabolic dysfunction-associated steatohepatitis (MASH).23 The global liver community stated that the name changes reflect an affirmative, non-stigmatizing name and diagnosis that can be used around the world to improve research and funding into these conditions.23 An independent committee of experts external to this process made the final recommendations of the acronyms.23 To reflect these recommendations, Boehringer Ingelheim has adopted the use of MASH to describe this Phase II trial. About metabolic dysfunction-associated steatohepatitis (MASH) MASH is a chronic and progressive liver disease caused by a build-up of fat in the liver,11,24,25 and is a more severe form of metabolic dysfunction-associated steatotic liver disease (MASLD).26 Approximately 20-30% of people living with MASLD go on to develop MASH,27 and the number of MASH cases is predicted to rise by 63% between 2015 and 2030, from 16.5 million to 27.0 million cases.12 MASH is a disease closely associated with connected cardiovascular, renal, and metabolic diseases,6,28 and it is estimated that 34% of people living with obesity also have MASH.29 MASH also represents the fastest growing cause for liver transplantation in Western countries.14 MASH severity is assessed using a scale that ranges from F0 to F4, which measures the level of fibrosis (scarring):30 F0-F1: indicates no or mild fibrosis F2-3: indicates moderate or advanced fibrosis F4: indicates cirrhosis About the trial (NCT04771273) This is a Phase II, randomized double-blind placebo-controlled dose-finding trial of 295 participants that evaluates weekly subcutaneous injections of survodutide in people living with MASH and fibrosis (F1-F3) among adults both with and without type 2 diabetes.17 The primary endpoint of trial is the percentage of participants achieving histological improvement of MASH without worsening of fibrosis after 48 weeks of treatment.17 A histological improvement of MASH is defined as a decrease of ≥2 points on the Non-alcoholic Fatty Liver Disease Activity Score (NAS – total score ranges from 0-8), including ≥1 point decrease in NASH sub-score for lobular inflammation or ballooning, and no increase in fibrosis stage.17 The NAS represents the sum of scores for steatosis (a build-up of fat in the liver31), lobular inflammation (inflammatory cells32) and ballooning (a type of liver cell degeneration33). Secondary outcome measures include:17 At least 30% relative reduction in liver fat content after 48 weeks of treatment compared to baseline Absolute and relative change of liver fat content from baseline after 48 weeks of treatment Improvement of fibrosis, defined as at least one stage decrease in fibrosis stage after 48 weeks of treatment Absolute change from baseline in total score for NAS after 48 weeks of treatment The trial consisted of dose escalation to either 2.4mg, 4.8mg and 6.0mg treatment groups for up to 24 weeks, and dose maintenance for 24 weeks.17 About survodutide (BI 456906) Survodutide is a glucagon/GLP-1 receptor dual agonist that activates both the glucagon and GLP-1 receptors, which are critical to controlling metabolic functions.7 Co-invented by Boehringer Ingelheim and Zealand Pharma, survodutide is part of Boehringer Ingelheim’s research and development portfolio in the cardiovascular, renal, and metabolic disease areas. Survodutide was granted U.S. FDA Fast Track Designation in May 2021 for the treatment of MASH and fibrosis,18 and it was accepted to the EMA PRIME scheme in November 2023.19 Boehringer is also studying survodutide in a 2-part Phase I trial among people cirrhosis (F4) and varying degrees of liver dysfunction.34 The purpose of Part 1 is to find out whether cirrhosis (F4) and varying degrees of liver dysfunction influences how survodutide is taken up in the body, and the purpose of Part 2 is to find out whether having cirrhosis (F4) and varying degrees of liver dysfunction influences how people with overweight and obesity tolerate survodutide treatment for 28 weeks.34 Survodutide is also being evaluated in five Phase III studies (SYNCHRONIZE-1, SYNCHRONIZE-2, SYNCHRONIZE-CVOT) for people living with overweight and obesity.20 Sub-populations for SYNCHRONIZE-1 and SYNCHRONIZE-2 include patients with comorbidities, without and with type 2 diabetes, respectively.20 The sub-population for SYNCHRONIZE-CVOT includes patients with cardiovascular disease, chronic kidney disease, or with risk factors for cardiovascular disease.20 As well as this, Boehringer Ingelheim is exploring survodutide in Phase III trials in Japan (SYNCHRONIZE-JP) and in China (SYNCHRONIZE-CN) for sub-populations of people living with obesity.21,22 Both trials explore the relative change in liver fat from baseline to week 76 when treated with survodutide versus placebo, as a key secondary endpoint.21,22 About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at (UK and Ireland) or (rest of world). Boehringer Ingelheim’s Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. See the release on the Boehringer Ingelheim's website. References 1Boehringer Ingelheim. Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide. Available at: . Last accessed: February 2024. 2Boehringer Ingelheim. Top-line Results From A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3). Data on file. 3Younossi, Z.M., et al. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016; 64: 73-84. 4Godoy-Matos AF, Silva Júnior WS, Valerio CM. NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020 Jul 14;12:60. doi: 10.1186/s13098-020-00570-y. 5Tesfay M, Goldkamp WJ, Neuschwander-Tetri BA. NASH: The Emerging Most Common Form of Chronic Liver Disease. Mo Med. 2018 May-Jun;115(3):225-229. 6Musso G, et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul 22;11(7):e1001680. doi: 10.1371/journal.pmed.1001680. 7T. Zimmerman et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism. 2022;66:101633. doi: 10.1016/j.molmet.2022.101633. 8Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014 Sep;15(3):181-7. doi: 10.1007/s11154-014-9289-5. 9Rui L. Energy metabolism in the liver. Compr Physiol. 2014 Jan;4(1):177-97. doi: 10.1002/cphy.c130024 10British Liver Trust. International NASH Day. Available at: . Last accessed: February 2024. 11Ramai D, Facciorusso, et al. Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease. Cells. 2021 Dec 2;10(12):3401. doi: 10.3390/cells10123401. 12Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018; 67:123–133. doi: 10.1002/hep.29466. 13Tana C, Ballestri S, Ricci F, et al. Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications. Int J Environ Res Public Health. 2019; 16. doi: 10.3390/ijerph16173104. 14Khalil A, et al. New Developments and Challenges in Liver Transplantation. J Clin Med. 2023 Aug 27;12(17):5586. doi: 10.3390/jcm12175586. 15Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep. 2020 Oct 9;2(6):100192. doi: 10.1016/j.jhepr.2020.100192. 16Geier, A., et al. Real-World Burden of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2021 19: 1020-29.e7. 17ClinicalTrials.gov. A Study to Test Efficacy of BI456906 in Adults With Non-alcoholic Steatohepatitis (NASH) and Fibrosis (F1-F3). Available at: . Last accessed: February 2024. 18Boehringer Ingelheim. Boehringer Ingelheim and Zealand Pharma Received FDA Fast Track Designation for Investigational Treatment for NASH. Available at: . Last accessed: January 2024. 19European Medicines Agency. December 2023. List of medicines currently in PRIME scheme. Available at: . Last accessed: February 2024. 20Phase III studies to investigate survodutide for people living with obesity and overweight, with and without diabetes, cardiovascular disease and chronic kidney disease. Available at . Last accessed: February 2024. 21Clinicaltrials.gov. A Study to Test Whether BI 456906 Helps Japanese People Living With Obesity Disease (SYNCHRONIZE™JP). Available at: . Last accessed: February 2024. 22Clinicaltrials.gov. A Study to Test Whether BI 456906 Helps Chinese People Living With Overweight or Obesity to Lose Weight. Available at: . Last accessed: February 2024. 23EASL. 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