Cholestasis, Progressive Familial Intrahepatic 2

Early, rapid, and sustained efficacy across wide range of patients with evidence of disease modificationLong-term preservation of native liver in PFIC, improvements in pruritus, bile acids, and increased growth over timeLate-breaking oral presentation demonstrates restoration of bile acid secretion in PFIC patients receives “Best of Liver Meeting” distinctionLate-breaking oral presentation of new positive Phase 3 ASSERT trial results in Alagille syndrome receives “Best of Liver Meeting” distinction BOSTON, Nov. 07, 2022 (GLOBE NEWSWIRE) -- Albireo Pharma, Inc. (Nasdaq: ALBO), a rare disease company developing novel bile acid modulators to treat pediatric and adult liver diseases, presented new data at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® 2022, being held November 4 – 8, 2022 in Washington, D.C. Across three oral presentations, including two late-breakers, and six posters, the Company provided evidence of early, rapid, and sustained efficacy with Bylvay (odevixibat) treatment in patients with progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS). Two key oral presentations on the PEDFIC trials provided evidence of the disease modifying effects of Bylvay in patients with PFIC. The first underscored that a decrease in serum bile acids was strongly associated with native liver survival for up to three years in PFIC patients treated with Bylvay. A second late-breaking oral presentation showed that Bylvay restored bile acid secretion in PFIC patients with bile salt export pump deficiency. The late-breaking abstract was selected by AASLD for inclusion as a key presentation in “The Best of The Liver Meeting” in the Pediatric Hepatology category. “We are pleased to share long term data in PFIC, providing evidence that Bylvay could modify the course of disease, preserving patients’ native liver and improving families’ quality of life by alleviating disease burden,” said Jan Mattsson, Ph.D., Chief Scientific Officer and Head of R&D at Albireo. “Furthermore, showing early, rapid, and consistent improvements in pruritus and bile acid levels in patients with Alagille syndrome, through the ASSERT body of evidence, makes for a big year at this year’s AASLD congress. PFIC and Alagille syndrome are devastating childhood diseases and our goal at Albireo has always been to relieve the suffering of these young patients and their families.” “Patients with PFIC have long needed a disease modifying treatment,” said Dr. Richard Thompson, Professor of Molecular Hepatology at King’s College London, and principal investigator of the PEDFIC 1 and PEDFIC 2 trials. “Sadly, most children with PFIC end up having a liver transplant, with fewer than half of PFIC1 patients and less than a third of PFIC2 patients keeping their native liver through their eighteenth birthday. I am encouraged by long-term data that showed Bylvay reduced serum bile acids after six months, and helped patients preserve their native liver. This supports the importance of treating early with Bylvay so children can benefit from the protective effects we are seeing on the liver.” Along with results observed with Bylvay treatment in PFIC patients, Albireo shared the first detailed results of the Phase 3 ASSERT trial in Alagille syndrome (ALGS) in a late-breaking oral presentation. The data showed that Bylvay provided early, rapid, clinically meaningful, and sustained improvements in pruritus, as well as significant reductions in bile acids and improvements in sleep quality in patients with ALGS. The ASSERT abstract was selected by AASLD for inclusion as a key presentation in “The Best of The Liver Meeting” in the Pediatric Hepatology category. Analyses of the ASSERT and PEDFIC trials and real-world data on Bylvay treatment, as well as data on the investigational therapy A3907, were highlighted in the following presentations at AASLD The Liver Meeting: Early, Rapid, Sustained Effects in Alagille Syndrome Oral, Late-Breaking Parallel Session Presentation (Abstract #5005; Publication #38786): Efficacy and Safety of Odevixibat in Patients with Alagille Syndrome: Top-Line Results from ASSERT, a Phase 3, Double-Blind, Randomized, Placebo-Controlled StudyPresenter: Dr. Nadia Ovchinsky, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USASession: Late-Breaking Oral Abstract Session 1; Monday, November 7, 2022, 9:15 AM EST Top-line, unblinded data from the ASSERT study demonstrated that Bylvay treatment led to significant and clinically meaningful improvements in pruritus, as well as reductions in bile acid levels and improvements in sleep parameters in patients with ALGS​. Over 90% of patients were pruritus responders and the treatment effects were early, rapid, and sustained. ​Bylvay was generally well tolerated; the overall incidence of treatment emergent adverse events (TEAEs) was similar to placebo​. No patients discontinued the study​ and 96% of patients rolled over into the open-label extension study​. Disease Modification in PFIC Oral Presentation (Abstract #865): Native Liver Survival in Odevixibat Serum Bile Acid Responders: Data from the PEDFIC Studies in Patients with Progressive Familial Intrahepatic CholestasisPresenter: Dr. Richard J. Thompson, Institute of Liver Studies, King’s College LondonSession: Genes to Cures: What’s New in Pediatric Liver Disease; Sunday, November 6, 2:10 PM EST Pooled data analysis showed that PFIC patients who responded to Bylvay remained liver transplant free for up to three years. A decrease in serum bile acids (sBAs) at six months of treatment was strongly associated with native liver survival (p=0.0050) for sBA responders vs non-responders. Oral, Late-Breaking Parallel Session Presentation (Abstract #5004; Publication #38801): Odevixibat Treatment in Responsive Patients with Bile Salt Export Pump Deficiency Restores Biliary Bile Acid Secretion, as Indicated by Serum Bile Acid CompositionPresenter: Dr. Mark Nomden, Department of Surgery and Pediatrics, University Medical Center Groningen, Groningen, the NetherlandsSession: Late-Breaking Oral Abstract Session 1; Monday, November 7, 2022, 10:00 AM EST The analysis found that responders not only had a decrease in sBA concentration, but also alternations in sBA composition, more like that of a healthy individual. Data indicated that Bylvay restored biliary bile acid secretion in treatment-responsive patients with BSEP deficiency. Durable Improvement Across Wide Range of PFIC Patients Poster (Abstract #37939): Long-term Efficacy and Safety of Odevixibat in Patients with Progressive Familial Intrahepatic Cholestasis: Results with 96 Weeks or More of TreatmentPresenter: Dr. Richard J. Thompson, Institute of Liver Studies, King’s College LondonSession: Poster Session IV; Monday, November 7, 1:00 PM – 2:00 PM EST Pooled data analysis showed Bylvay treatment for 96 weeks or more was associated with durable clinical benefits in patients with PFIC, with improvements over time in mean sBA and aminotransferase levels and growth. Mean levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased over time, while mean total bilirubin levels were relatively unchanged. Mean height and weight Z scores also increased over time and Bylvay was generally well tolerated. Poster (Abstract #37254): Serum Bile Acid Levels, Pruritus Scores, and Growth Over Time in Odevixibat Responders: Pooled Data from the PEDFIC Studies in Patients with Progressive Familial Intrahepatic CholestasisPresenter: Dr. Lorenzo D'Antiga, Department of Paediatric Hepatology, Gastroenterology, and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, ItalySession: Poster Session IV; Monday, November 7, 1:00 PM – 2:00 PM EST This analysis of pooled data examined treatment effects in 49 Bylvay responders who had a mean duration of exposure of 110 weeks and showed mean reductions in sBAs and pruritus were sustained over time, across PFIC types in general. Patients also had mean improvements in growth. Poster (Abstract #37273): Effect of Odevixibat in Patients with Progressive Familial Intrahepatic Cholestasis Type 2 with at Least 1 Severe Mutation (BSEP3 Compound Heterozygotes): Pooled Data from the PEDFIC 1 and PEDFIC 2 StudiesPresenter: Dr. Henkjan J. Verkade, Department of Paediatrics, University of Groningen, Beatrix Children’s Hospital/University Medical Centre Groningen, Groningen, the NetherlandsSession: Poster Session IV; Monday, November 7, 1:00 PM – 2:00 PM EST Partial external biliary diversion (PEBD) is not effective in PFIC2 patients with BSEP 3 mutations, but this pooled data analysis showed that treatment with Bylvay provided substantial reductions in sBAs and/or pruritus severity in most patients with BSEP2/BSEP3 mutations, demonstrating that Bylvay may provide an alternative to surgical intervention for these patients. Poster (Abstract #37608): Odevixibat Therapy in Patients with FIC1-Deficient Progressive Familial Intrahepatic Cholestasis and Diarrhea Following Liver Transplantation That Impacted Daily Activities: A Retrospective Case SeriesPresenter: Georg-Friedrich Vogel, Assistant Professor, Medical University of Innsbruck, Innsbruck, AustriaSession: Poster Session IV; Monday, November 7, 1:00 PM – 2:00 PM EST Chologenic diarrhea can be a frequent and severe symptom after liver transplant in patients with FIC1 deficiency. Real-world data in three PFIC1 patients indicated that treatment with Bylvay can improve diarrhea and quality of life in PFIC1 patients with severe diarrhea after transplant. Poster (Abstract #850): Odevixibat Treatment in Patients with Recurrent Episodic Cholestasis and Biallelic Mutations in ATP8B1: A Retrospective Case SeriesPresenter: Dr. Angelo Di Giorgio, Hospital Papa Giovanni XXIII, Bergamo, ItalySession: Poster Session IV; Monday, November 7, 1:00 PM – 2:00 PM EST Recurrent episodic cholestasis is a rare disease characterized by episodes of cholestasis followed by periods of remission. In a case series of six patients treated with Bylvay during a cholestasis episode, most patients experienced clinical improvement, including improvements in sBA levels, hepatic laboratory parameters, pruritus, sleep disturbances and impacts on daily life. Before starting Bylvay treatment, all 6 patients had high sBAs and severe pruritus leading to sleep or mood disturbances and/or the inability to attend school, play sports or work. ASBTi A3907 for Cholestatic Liver Diseases The apical sodium-dependent bile acid transporter (ASBT) plays an important role in regulation of bile acid homeostasis by promoting the reuptake of bile acids in the ileum, bile ducts, and proximal tubuli of the kidney. A3907 is an investigational therapy that is designed to inhibit ASBT to potentially benefit people with cholestatic liver diseases. The study showed that A3097 improved the general condition and liver phenotype of mice with induced obstructive cholestasis by promoting urinary secretion of bile acids, demonstrating that A3907 may have therapeutic potential for patients with cholestatic liver diseases. Treatment with A3907 resulted in marked decreases in serum and bile levels of bile acids relative to vehicle. The A3907 study was selected among the four posters for the Cholestatic and Autoimmune Liver Diseases SIG (Special Interest Group) debrief. Poster (Abstract #37733): Systemic ASBT Inhibition with A3907 Stimulates Urinary Excretion of Bile Acids and Halts Liver Disease Progression in Bile-Duct–Obstructed MicePresenters: Drs. Peter Åkerblad and Erik Lindström, Albireo, Boston, MA, USASession: Poster Session III; Sunday, November 6, 1:00 PM – 2:00 PM EST About the Phase 3 PEDFIC & ASSERT Studies The 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 3 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 3 extension study. 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 study revealed that PFIC negatively affects caregivers’ quality of life, relationships, and career prospects. ASSERT is a gold standard, prospective intervention trial in Alagille syndrome, or ALGS, a rare, multisystem genetic disorder that can affect the liver, heart, skeleton, eyes, central nervous system, kidneys, and facial features. With 32 sites across North America, Europe, Middle East, and Asia Pacific, the double-blind, randomized, placebo-controlled ASSERT trial was designed to evaluate the safety and efficacy of 120 µg /kg/day Bylvay for 24 weeks in relieving pruritus in patients with Alagille syndrome (ALGS). Key secondary endpoints measure serum bile acid levels, safety, and tolerability. The Company estimates that ALGS impacts 25,000 people globally. In people with ALGS, liver damage is caused by a paucity of bile ducts preventing bile flow from the liver to the small intestine. Approximately 95% of patients with the condition present with chronic cholestasis, usually within the first three months of life, and as many as 88 percent also present with severe, intractable pruritus. About Bylvay (odevixibat)Bylvay is the first drug approved in the U.S. for the treatment of pruritus in patients 3 months of age and older in all types of progressive familial intrahepatic cholestasis (PFIC). Limitation of Use: Bylvay may not be effective in PFIC type 2 patients with ABCB11 variants resulting in non-functional or complete absence of bile salt export pump protein (BSEP-3). The European Commission (EC) and UK Medicines and Healthcare products Regulatory Agency (MHRA) have also granted marketing authorization of Bylvay for the treatment of PFIC in patients aged 6 months or older. A potent, once-daily, non-systemic ileal bile acid transport inhibitor, Bylvay has minimal systemic exposure and acts locally in the small intestine. Bylvay can be taken as a capsule for patients that are able to swallow capsules, or opened and sprinkled onto food, which is a factor of key importance for adherence in a pediatric patient population. The most common adverse reactions for Bylvay are diarrhea, liver test abnormalities, vomiting, abdominal pain, and fat-soluble vitamin deficiency. The medicine can only be obtained with a prescription. For more information about using Bylvay, see the package leaflet or contact your doctor or pharmacist. For full prescribing information, visit www.bylvay.com. In the U.S. and Europe, Bylvay has orphan exclusivity for its approved PFIC indications, and orphan designations for the treatment of ALGS, biliary atresia and primary biliary cholangitis. Bylvay is being evaluated in the ongoing PEDFIC 2 open-label trial in patients with PFIC, in the BOLD Phase 3 study for patients with biliary atresia and the ASSERT open-label trial for ALGS.Important Safety Information The most common adverse reactions for Bylvay are diarrhea, liver test abnormalities, vomiting, abdominal pain, and fat-soluble vitamin deficiency.Liver Test Abnormalities: Patients should obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required if abnormalities occur. For persistent or recurrent liver test abnormalities, consider treatment discontinuation.Diarrhea: Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea.Fat-Soluble Vitamin (FSV) Deficiency: Patient should obtain baseline vitamin levels and monitor during treatment. Supplement if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, discontinue treatment. About AlbireoAlbireo Pharma is a rare disease company focused on the development of novel bile acid modulators to treat pediatric and adult liver diseases. Albireo’s lead product, Bylvay, was approved by the U.S. FDA as the first drug for the treatment of pruritus in all types of progressive familial intrahepatic cholestasis (PFIC), and it is also being developed to treat other rare pediatric cholestatic liver diseases with a completed Phase 3 trial in Alagille syndrome (ALGS), an ongoing Phase 3 study in biliary atresia, as well as Open-label Extension (OLE) studies for PFIC and ALGS. In Europe, Bylvay is reimbursed for the treatment of PFIC in Germany, England, Wales & Northern Ireland, Scotland, Italy, and Belgium. The Company has also completed a Phase 1 clinical trial for A3907 to advance development in adult cholestatic liver disease, with IND-enabling studies progressing with A2342 for viral and cholestatic liver disease. Albireo was spun out from AstraZeneca in 2008 and is headquartered in Boston, Massachusetts, with its key operating subsidiary in Gothenburg, Sweden. For more information on Albireo, please visit www.albireopharma.com. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements, other than statements of historical fact, regarding, among other things: Albireo’s expected cash runway; Albireo’s commercialization plans; the plans for, or progress, scope, cost, initiation, duration, enrollment, results or timing for availability of results of, development of Bylvay, A3907, A2342 or any other Albireo product candidate or program; the target indication(s) for development or approval; ;discussions with the FDA or EMA regarding our programs; potential regulatory approval and plans for potential commercialization of Bylvay in biliary atresia or ALGS or Albireo’s other product candidates; the potential benefits or competitive position of Bylvay or any other Albireo product candidate or program or the commercial opportunity in any target indication; or Albireo’s plans, expectations or future operations, financial position, revenues, costs or expenses. Albireo often uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “planned,” “continue,” “guidance,” or the negative of these terms or other similar expressions to identify forward-looking statements. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to: whether the regulatory filings to be made for Bylvay in patients with ALGS will be made on the timelines we expect and be approved by the FDA and EMA; whether the FDA and EMA will complete their respective reviews within target timelines, once determined; whether the FDA and EMA will require additional information, whether we will be able to provide in a timely manner any additional information that the FDA and EMA request, and whether such additional information will be satisfactory to the FDA and EMA; there are no guarantees that Bylvay will be commercially successful; we may encounter issues, delays or other challenges in commercializing Bylvay; whether Bylvay receives adequate reimbursement from third-party payors; the degree to which Bylvay receives acceptance from patients and physicians for its approved indication; challenges associated with execution of our sales activities, which in each case could limit the potential of our product; challenges associated with supply and distribution activities, which in each case could limit our sales and the availability of our product; results achieved in Bylvay in the treatment of patients with PFIC or other approved indications may be different than observed in clinical trials, and may vary among patients; potential negative impacts of the COVID-19 pandemic, including on manufacturing, supply, conduct or initiation of clinical trials, or other aspects of our business; whether favorable findings from clinical trials of Bylvay to date, including findings in PFIC, ALGS and other indications, will be predictive of results from other clinical trials of Bylvay; there is no guarantee that Bylvay will be approved in jurisdictions or for indications (such as biliary atresia or ALGS) beyond the jurisdictions in which or indications for which Bylvay is currently approved; there is no guarantee that our other product candidates will be approved; estimates of the addressable patient population for target indications may prove to be incorrect; the outcome and interpretation by regulatory authorities of the ongoing third-party study pooling and analyzing of long-term PFIC patient data; the timing for initiation or completion of, or for availability of data from, clinical trials of Bylvay, including BOLD, and the Phase 2 clinical trial of A3907, and the outcomes of such trials; Albireo’s ability to obtain coverage, pricing or reimbursement for approved products in the United States or Europe; delays or other challenges in the recruitment of patients for, or the conduct of, the Company’s clinical trials; and the Company’s critical accounting policies. These and other risks and uncertainties that Albireo faces are described in greater detail under the heading “Risk Factors” in Albireo’s most recent Annual Report on Form 10-K or in subsequent filings that it makes with the Securities and Exchange Commission. As a result of risks and uncertainties that Albireo faces, the results or events indicated by any forward-looking statement may not occur. Albireo cautions you not to place undue reliance on any forward-looking statement. In addition, any forward-looking statement in this press release represents Albireo’s views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Albireo disclaims any obligation to update any forward-looking statement except as required by applicable law. Media Contacts: Colleen Alabiso, 857-356-3905, colleen.alabiso@albireopharma.com Lance Buckley, 917-439-2241, lbuckley@lippetaylor.com Investor Contact: Hans Vitzthum, LifeSci Advisors, LLC., 617-430-7578

June 24, 2022 12:00 UTC - Six-year natural history comparison with maralixibat demonstrates event-free and transplant-free survival in patients with Alagille syndrome - Maralixibat data highlighting predictors of event-free survival in patients with Alagille syndrome nominated for prestigious Alex Mowat Prize - New analysis further characterizes 4-year growth improvement in Alagille syndrome, as well as reports on real world experience with LIVMARLI in ALGS patients with cholestatic pruritus FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) presented data from clinical programs evaluating maralixibat (LIVMARLI®) in patients with Alagille syndrome at the 54th Annual ESPGHAN Meeting. These data further characterize LIVMARLI’s clinical potential in pediatric patients including evaluation of its impact on long-term event-free survival. “We are thrilled for the opportunity to share key long-term findings from our clinical studies with the pediatric liver community during ESPGHAN,” said Dr. Pam Vig, head of research and development at Mirum. “The years of data that have been generated with maralixibat allow us to look critically at important long-term treatment goals such as growth, transplant rates and predictors of improved outcomes.” Summaries of data presented during the congress are enclosed below. View the presentations in full within our Publications & Presentations section on our website. H-O-018: Maralixibat-treated patients with ALGS demonstrate improved event-free survival in a natural history comparison with patients from the GALA database: Application of real-world evidence analytics Dr. Bettina Hansen on behalf of Dr. Binita Kamath and the GALA Study Group (Oral presentation) The presentation reported on an analysis independently conducted and presented by Dr. Bettina Hansen and the Global Alagille Alliance (GALA) Study Group, which has aggregated the largest global natural history clinical database established for ALGS. The analysis evaluated time to first clinical event using six years of follow-up data from pooled ALGS maralixibat studies (n=84) and compared it against an external natural history control cohort from the GALA clinical database. Events were defined as liver transplantation, biliary diversion surgery, decompensation events (ascites requiring therapy or variceal bleeding), or death. Additional analyses included transplant-free survival as well as several sensitivity and subgroup analyses to confirm robustness of the findings. The analysis demonstrated a highly significant improvement in six-year event-free survival with a p-value of <0.0001 (HR: 0.305, 95% CI: 0.189-0.491) translating to a 70% overall reduction for clinical outcomes with maralixibat. The analysis also showed highly statistically significant improvements in transplant-free survival with a p-value of <0.0001 (HR: 0.332, 95% CI: 0.197-0.559). View presentation H-O-012: Predictors of 6-year event-free survival in patients with ALGS treated with maralixibat, an IBAT inhibitor Dr. Ron Sokol (Oral Presentation) **Nominee for Alex Mowat Prize for Best Oral Presentation in Hepatology** Data from the pooled maralixibat clinical studies with up to six years of follow up were analyzed to determine predictors of event-free and transplant-free survival in patients with ALGS. 76 patients met the criteria for inclusion in this analysis and 43 variables were tested as predictors. The laboratory markers that were predictive of event-free and transplant-free survival included specific thresholds of week 48 total bilirubin and week 48 serum bile acids. In addition, improvement in pruritus from baseline to week 48 was also predictive of event-free and transplant-free survival. 76% and 79% of maralixibat-treated ALGS patients remained event-free and transplant-free, respectively, at six years after treatment initiation. These data highlighted potential prognostic markers that could help to inform medical management for patients receiving maralixibat. View presentation H-P-047: Significant improvement in cholestatic pruritus in patients with Alagille syndrome treated with maralixibat, an ileal bile acid transporter inhibitor: Real-world experience Dr. Regino Gonzalez-Peralta, Dr. Douglas Mogul (Poster presentation) The goal of this assessment was to evaluate the real-world application of maralixibat in children with ALGS and cholestatic pruritus. Three patients with ALGS were enrolled in the maralixibat Expanded Access Program with a variety of clinical manifestations. During the course of treatment with maralixibat, pruritus was assessed using the Clinician Scratch Scale (0-4 where 0=none and 4=cutaneous mutilation, hemorrhage and scarring was evident), and liver enzymes were monitored at varying time intervals in the months prior to and after starting maralixibat. The data showed that treatment with maralixibat led to significant and durable amelioration of pruritus in these individual children with ALGS. View presentation H-P-058: Maralixibat improves growth in patients with Alagille syndrome: A 4-year analysis Dr. Binita Kamath (Poster presentation) The analysis evaluated the impact of long-term maralixibat treatment on the growth and nutritional status of patients with ALGS, a disease for which patients typically present with significant growth deficits. Height and weight z-scores were evaluated in patients who participated in the maralixibat ICONIC study (along with the long-term, open label extension studies). The analysis included patients with ALGS who had both baseline and 204-week assessments for all eight parameters, and this group was divided into four subgroups based on height and weight z-score quartiles. No changes beyond standard of care in supplementation occurred during the study. The data showed that patients with ALGS treated with long-term maralixibat (up to four years) had significantly increased height from baseline to week 204 (p=0.0004). Patients with the lowest height and weight z-scores at baseline had the greatest improvements in height and weight z-scores, and individuals that had the greatest catch-up weight gain also had the greatest catch-up height growth at week 48 (p=0.0013). The analysis also concluded that maralixibat-treated patients who achieved an sBA threshold <200 µmol/L had greater accelerated height, suggesting bile acid homeostasis may facilitate improvement in height deficits. Further analyses, including comparison to natural history cohort of patients with ALGS are needed to fully characterize the impact of maralixibat treatment on growth. View presentation H-O-008: Maralixibat treatment response is associated with improved health-related quality of life in patients with bile salt export pump (BSEP) deficiency Dr. Doug Mogul on behalf of Dr. Kathy Loomes (Oral presentation) The analysis evaluated patients with BSEP deficiency, or PFIC2, following treatment with maralixibat. Patients with PFIC suffer from poor health-related quality of life (HRQoL) compared with healthy children, thus the aim of this analysis was to assess the impact of maralixibat treatment response at week 48 on HRQoL among a subset of children with BSEP deficiency from the INDIGO Phase 2 study. Overall, patients with BSEP deficiency who achieved sBA treatment response (defined as >75% decrease from baseline or reduction to <102 µmol/L from baseline to week 48) experienced clinically meaningful improvements in PedsQL Generic Core Total Scale Score and Multidimensional Fatigue Total Scale Score, as well as statistically significant improvements in sleep and fatigue, as compared to those who did not achieve an sBA response. Baseline characteristics were similar for responders and non-responders but baseline HRQoL Multidimensional Fatigue Score was lower for responders. With a minimal clinically important difference (MCID) of 4-5 points, the results demonstrated: PedsQL Generic Core Scale: responders improved significantly by >3× MCID (p=0.01) Multidimensional Fatigue Scale: responders improved significantly by >4× MCID (p=0.04) Family Impact Scale: clinically meaningful improvements did not reach statistical significance In conclusion, response to maralixibat has the potential to significantly improve HRQoL in patients with PFIC. View presentation H-P-057: Response to treatment with maralixibat in ALGS is associated with improved health-related quality of life Dr. Binita Kamath, et al (Poster presentation) The analysis evaluated 27 patients with ALGS who received 380 µg/kg per day of maralixibat and who remained in the ICONIC study through week 48, comparing their HRQoL outcomes as reported at baseline and at week 48. Treatment response to LIVMARLI was defined as a ≥1 point reduction in caregiver Itch-Reported Outcome Observer (ItchRO[Obs]) instrument score from baseline to week 48. In addition, the Pediatric Quality of Life (PedsQL™) questionnaires (Generic Core PedsQL, Family Impact Scale, and Multidimensional Fatigue Scale) were prospectively collected via a caregiver proxy report and analyzed retrospectively. At week 48, 20 patients (74%) met the definition of ItchRO(Obs) response. With a minimal clinically important difference (MCID) of 4-5 points, the results demonstrated: PedsQL Generic Core Scale: increased on average by 8.8 points, almost two times the minimal clinically important difference in responders. Responders improved >2× the MCID (increase of 8.8 points). Multidimensional Fatigue Scale: Responders improved increase of 13.9 points) >2× the MCID (increase of 13.9 points). Family Impact Scale: Responders improved by >3× the MCID (increase of 16.8 points). Six sleep-related items demonstrated significantly larger changes from baseline to week 48 in responders (p<0.05). These data demonstrate that the significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improvements in patients’ quality of life. View presentation About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) one year of age and older and is the only FDA-approved medication to treat cholestatic pruritus associated with Alagille syndrome. For more information, please visit LIVMARLI.com. LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including progressive familial intrahepatic cholestasis (PFIC) and 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 bone fractures and gastrointestinal bleeding. Prescribing information About Mirum Pharmaceuticals Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare liver diseases. Mirum’s approved medication is LIVMARLI® (maralixibat) oral solution which is approved in the U.S. for the treatment of cholestatic pruritus in patients with Alagille syndrome one year of age and older. Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases affecting children and adults. LIVMARLI, an oral ileal bile acid transporter (IBAT) inhibitor, is currently being evaluated in clinical trials for pediatric liver diseases and includes the MARCH Phase 3 clinical trial for progressive familial intrahepatic cholestasis (PFIC) and the EMBARK Phase 2b clinical trial for patients with biliary atresia. In addition, Mirum has an expanded access program open across multiple countries for eligible patients with ALGS and PFIC. Mirum has submitted a Marketing Authorization Application to the European Medicines Agency for LIVMARLI for the treatment of cholestatic liver disease in patients with Alagille syndrome. Mirum’s second investigational treatment, volixibat, an oral IBAT inhibitor, is being evaluated in three potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis, the OHANA Phase 2b clinical trial for pregnant women with intrahepatic cholestasis of pregnancy, and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis. Follow Mirum on Twitter, Facebook, LinkedIn and Instagram. 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 discovery, development and commercialization of our product candidates and technologies, and the therapeutic potential thereof, the continuation of our clinical trials, and the success of our collaborations with partners and any potential future collaborations. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Applicable risks and uncertainties include those relating to our preclinical research and clinical programs and other risks identified under the heading “Risk Factors” included in our most recent Form 10-Q and Form 10-K filings and in other future filings with the SEC. The forward-looking statements contained in this press release reflect Mirum's current views with respect to future events, and Mirum does not undertake and specifically disclaims any obligation to update any forward-looking statements, except as required by law.

Vivet Therapeutics AnnouncesMultiple Projects Update, IncludingNew VTX-803 Preclinical data To Be PresentedAt 2021 American Society Of Gene And Cell Therapy AnnualMeeting Compelling additional preclinical data further support therapeutic potential of gene therapy product to treat Progressive Familial IntrahepaticCholestasis Type 3 (PFIC3). Paris, France, May 10, 2021 – Vivet Therapeutics (“Vivet”), a clinical stage biotech company dedicated to developing gene therapy treatments for inherited liver disorders with high unmet medical need, today announced that new data regarding VTX-803, Vivet’s AAV-based gene therapy in development for the treatment of PFIC3, will be presented during the ASGCT 24th Annual Meeting, May 11 - 14, 2021. New findings from the recently completed preclinical studies of VTX-803 will be presented by Dr. Nicholas D. Weber, Research Scientist at Vivet. VTX-803 was already shown to normalize key serum biomarkers, hepatosplenomegaly and liver fibrosis in two-week-old (pre-fibrotic liver) or five-week-old (fibrotic liver) PFIC3 mice. Dr Weber will present new animal data expanding those results: “AAV-Based Gene Therapy for PFIC3 (VTX-803) Shows Further Promise with Durable Efficacy in PFIC3 Mice at Different Disease Stages” (Tuesday May 11, 2021; 8:00-10:00 AM EST – Abstract 503). These data show VTX-803 therapeutic effect in older animals (16 weeks) presenting severely fibrotic/cirrhotic livers, without an increase in dose. Dr. Weber will also present VTX-803 long-term studies showing the vector to be safe and the effect to be durable at least up to 6 months and comparable between 5-week-old and 16-week-old mice. Dr. Gloria González-Aseguinolaza, Vivet Therapeutics CSO and Deputy Director of Cima center of the Fundación para la Investigación Médica Aplicada (FIMA) will co-chair a session: “Gene Therapy for Inborn Errors of Metabolism” (Tuesday May 11, 2021; 5:30-7:30 PM EST), where Dr. Nick Weber will also be presenting additional data on VTX-803. Vivet is also developing an AAV-based gene therapy product, VTX-802 for Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2), currently at preclinical stage. Vivet and Mirum Pharmaceuticals recently announced an exclusive worldwide option, collaboration and license agreement for Vivet’s Gene Therapy programs targeting Progressive Familial Intrahepatic Cholestasis, VTX-802 and VTX-803. In addition, compelling data from a new animal proof of concept study for VTX-804, one of Vivet’s portfolio indications, an AAV-based gene therapy for Citrullinemia Type 1 (CTLN-1) will be presented by Andrea Bazo, PhD Student at Cima center-FIMA: “rAAV-Mediated Gene Therapy in Combination with Short-Term Nitrogen-Scavenger Treatment Corrects Biochemical and Behavioral Abnormalities and Increases Lifespan in Infant Citrullinemia Type 1 (CTLN-1) Mice” (Tuesday May 11, 2021; 8:00-10:00 AM EST – Abstract 520). CTLN-1 is a rare autosomal recessive urea cycle defect characterized biologically by hyperammonemia and clinically by progressive lethargy, poor feeding and vomiting in the neonatal form and by variable hyperammonemia in the later-onset form patients. These preclinical data show that a single dose of VTX-804 administered intravenously to infantile CTLN-1 mice in association with Standard of Care (SOC) normalized lifespan and corrected biochemical and behavioral abnormalities up to 6 months post administration, making VTX-804 a potentially very promising therapeutic strategy for young CTLN-1 patients. The abstracts listed above can be found online at: About Vivet Therapeutics Vivet Therapeutics is a clinical stage emerging biotechnology company developing novel gene therapy treatments for rare, inherited metabolic diseases. Vivet is building a diversified gene therapy pipeline based on novel recombinant adeno-associated virus (rAAV) technologies developed through its partnerships with, and exclusive licenses from, the Fundación para la Investigación Médica Aplicada (FIMA), a not-for-profit foundation at the Centro de Investigación Medica Aplicada (CIMA), University of Navarra based in Pamplona, Spain. Vivet’s lead program, VTX-801, currently under IND clinical development with the GATEWAY clinical trial, is a novel investigational gene therapy for Wilson disease which has been granted Orphan Drug Designation (ODD) by the Food and Drug Administration (FDA) and the European Commission (EC). This rare genetic disorder is caused by mutations in the gene encoding the ATP7B protein, which reduces the ability of the liver and other tissues to regulate copper levels causing severe hepatic damage, neurologic symptoms and potentially death. Vivet’s second gene therapy product, VTX-803 for PFIC3, received US and European Orphan Drug Designation in May 2020. Vivet is supported by international life science investors including Novartis Venture Fund, Roche Venture Fund, HealthCap, Pfizer Inc., Columbus Venture Partners, Ysios Capital, Kurma Partners and Idinvest Partners. Please visit us at and follow us on Twitter at @Vivet_tx and LinkedIn. About PFIC Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare genetic disorder that causes progressive liver disease typically leading to liver failure. In people with PFIC, liver cells are less able to secrete bile or essential components into the bile. The resulting dysregulation in the bile processing causes liver disease in affected individuals. Signs and symptoms of PFIC typically begin in infancy. Patients experience severe itching, jaundice, failure to grow at the expected rate (failure to thrive), and an increasing inability of the liver to function (liver failure). The disease is estimated to affect one in every 50,000 to 100,000 births in the United States and Europe. Six types of PFIC have been genetically identified, all of which are similarly characterized by impaired bile flow and progressive liver disease. The PFIC2 patient population accounts for approximately 60% of the PFIC patient population. PFIC2 is caused by a mutation in the ABCB11 gene, which normally encodes a bile salt export pump protein that moves bile acids out of the liver. PFIC3, is caused by a genetic defect in the ABCB4 gene (also designated MDR3) which encodes a phospholipid translocator involved in biliary phospholipid (phosphatidylcholine) excretion. In PFIC3, cholestasis results from the toxicity of bile in which detergent bile salts are not inactivated by phospholipids, leading to bile canaliculi and biliary epithelium injuries.