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.

加利福尼亚州福斯特城-（商业线）-Mirum Pharmaceuticals，Inc。（纳斯达克股票代码：MIRM）今天宣布了其LIVMARLI和volixibat计划的新数据，该计划在美国肝病研究协会肝脏会议®上发布（AASLD）年会在马萨诸塞州波士顿举行。

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)..

数据来自3月3日的研究和3月延长期，评估了LIVMARLI在进行性家族性肝内胆汁淤积症（PFIC）患者中的疗效和安全性，以及评估volixibat治疗妊娠期肝内胆汁淤积症（ICP）患者的疗效和安全性的2期OHANA研究。。

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.

MARCH是迄今为止最大，最具遗传多样性的PFIC试验，招募了BSEP，FIC1，MDR3，TJP2和MYO5B缺乏症的患者，以及临床诊断为PFIC但无已知遗传变异的患者。

“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.

“PFIC是一种慢性、衰弱的胆汁淤积性肝病，拥有属性胆汁酸升高和瘙痒严重，即使在没有疾病进展的情况下，病人也可以列入肝移植名单。我们很高兴分享多种措施所观察到的长期益处，包括减少瘙痒、血清胆汁酸、改善肝脏健康和P患者的生长Mirum研究与开发负责人Pam Vig博士说，用以前未曾报道过的多种遗传类型的maralixibat治疗FIC。

“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.”.

“我们也很高兴分享OHANA对ICP患者的volixibat研究结果，显示volixibat对胆汁淤积患者血清胆汁酸和瘙痒有明显影响。”。

A summary of these data presented is featured below. Full presentations can be found within the Publications and Presentations section of Mirum’s website.

下面提供了这些数据的摘要。完整的演示文稿可以在Mirum网站的出版物和演示部分找到。

Late-breaker Poster Presentation

断路器海报演示

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

海报5048-C：进行性家族性肝内胆汁淤积症（PFIC）患者使用maralixibat长期维持反应和改善肝脏健康：MARCH-ON研究的2年数据

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.

MARCH-ON扩展研究评估了maralixibat在最初的MARCH研究中接受maralixibat治疗26周并持续长达两年的PFIC患者和接受maralixibat治疗的安慰剂患者的长期疗效和安全性长达一年。在迄今为止研究的最广泛的遗传PFIC类型中，长达两年的maralixibat治疗观察到瘙痒严重程度，血清胆汁酸（sBA）水平，总胆红素和生长的显着和持续改善。

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.

安慰剂-maralixibat组表现出快速（早在3周）和瘙痒严重程度和sBA水平的显着改善，类似于最初的3月-maralixibat组中观察到的那些。没有观察到新的安全信号。最常见的治疗紧急不良事件是GI，发生在治疗早期，并且性质轻微且短暂。

These data suggest overall improved liver health with maralixibat treatment in patients with PFIC that can be maintained long-term..

这些数据表明，对于可以长期维持的PFIC患者，使用maralixibat治疗可以整体改善肝脏健康。。

Other Poster Presentations

其他海报展示

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

海报4602-C：使用maralixibat改善瘙痒症与进行性家族性肝内胆汁淤积患者的生活质量改善相关：来自MARCH-PFIC试验的数据

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.

众所周知，瘙痒是PFIC最繁重的症状之一，发生在大多数患者中，导致睡眠障碍，自残和学校成绩下降，进一步导致生活质量下降。MARCH研究的一个探索性终点是评估用maralixibat治疗后瘙痒的临床显着减少是否与生活质量的改善相关。

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.

这些数据表明临床上显着的瘙痒减少与生活质量的显着改善相关，如在几个领域评估的。maralixibat组在PedsQL，PedsQL SF，PedsQL PF的瘙痒反应者和无反应者之间表现出显着差异，并且FI-T具有显着的趋势。

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..

maralixibat应答者经历了所有HRQoL量表的临床意义改善（MCID>4-5分）。在任何评估中，安慰剂组在瘙痒反应者和无反应者之间没有显着差异。这些数据表明，maralixibat的益处可能超出瘙痒范围，并在生活质量方面产生有意义的改善。。

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

海报4604-C：由于TJP2或MYO5B缺乏，Maralixibat导致进行性家族性肝内胆汁淤积症患儿胆汁淤积性瘙痒的显着改善：来自MARCH-PFIC试验的数据

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).

MARCH研究评估了与PFIC相关的最广泛的遗传类型。PFIC的最常见原因是BSEP（PFIC2），FIC 1，MDR3，TJP2和MYO5B的缺陷。TJP2缺乏症患者易患肝细胞癌。该分析的目的是了解maralixibat在这两种罕见遗传变异（TJP2，n=7，MYO5B，n=4）患者中提供跨疾病关键标志物改善的潜力。

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.

结果表明，所有接受maralixibat治疗的TJP2或MYO5B缺陷患者的瘙痒症状均有显着改善，sBA降低，而接受安慰剂治疗的患者获益甚微。一名接受maralixibat的MYO5B缺乏症参与者的胆红素水平正常化。

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..

MARCH是第一个证明IBAT抑制对TJP2和MYO5B缺陷有益的试验，这些数据支持在这些遗传类型的患者中使用maralixibat。。

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

海报4605-C：在没有基因诊断的情况下，Maralixibat导致进行性家族性肝内胆汁淤积症患儿胆汁淤积性瘙痒的显着改善：来自MARCH-PFIC试验的数据

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.

MARCH研究评估了PFIC临床诊断为无遗传变异的患者（n=8）。该分析的目的是了解maralixibat治疗对临床诊断为PFIC但没有已知遗传变异的患者的疗效和安全性。数据表明，与安慰剂相比，maralixibat与瘙痒，sBA水平，总胆红素和直接胆红素的改善相关。

No new safety signals were observed. These data demonstrate the utility of treating patients with PFIC but without a known genetic variant with maralixibat..

没有观察到新的安全信号。这些数据证明了用maralixibat治疗PFIC但没有已知遗传变异的患者的效用。。

Poster 4547-C: Efficacy, safety and tolerability of volixibat in patients with intrahepatic cholestasis of pregnancy: A case series of 4 patients

海报4547-C:volixibat在妊娠肝内胆汁淤积症患者中的疗效，安全性和耐受性：4例患者的病例系列

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.

妊娠期肝内胆汁淤积症（ICP）是一种影响孕妇的胆汁淤积性肝病。ICP的特征是sBA升高和胆汁淤积性瘙痒，通常会损害睡眠和生活质量。升高的SBA对未出生的胎儿构成重大风险。使用最小吸收的IBAT抑制剂volixibat进行2期开放标签研究OHANA，以评估4例ICP患者的疗效和安全性。

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..

Volixibat表现出瘙痒和sBA水平的改善，表明胆汁淤积性疾病中Volixibat的概念证明。volixibat治疗后未观察到肝酶水平或血液学参数的临床意义变化。最常见的TEAE本质上是GI，短暂的和中等严重程度。。

About LIVMARLI® (maralixibat) oral solution

关于LIVMARLI®（maralixibat）口服溶液

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®（maralixibat）口服液是一种口服，每日一次的回肠胆汁酸转运蛋白（IBAT）抑制剂，是美国食品和药物管理局唯一批准用于治疗Alagille综合征（ALGS）患者胆汁淤积性瘙痒症的药物。年龄在3个月以上。。

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..

LIVMARLI也是欧盟委员会批准用于治疗两个月及以上ALGS患者胆汁淤积性瘙痒症的唯一批准的IBAT抑制剂，以及加拿大卫生部批准用于治疗ALGS胆汁淤积性瘙痒症的IBAT抑制剂。有关美国居民的更多信息，请访问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.

Mirum还提交了LIVMARLI在美国批准三个月及以上的PFIC患者的胆汁淤积性瘙痒症，以及在欧洲批准两个月及以上的PFIC患者。

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..

LIVMARLI目前正在其他罕见胆汁淤积性肝病（包括胆道闭锁）的晚期临床研究中进行评估。LIVMARLI已获得ALGS和PFIC 2型突破性疗法称号，并获得ALGS，PFIC和胆道闭锁的孤儿称号。要了解有关LIVMARLI正在进行的临床试验的更多信息，请访问公司网站上的Mirum临床试验部分。。

IMPORTANT SAFETY INFORMATION

重要的安全信息

LIVMARLI can cause side effects, including:

LIVMARLI可能引起副作用，包括：

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.

肝脏检查的变化。某些肝脏检查的变化在Alagille综合征患者中很常见，并且在用LIVMARLI治疗期间可能恶化。这些变化可能是肝损伤的征兆，可能很严重。您的医务人员应在开始治疗前和治疗期间进行血液检查以检查您的肝功能。

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..

如果您有任何肝脏问题的迹象或症状，包括恶心或呕吐，皮肤或眼睛的白色部分变黄，黑或棕色尿液，胃右侧（腹部）疼痛，请立即告诉您的医疗保健提供者或食欲不振。。

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.

胃和肠（胃肠）问题。LIVMARLI可引起胃和肠问题，包括腹泻，胃痛和治疗期间的呕吐。如果您有任何这些症状比正常情况更频繁或更严重，请立即告诉您的医疗保健提供者。

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..

一种称为脂溶性维生素（FSV）缺乏症的病症是由体内脂肪中储存的某些维生素（维生素A，D，E和K）含量低引起的。FSV缺乏症在Alagille综合征患者中很常见，但在治疗过程中可能会恶化。你的医护人员应该在开始和治疗前进行血液检查。。

Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures.

治疗期间报告的其他常见副作用是消化道出血和骨折。

US Prescribing Information

美国处方信息

EU SmPC

欧盟SmPC

Canadian Product Monograph

加拿大产品专着

About Mirum Pharmaceuticals, Inc.

关于Mirum Pharmaceuticals，股份有限公司。

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.

Mirum Pharmaceuticals，Inc。是一家生物制药公司，致力于改变影响儿童和成人的罕见疾病的治疗方法。Mirum有三种批准的药物：LIVMARLI®（maralixibat）口服液，Cholbam®（胆酸）胶囊和Chenodal®（chenodiol）片剂。

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.

LIVMARLI是一种IBAT抑制剂，被批准用于治疗美国（三个月及以上），欧洲（两个月及以上）和加拿大的Alagille综合征患者的胆汁淤积性瘙痒症。Mirum还提交了LIVMARLI在美国批准三个月及以上的PFIC患者的胆汁淤积性瘙痒症，在欧洲批准两个月及以上的PFIC患者。

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)..

Cholbam是FDA批准用于治疗由于单一酶缺陷引起的胆汁酸合成障碍，以及对出现体征或症状或肝病的患者辅助治疗过氧化物酶体紊乱。Chenodal已获得FDA的医疗必要性认可，可治疗患有脑腱黄瘤病（CTX）的患者。。

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.

Mirum的晚期管道包括三种用于治疗衰弱性肝病的研究性治疗方法。LIVMARLI发展计划包括胆道闭锁的2b期EMBARK研究。Mirum的第二个研究性IBAT抑制剂是volixibat，正在两项潜在的注册研究中进行评估，包括原发性硬化性胆管炎的2b期VISTAS研究和原发性胆汁性胆管炎的2b期VANTAGE研究。

Lastly, Chenodal, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX..

最后，Chenodal已在3期临床研究RESTORE中进行了评估，以治疗CTX患者。。

To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter.

要了解有关Mirum的更多信息，请访问mirumpharma.com，并在Facebook，LinkedIn，Instagram和Twitter上关注Mirum。

Forward-Looking Statements

前瞻性声明

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.

本新闻稿包括有关公司计划参加科学会议的前瞻性声明，包括数据介绍标题和概要，其中可能包括对公司临床和研究数据的讨论，包括我们产品的治疗潜力和/或商业可行性。和各种肝病适应症的产品候选人。

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.

由于此类陈述存在风险和不确定性，因此实际结果可能与此类前瞻性陈述所表达或暗示的结果大不相同。诸如“意志”，“目标”，“潜力”和类似表达之类的词语旨在识别前瞻性陈述。这些陈述的准确性受到许多风险，不确定性和假设的影响，包括但不限于以下因素：研发中固有的不确定性；业务和财务规划固有的不确定性，包括但不限于与Mirum业务和前景相关的风险，我们关注市场的不利发展或美国的不利发展。

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.

或全球监管环境或经济普遍；COVID-19对我们的业务，运营和财务成果的持续影响；和竞争发展。可能导致这种差异的其他因素包括公司与美国证券交易委员会的文件中讨论的因素。本新闻稿中包含的所有前瞻性声明仅在其制定之日起发言，并且基于管理层的假设和估计。这样的日期。

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..

除法律要求外，Mirum不承担更新此类陈述的义务，以反映发生的事件或发生日期之后存在的情况。。

Abbreviations:

缩写：

PedsQL-SF – Social functioning

PedsQL SF–社交功能

PedsQL-PF – Physical functioning

PedsQL PF–物理功能

FI-T – Family Impact Total Scale

FI-T–家庭影响总量表

HRQoL – Health Related Quality of Life

HRQoL–与健康相关的生活质量