MYO5B

Late-breaking poster presentation features LIVMARLI® data showing long-term maintenance of response in patients with PFIC Four poster presentations highlight LIVMARLI PFIC data as well as a poster with proof-of-concept trial data from volixibat study in intrahepatic cholestasis of pregnancy FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced new data from its LIVMARLI and volixibat programs presented at The Liver Meeting®, the American Association for the Study of Liver Diseases (AASLD) annual meeting in Boston, Massachusetts. Data were presented from the Phase 3 MARCH study and MARCH-ON extension evaluating the efficacy and safety of LIVMARLI in patients with progressive familial intrahepatic cholestasis (PFIC) as well as the Phase 2 OHANA study evaluating the efficacy and safety of volixibat in patients with intrahepatic cholestasis of pregnancy (ICP). MARCH was the largest and most genetically diverse trial of PFIC to date, enrolling patients with deficiencies of BSEP, FIC1, MDR3, TJP2, AND MYO5B, as well as those clinically diagnosed with PFIC but without a known genetic variant. “PFIC is a chronic, debilitating cholestatic liver disease characterized by elevated bile acids and pruritus so severe that patients can be listed for liver transplant even in the absence of disease progression. We are excited to share the long-term benefits observed across multiple measures including reductions in pruritus, serum bile acids, improved liver health and growth for patients with PFIC treated with maralixibat in multiple genetic types which have not previously been reported,” said Pam Vig, PhD, head of research and development at Mirum. “We are also pleased to share the findings from the OHANA study of volixibat in patients with ICP, showing a clear impact of volixibat on serum bile acids and pruritus in this cholestatic setting.” A summary of these data presented is featured below. Full presentations can be found within the Publications and Presentations section of Mirum’s website. Late-breaker Poster Presentation Poster 5048-C: Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study The MARCH-ON extension study evaluated the long-term efficacy and safety of maralixibat in patients with PFIC who received maralixibat in the original MARCH study for 26 weeks and continued for up to two years and those who were on placebo who went on to receive maralixibat for up to one year. Significant and sustained improvements in pruritus severity, serum bile acid (sBA) levels, total bilirubin, and growth were observed with up to two years of maralixibat treatment across the broadest range of genetic PFIC types studied to date. The placebo-maralixibat group demonstrated rapid (as early as three weeks) and significant improvements in pruritus severity and sBA levels similar to those observed in the original MARCH maralixibat group. No new safety signals were observed. The most common treatment emergent adverse events were GI, occurred early in treatment, and were mild and transient in nature. These data suggest overall improved liver health with maralixibat treatment in patients with PFIC that can be maintained long-term. Other Poster Presentations Poster 4602-C: Improvements in pruritus with maralixibat are associated with improved quality of life for patients with progressive familial intrahepatic cholestasis: Data from the MARCH-PFIC trial Pruritus is known to be one of the most burdensome symptoms of PFIC, occurring in the majority of patients and leading to sleep disturbance, self-mutilation, and decreased school performance, further contributing to impaired quality of life. An exploratory endpoint in the MARCH study was to evaluate if a clinically significant reduction in pruritus following treatment with maralixibat was associated with an improvement in quality of life. These data demonstrated that clinically significant reductions in pruritus were associated with meaningful improvements in quality of life, as evaluated across several domains. The maralixibat group demonstrated significant differences between pruritus responders and non-responders for PedsQL, PedsQL-SF, PedsQL-PF, and a trend toward significance with FI-T. Clinically meaningful improvements (MCID >4-5 points) across all HRQoL scales were experienced by maralixibat responders. The placebo group showed no significant differences between pruritus responders and non-responders in any of the assessments. These data suggest that benefits of maralixibat may extend beyond pruritus and yield meaningful improvements in quality of life as well. Poster 4604-C: Maralixibat leads to significant improvement in cholestatic pruritus for children with progressive familial intrahepatic cholestasis due to TJP2 or MYO5B deficiency: Data from the MARCH-PFIC trial The MARCH study assessed the broadest set of genetic types associated with PFIC. The most common causes of PFIC are deficiencies in BSEP (PFIC2), FIC 1, MDR3, TJP2, and MYO5B. Patients with TJP2 deficiency have a predisposition to developing hepatocellular carcinoma. The goal of this analysis was to understand maralixibat’s potential to provide improvement across key markers of the disease in patients with these two rare genetic variants (TJP2, n=7, MYO5B, n=4). The results demonstrated that all patients with either a TJP2 or MYO5B deficiency receiving maralixibat achieved substantial improvements in pruritus and reductions in sBA while patients who received placebo experienced little benefit. Bilirubin levels were normalized in one participant with MYO5B deficiency who received maralixibat. MARCH is the first trial demonstrating benefit of IBAT inhibition for TJP2 and MYO5B deficiencies and these data support the use of maralixibat in patients with these genetic types. Poster 4605-C: Maralixibat leads to significant improvements in cholestatic pruritus for children with progressive familial intrahepatic cholestasis without a genetic diagnosis: Data from the MARCH-PFIC trial The MARCH study evaluated patients (n=8) with a PFIC clinical diagnosis without an identified genetic variant. The objective of this analysis was to understand the efficacy and safety of maralixibat treatment for patients clinically diagnosed with PFIC but without a known genetic variant. Data demonstrated that maralixibat was associated with improvements in pruritus, sBA levels, total bilirubin, and direct bilirubin, as compared to placebo. No new safety signals were observed. These data demonstrate the utility of treating patients with PFIC but without a known genetic variant with maralixibat. Poster 4547-C: Efficacy, safety and tolerability of volixibat in patients with intrahepatic cholestasis of pregnancy: A case series of 4 patients Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic liver disease impacting pregnant woman. ICP is characterized by elevated sBA and cholestatic pruritus, often impairing sleep and quality of life. Elevated sBAs pose significant risk to the unborn fetus. A Phase 2 open-label study, OHANA, was conducted with volixibat, a minimally absorbed IBAT inhibitor, to evaluate the efficacy and safety in four patients with ICP. Volixibat demonstrated improvements in pruritus and sBA levels, signaling proof of concept for volixibat in cholestatic disease. No clinically meaningful changes in liver enzyme levels or hematology parameters were observed after volixibat treatment. The most common TEAEs were GI in nature, transient and moderate in severity. About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older. LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com. Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older, and in Europe, in PFIC for patients two months of age and older. LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS, PFIC and biliary atresia. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website. IMPORTANT SAFETY INFORMATION LIVMARLI can cause side effects, including: Changes in liver tests. Changes in certain liver tests are common in patients with Alagille syndrome and can worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your healthcare provider should do blood tests before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen) or loss of appetite. Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you. A condition called Fat Soluble Vitamin (FSV) Deficiency is caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment. Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures. US Prescribing Information EU SmPC Canadian Product Monograph About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, Cholbam® (cholic acid) capsules, and Chenodal® (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in Canada. Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older and in Europe in PFIC for patients two months of age and older. Cholbam is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme defects and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. Chenodal has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX). Mirum’s late-stage pipeline includes three investigational treatments for debilitating liver diseases. The LIVMARLI development program includes the Phase 2b EMBARK study for biliary atresia. Mirum’s second investigational IBAT inhibitor is volixibat, which is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, Chenodal, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter. Forward-Looking Statements This press release includes forward-looking statements pertaining to the Company’s planned participation at a scientific conference, including data presentation title and synopsis, which may include discussion of the Company’s clinical and research data, including the therapeutic potential and/or commercial viability of our products and product candidates in various liver disease indications. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The accuracy of such statements is subject to a number of risks, uncertainties and assumptions including, but are not limited to, the following factors: the uncertainties inherent in research and development; the uncertainties inherent in business and financial planning, including, without limitation, risks related to Mirum’s business and prospects, adverse developments in our focused markets, or adverse developments in the U.S. or global regulatory environment or economies generally; the continued impact of COVID-19 on our business, operations and financial results; and competitive developments. Other factors that might cause such a difference include those discussed in the Company’s filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Abbreviations: PedsQL-SF – Social functioning PedsQL-PF – Physical functioning FI-T – Family Impact Total Scale HRQoL – Health Related Quality of Life View source version on businesswire.com: Contacts Media: Erin Murphy 510-508-6521 media@mirumpharma.com Investors: Andrew McKibben ir@mirumpharma.com Sam Martin Argot Partners ir@mirumpharma.com Source: Mirum Pharmaceuticals, Inc. View this news release online at:

- Late-breaker poster presentation accepted featuring LIVMARLI® data showing long-term maintenance of response in patients with PFIC - Four poster presentations will highlight LIVMARLI PFIC data and volixibat proof-of-concept trial data in intrahepatic cholestasis of pregnancy FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced that data from its LIVMARLI and volixibat programs will be presented at The Liver Meeting®, the American Association for the Study of Liver Diseases (AASLD) annual meeting, taking place November 10-14, 2023, in Boston, Massachusetts. Presentations during AASLD Late-breaker Poster Presentation November 13, 2023 from 1:00-2:00 p.m. as part of the late-breaker poster presentation session Poster Number 5048-C: Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study Poster Presentations Presented November 13, 2023 from 1:00-2:00 p.m. Poster 4602-C: Improvements in pruritus with maralixibat are associated with improved quality of life for patients with progressive familial intrahepatic cholestasis: Data from the MARCH-PFIC trial Poster 4604-C: Maralixibat leads to significant improvement in cholestatic pruritus for children with progressive familial intrahepatic cholestasis due to TJP2 or MYO5B deficiency: Data from the MARCH-PFIC trial Poster 4605-C: Maralixibat leads to significant improvements in cholestatic pruritus for children with progressive familial intrahepatic cholestasis without a genetic diagnosis: Data from the MARCH-PFIC trial Poster 4547-C: Efficacy, safety and tolerability of volixibat in patients with intrahepatic cholestasis of pregnancy: A case series of 4 patients Full data will be available within the Publications and Presentations section on Mirum’s website on November 13. About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older. LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com. Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older, and in Europe, in PFIC for patients two months of age and older. LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS, PFIC and biliary atresia. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website. IMPORTANT SAFETY INFORMATION LIVMARLI can cause side effects, including: Changes in liver tests. Changes in certain liver tests are common in patients with Alagille syndrome and can worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your healthcare provider should do blood tests before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen) or loss of appetite. Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you. A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment. Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures. US Prescribing Information EU SmPC Canadian Product Monograph About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, Cholbam® (cholic acid) capsules, and Chenodal® (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in Canada. Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older and in Europe in PFIC for patients two months of age and older. Cholbam is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme defects and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. Chenodal has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX). Mirum’s late-stage pipeline includes three investigational treatments for debilitating liver diseases. The LIVMARLI development program includes the Phase 2b EMBARK study for biliary atresia. Mirum’s second investigational IBAT inhibitor is volixibat, which is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, Chenodal, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter. Forward-Looking Statements This press release includes forward-looking statements pertaining to the Company’s planned participation at a scientific conference, including data presentation title and synopsis, which may include discussion of the Company’s clinical and research data, including the therapeutic potential and/or commercial viability of our product candidates and technologies in various liver disease indications. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The accuracy of such statements is subject to a number of risks, uncertainties and assumptions including, but are not limited to, the following factors: the uncertainties inherent in research and development; the uncertainties inherent in business and financial planning, including, without limitation, risks related to Mirum’s business and prospects, adverse developments in our focused markets, or adverse developments in the U.S. or global regulatory environment or economies generally; the continued impact of COVID-19 on our business, operations and financial results; and competitive developments. Other factors that might cause such a difference include those discussed in the Company’s filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Seven abstracts to be presented demonstrating treatment effects of Bylvay® in two cholestatic liver diseases, progressive familial intrahepatic cholestasis and Alagille syndrome Data to be presented from a qualitative trial on patient validation of pruritus (itch) and fatigue assessment tools for people living with primary biliary cholangitis (PBC), used as part of the ELATIVE Phase III registrational trial for elafibranor PARIS, FRANCE, 12 June 2023 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the company will present data from across its growing rare liver disease portfolio, at the European Association for the Trial of Liver (EASL) Congress 2023, 21-24 June in Vienna, Austria. These include seven abstracts on new clinical data being presented on Bylvay® (odevixibat) when used in patients with progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS). In addition, an abstract on content validation of patient-reported outcomes assessment tools, used with patients with primary biliary cholangitis (PBC), is being presented. The Bylvay abstracts provide further understanding of the treatment’s efficacy and safety profile, when used in sub-groups of both paediatric and adult patients with PFIC. The data report on outcomes including event free survival, reduction in serum bile acids (sBAs), pruritus and other quality of life outcomes, in long-term clinical trial and real-world settings. In the investigational Bylvay indication for patients with ALGS, new pooled data from the Phase III ASSERT trial and extension studies demonstrate significant improvements in pruritus and sBAs and sleep disturbances. The patient-reported outcomes assessment tools, include the PBC Worst Itch Numeric Rating Scale (PBC WI NRS) and PROMIS Fatigue Short Form 7a (PFSF 7a), are being used to assess symptoms in ELATIVE, a Phase III clinical trial of elafibranor, an investigational therapy for PBC. The tools have been designed to derive meaningful change thresholds among patients with PBC experiencing symptoms like pruritus (itch) and fatigue. PBC is a disease where symptoms can be debilitating for patients and have a significant impact on their quality of life.1, 2 Finally, two abstracts will be presented on pre-clinical data from two pipeline assets under investigation for further cholestatic diseases. “We look forward to presenting additional data from our Phase III Bylvay trials in both PFIC and ALGS, in addition to data supporting the validation of the patient report outcome tools we are using in our Phase III trial ELATIVE, with investigational elafibranor, amongst the scientific peer group attending EASL 2023,” said Dr. Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen. “These data highlight our ongoing focus on supporting the communities of patients living with rare liver disease by better understanding their needs and furthering research on potential treatment options.” Highlights from key data to be presented during the EASL congress 2023 include: Analysis of long-term treatment effects of Bylvay in children with PFIC compared to matched, non-Bylvay treated patients from the NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED) registry. Outcomes from a case trial focused on the treatment of Bylvay in patients with PFIC with the MYO5B mutation. Discoveries from a subgroup in the PEDFIC 2 trial, showing Bylvay’s efficacy and tolerability in adults with PFIC. A real-world case series demonstrating Bylvay’s effectiveness and safety in adults with genetic cholestasis disorders. Pooled data from ASSERT Phase III and ASSERT-EXT studies, showing efficacy and safety outcomes after 36-weeks of treatment. Insights from AS03969 and A3907, early stage ASBT inhibitors, in development for adult liver diseases. Trial results on the relevance and importance of the Primary Biliary Cholangitis Worst Itch Numerical Rating Scale (PBC WI NRS) and PROMIS Fatigue Short Form 7a (PFSF 7a), two clinical outcome assessment tools for symptomatic patients living with PBC. +++ Full presentation details: Poster (Abstract #1511): Analysis of long-term treatment effects of odevixibat on clinical outcomes in children with progressive familial intrahepatic cholestasis in odevixibat clinical studies vs external controls from the NAPPED database.Presenter: Bettina Hansen, Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands; Toronto Centre for Liver Disease & TGHRI, University Health Network, Canada; IHPME, University of Toronto, Toronto, CanadaSession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #912): Efficacy and safety outcomes with odevixibat treatment: Pooled data from the Phase 3 ASSERT and ASSERT-EXT studies in patients with Alagille syndrome Session title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #1031): Outcomes in adult patients with progressive familial intrahepatic cholestasis treated with odevixibat: subgroup analysis from the PEDFIC 2 trialPresenter: Henkjan Verkade, Department of Paediatrics, University of Groningen, Beatrix Children’s Hospital/University Medical Centre Groningen, Groningen, the NetherlandsSession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #1039): Real-world experience of odevixibat in adults with genetic disorders of cholestasis Presenter: Palak Trivedi, National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UKSession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #1013): Long-term efficacy and safety of odevixibat in patients with progressive familial intrahepatic cholestasis: results with 96 weeks or more of treatmentPresenter: Ekkehard Sturm, Paediatric Gastroenterology and Hepatology, University Children’s Hospital Tübingen, Tübingen, GermanySession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #1017): Odevixibat therapy following liver transplantation in patients with FIC1-deficient progressive familial intrahepatic cholestasis: a retrospective case seriesPresenter: Georg-Friedrich Vogel, Department of Paediatrics I, Medical University of Innsbruck, Innsbruck, Austria; Institute of Cell Biology, Medical University of Innsbruck, Innsbruck, AustriaSession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract #1323): Odevixibat therapy in patients with MYO5B mutations: a retrospective case seriesPresenter: Emmanuel Gonzalès, Hépatologie et Transplantation Hépatique Pédiatriques, Hôpital Bicêtre, Paris, FranceSession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Poster (Abstract 1067): Evaluating pruritus and fatigue in patients with treatment-refractory primary biliary cholangitisPresenters: Peter Serafini, Director Global Market Access and Marwan Sleiman, Global Medical Affairs Director, Ipsen Session title: Rare liver diseases (including paediatric and genetic)Date and time: 22nd June, 09:00-18:00 CEST Poster (Abstract #1325): Inhibition of the renal apical sodium-dependent bile acid transporter prevents cholemic nephropathyPresenter: Ahmed Ghallab, Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystr 67, 44139, Dortmund, GermanySession title: Poster - Rare liver diseasesDate and time: June 22, 2023 | 9:00-18:30 Oral (ID OS-074-YI): A3907, a systemic ASBT inhibitor, improves cholestasis in mice by inhibiting multi-organ bile acid transport and shows translational relevance to humansPresenter: Francisco J. Caballero-Camino, Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, SpainSession title: Immune-mediated and cholestatic diseasesDate and time: June 24, 2023 | 15-15:15 Follow Ipsen on Twitter via @IpsenGroup and keep up to date with EASL news and updates by using the hashtag #EASLCongress ENDS About the Phase III PEDFIC studiesThe PEDFIC trials represent the largest studies ever completed in children with PFIC, or progressive familial intrahepatic cholestasis, a rare genetic disorder that causes progressive, life-threatening liver disease. PEDFIC 1 was a randomized, double-blind, placebo-controlled Phase III trial that evaluated the efficacy and tolerability of Bylvay in reducing pruritus and serum bile acids (sBAs) in children with PFIC, and PEDFIC 2 is a long-term, open-label Phase III extension trial. Patients with PFIC have impaired bile flow, or cholestasis, and the resulting bile build-up in liver cells causes liver disease and symptoms, such as intense itching, poor sleep, delayed growth, and diminished quality of life. The harmful impacts of the disease extend to parents and caregivers, as the 2022 multinational PICTURE trial revealed that PFIC negatively affects caregivers’ quality of life, relationships, and career prospects. About the Phase III ASSERT trialASSERT is a gold standard, prospective intervention trial with 32 sites across North America, Europe, Middle East, and Asia Pacific. The double-blind, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy of 120 µg /kg/day Bylvay for 24 weeks in relieving pruritus in patients with ALGS. Key secondary endpoints measure serum bile acid levels and safety and tolerability. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS. In the primary analysis, the trial met the primary endpoint showing statistically significant reduction in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), compared to the placebo arm (p=0.002). Over 90% of patients were pruritus responders during the trial, as defined as at least a 1-point drop at any time point. The trial also met the key secondary endpoint showing a statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24 (compared to the placebo arm p=0.001). Statistically significant improvements in multiple sleep parameters were observed as early as week 1-4 compared to patients on placebo with continued improvement through week 24. In the trial, there were no patient discontinuations. Bylvay was well tolerated, with an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo). About Bylvay® (odevixibat)Bylvay is a potent, once-daily, non-systemic IBATi that acts locally in the small intestine and has minimal systemic exposure. It is approved in the U.S. for the treatment of pruritus in patients three months of age and older with PFIC, where it has orphan exclusivity. Bylvay was first launched as a treatment option for patients with PFIC in the U.S. in 2021, where it is supported by a program designed to assist with access to treatment and patient support. Bylvay is also approved in the E.U. for the treatment of PFIC in patients aged six months or older. It has launched in over nine countries and has secured public reimbursement across several major markets including Germany, Italy, the U.K., France and Belgium. View full E.U. prescribing information here: Bylvay, INN-odevixibat (europa.eu)View full U.S. prescribing information here: label (fda.gov) About the PBC trial: Evaluating pruritus and fatigue in patients with treatment-refractory primary biliary cholangitisSemi-structured qualitative interviews were conducted with 20 patients (aged 28-68 years; 19 females) diagnosed with PBC, (mean 10.7 years since diagnosis) experiencing pruritus (mild [30%], moderate [45%] or severe [25%]), using Institutional Review Board-approved materials. The PFSF 7a consists of 7 items that measure both the experience of fatigue and interference of fatigue on daily activities over the past 7 days using a Likert response scale. Patients were asked to evaluate the PBC WI NRS and PFSF 7a on ease of understanding of instructions and items, ease of use of scale/response options, and appropriateness of recall period to capture the patient experience. Interviews were conducted by experienced qualitative researchers, and audio recordings were transcribed and analyzed with coding software. About ElafibranorElafibranor is a novel, oral, once-daily, dual peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist, currently under investigation as treatment for patients with PBC, a rare liver disease. In 2019, it was granted a Breakthrough Therapy designation by the FDA in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA). Elafibranor has not received approval by regulatory authorities anywhere in the world. About Ipsen Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With total sales of €3.0bn in FY 2022, Ipsen sells medicines in over 100 countries. Alongside its external-innovation strategy, the Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has around 5,400 colleagues worldwide and is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com References: Mells GF et al. Hepatology. 2013 ; 58 : 273-283Poupon RE et al. Hepatology. 2004 ; 40(2) : 489-494 For further information: Ipsen Contacts Investors Craig MarksVice President, Investor Relations+44 (0)7584 349 193 Media Anna GibbinsGlobal Head of Franchise Communications,Rare Disease+44 (0)7717801900 Amy WolfVP, Head of Corporate Brand Strategy & Communications+41 79 576 07 23 Ioana PiscociuSenior ManagerGlobal Media Relations+33 6 69 09 12 96 Ipsen’s forward-looking statementsThe forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com. Attachment Ipsen PR_EASL_2023_12062023