8-K
false 0001759425 0001759425 2022-01-11 2022-01-11

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 OR 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 11, 2022

 

 

Mirum Pharmaceuticals, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38981   83-1281555

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

 

950 Tower LaneSuite 1050

Foster CityCalifornia

    94404
(Address of principal executive offices)     (Zip Code)

Registrant’s telephone number, including area code: (650) 667-4085

N/A

(Former name or former address, if changed since last report.)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading
Symbol(s)

 

Name of each exchange

on which registered

Common stock, par value $0.0001 per share   MIRM   Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company  

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  

 

 

 


Item 2.02

Results of Operations and Financial Condition.

On January 11, 2022, Mirum Pharmaceuticals, Inc. (the “Company”) issued a press release announcing, among other things, the Company’s preliminary unaudited revenues for both the quarter and fiscal year ended December 31, 2021. The full text of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

Item 7.01

Regulation FD Disclosure.

On January 11, 2022, in connection with its participation in the J.P. Morgan Healthcare Conference, the Company posted a corporate slide presentation in the “Investors” portion of its website at www.mirumpharma.com. A copy of the presentation is furnished as Exhibit 99.2 to this Current Report on Form 8-K. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.

The information in this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed to be incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 9.01

Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit

    No.    

  

Description

99.1    Press Release dated January 11, 2022
99.2    Investor Presentation dated January 2022
104    Cover Page Interactive Data File (embedded within the Inline XBRL document)


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

    Mirum Pharmaceuticals, Inc.
Date: January 11, 2022     By:  

/s/ Christopher Peetz

      Christopher Peetz
      President and Chief Executive Officer
EX-99.1

Exhibit 99.1

 

LOGO

Mirum Pharmaceuticals Provides Business Update and Highlights Key 2022 Corporate Milestones

 

   

Unaudited estimated total LIVMARLI net product revenue of $3.0 million for fourth quarter 2021.

 

   

Preliminary cash, cash equivalents, and short-term investments of $261.5 million as of December 31, 2021.

FOSTER CITY, CA – January 11, 2022 – Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today provided a corporate update and highlighted key 2022 milestones in conjunction with its presentation at the 40th Annual J.P. Morgan Virtual Healthcare Conference. The webcast will be live today, Tuesday, January 11, at 1:30 p.m. ET/10:30 a.m. PT via the Investors page on the Company’s website.

“We have had a strong first few months in market with LIVMARLI, the first and only FDA-approved medication for the treatment of cholestatic pruritus in patients one year of age and older with Alagille syndrome. With the excitement and early adoption of this new breakthrough therapy, we achieved preliminary fourth quarter 2021 net product revenue of approximately $3.0 million,” said Chris Peetz, president and chief executive officer at Mirum. “The launch of LIVMARLI is only the beginning of Mirum’s commitment to spearheading innovation for rare diseases worldwide. With a milestone-heavy year for our pipeline, including significant anticipated developments for our LIVMARLI and volixibat programs, we look forward to providing important updates in the coming months and fulfilling our commitment to those living with rare diseases.”

Preliminary unaudited fourth quarter net product revenue*:

Based on preliminary unaudited financial information, Mirum expects total net product revenue from the sale of LIVMARLI for the fourth quarter of 2021 to be approximately $3.0 million. As of December 31, 2021 Mirum had preliminary unaudited cash, cash equivalents, and short-term investments of approximately $261.5 million.

Recent achievements and corporate updates:

 

   

Alagille syndrome

 

   

Successful first quarter of LIVMARLI commercialization with approximately $3.0 million in net product revenue.

 

   

PFIC

 

   

Recruitment completed for Phase 3 MARCH study in progressive familial intrahepatic cholestasis.

 

   

Expanded access program launched.

 

   

Decision not to exercise option for Vivet gene therapy programs resulting in R&D savings in 2022 and 2023.

 

   

Corporate

 

   

Completed sale of priority review voucher for LIVMARLI for $110 million.

Anticipated milestones for Mirum include:

 

   

LIVMARLI

 

   

Launch commercial early access programs in international markets for LIVMARLI in the first half of 2022.

 

   

Topline data from Phase 3 MARCH-PFIC study expected in the second half of 2022.


LOGO

 

   

Alagille syndrome launch in Europe in the second half of the year, if approved by the European Medicines Agency.

 

   

Phase 2b EMBARK study for biliary atresia currently enrolling; topline data anticipated in 2023.

 

   

Volixibat

 

   

Interim analyses expected for VISTAS for primary sclerosing cholangitis.

 

   

First interim analysis expected for OHANA for intrahepatic cholestasis of pregnancy.

 

   

Continued enrollment and country activation for Phase 2b VANTAGE study for primary biliary cholangitis.

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 serious 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.


LOGO

 

Prescribing information

*The Company’s fourth quarter and full year 2021 financial results are preliminary and are subject to the completion of the Company’s 2021 audit. Audited fourth quarter and full year 2021 financial results will be announced in early March.

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare 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. Maralixibat (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 study for progressive familial intrahepatic cholestasis (PFIC) and the EMBARK Phase 2b study for patients with biliary atresia. In addition, Mirum has an expanded access program open in Canada, Australia, the UK and several countries in Europe for eligible patients with Alagille syndrome.

Mirum has submitted a Marketing Authorization Application to the European Medicines Agency for maralixibat for the treatment of cholestatic liver disease in patients with Alagille syndrome.

Mirum’s second investigational treatment, volixibat, also an oral IBAT inhibitor, is being evaluated in three potentially registrational studies including the OHANA Phase 2b study for pregnant women with intrahepatic cholestasis of pregnancy, VISTAS Phase 2b study for adults with primary sclerosing cholangitis, and the VANTAGE Phase 2b study for primary biliary cholangitis.

Follow Mirum on TwitterFacebookLinkedIn and Instagram.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the anticipated launch and timing of the expanded access program for LIVMARLI in international markets, the results, conduct and progress of Mirum’s ongoing and planned studies for its product candidates and the regulatory approval path for its product candidates, the strength of Mirum’s balance sheet and the adequacy of cash and cash equivalents on hand, and continued commercial activities. 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 “plans,” “will,” “may,” “expects,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum’s business in general, the impact of the COVID-19 pandemic, and the other risks described in Mirum’s filings with the Securities and Exchange Commission. 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.


LOGO

 

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.

Contacts

Media Contact:

Erin Murphy

media@mirumpharma.com

Investor Contacts:

Ian Clements, Ph.D.

ir@mirumpharma.com

Sam Martin

Argot Partners

ir@mirumpharma.com

EX-99.2

Slide 1

January 2022 Corporate Presentation Exhibit 99.2


Slide 2

Forward-Looking Statements This presentation contains "forward-looking" statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our business strategy, objectives and opportunities. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements, including, but not limited to, those related to our dependence on third-party clinical research organizations, manufacturers, suppliers and distributors; our ability to obtain necessary additional capital; our ability to obtain necessary regulatory approvals for our products and, if approved, market acceptance of our product; the commercialization plans and expectations for commercializing LIVMARLI in the United States, estimates of the number of patients impacted by ALGS and who are appropriate for treatment with LIVMARLI, the potential benefits of LIVMARLI, the financial impact or revenues from any commercialization we undertake, the impact of competitive products and therapies; our ability to attract and retain key employees; the costs of our commercialization plans and development programs; the design, implementation and outcomes of our clinical trials; our ability to manage the growth and complexity of our organization; our ability to maintain, protect and enhance our intellectual property; and our ability to continue to stay in compliance with applicable laws and regulations.  You should refer to the section entitled “Risk Factors” set forth in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and other filings we make with the Securities and Exchange Commission (SEC) from time to time for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. We undertake no obligation to update any forward-looking statements after the date of this presentation except as may be required by law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Projections, assumptions and estimates of the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. We use our website (www.mirumpharma.com), LinkedIn page (www.linkedin.com/company/mirum-pharmaceuticals), and Twitter account (https://twitter.com/mirumpharma) as channels of distribution of information about our company, product candidates, planned announcements, attendance at upcoming conferences and other matters. Such information may be deemed material information and we may use these channels to comply with our disclosure obligations under Regulation FD. Therefore, investors should monitor our website, LinkedIn page, Twitter account in addition to following our SEC filings, press releases, public conference calls and webcasts.


Slide 3

LIVMARLI FDA-approved for cholestatic pruritus in Alagille Syndrome Robust Pipeline Strong Team and Balance Sheet Leading the Way in Rare Diseases Delivering remarkable treatments to patients in need worldwide $500M+ potential in ALGS in US 5 late-stage indications, significant data events upcoming Leadership track record in identifying & commercializing life-changing medicines


Slide 4

LIVMARLI is Now Approved in the United States LIVMARLI (maralixibat) oral solution is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome one year of age and older. www.LIVMARLI.com


Slide 5

Commercial-Stage with Pipeline of Growth Opportunities LIVMARLI launched, 5 additional indications under development in high-need orphan indications Alagille syndrome* Progressive Familial Intrahepatic Cholestasis Biliary Atresia LIVMARLI (maralixibat) Oral Solution FDA Approved MAA submitted in Europe; anticipated launch H2 2022 Volixibat Phase 1 Approved Preclinical Phase 2b/Phase 3 EMBARK, 2023 data Breakthrough designation PFIC2; MARCH Phase 3, H2 2022 data Primary Sclerosing Cholangitis Intrahepatic Cholestasis of Pregnancy Primary Biliary Cholangitis VISTAS, 2022 interim data OHANA, 2022 interim data VANTAGE, currently screening Phase 1 Approved Preclinical Phase 2b/Phase 3 *Received U.S. FDA approval for cholestatic pruritus in patients with ALGS one year of age and older. In Europe, seeking EMA approval for cholestatic liver disease in patients with ALGS; submission on Sept. 13, 2021


Slide 6

Ileal Bile Acid Transporter (IBAT) Inhibitors Interrupt Bile Acid Recirculation  Targeting Bile Acid Excess of Cholestasis Redirects bile acid flow by inhibiting reuptake by IBAT Interrupts recirculation of bile acids to the liver Increases fecal bile acid excretion Abbreviations: sBA: serum bile acid; IBAT: Ileal bile acid transporter, also known as ASBT or apical sodium-dependent bile acid transporter Clinical effects of IBATi in cholestasis: Reductions in sBA Improvements in pruritus (itch) Improved transplant-free survival


Slide 7

Long-term data set showing significant effects on pruritus and event-free survival LIVMARLI (maralixibat) oral solution for ALGS


Slide 8

ALGS: A Debilitating Disease with Severe Cholestasis Kamath BM, et al. J Pediatr Gastroenterol Nutri. 2018; 67(2): 148-156, 2Vandriel SM, et al. EASL 2020 (oral presentation) Genetic Disease Leading to Severe Cholestasis, Unbearable Pruritus and Multi-system Effects 2k-2.5k Children in the U.S. 88% Affected by cholestatic pruritus; leading indication for liver transplant 6 in 10 Children progress to transplant or death by adulthood


Slide 9

NEW: Significant Improvement in Event-Free Survival in Patients with ALGS with LIVMARLI Compared to Untreated Cohort 6-year analysis demonstrates a 70% reduction for clinical outcomes vs natural history control from the GALA database CI: confidence interval; EFS: event-free survival; HR: hazard ratio; MRX: maralixibat; SAP: statistical analysis plan. *Cox regression models: Primary: Cox regression – effect of MRX vs. GALA log likelihood test adjusted for age, sex, bilirubin, and ALT (according to SAP) EFS: liver transplantation, biliary diversion surgery, hepatic decompensation, or death AASLD 2021 Best of Liver Meeting View the abstract on AASLD’s website


Slide 10

ICONIC: ALGS Pivotal Study Showing Significant Long-term Benefit Gonzales et al., Lancet 2021; 398: 1581–92 Highly Significant, Clinically Meaningful and Sustained Improvements in Pruritus from Baseline *Denotes statistical significance, 95% CI excludes zero (compared with baseline, overall population). †The maralixibat, placebo, maralixibat group (n=16) received placebo during the randomised withdrawal period (purple-shaded area), whereas the maralixibat treatment group (n=13) continued to receive maralixibat.  View data published in recent article in The Lancet


Slide 11

Safety Data of LIVMARLI in ALGS Includes 5 Years of Follow-up from 3 Randomized Studies LIVMARLI Well-Characterized Safety Profile Events observed over 5% of patients Number of events per 100 person-years Diarrhea 41.6 Abdominal pain 38.6 Vomiting 19.8 Nausea 2.9 Fat-soluble vitamin deficiency 11.1 Transaminase increased 6.9 GI bleeding 3.8 Bone fractures 3.3 LIVMARLI Prescribing Information


Slide 12

LIVMARLI Commercialization Strategy Awareness & Use Disease education, unmet need and LIVMARLI clinical data Mirum Access Plus Prescription to fill, reimbursement, exclusive specialty pharmacy Long-term Support Dedicated case management to support adherence, outcomes Comprehensive support from first engagement through initial prescription and continued use


Slide 13

ALGS OPPORTUNITY PRELIMINARY Q4 NET PRODUCT REVENUE* Estimate >90% of covered lives in US have reimbursable pathway as of January 2022 $500M $3.0M LIVMARLI: Approved September 29, 2021 *Unaudited and estimated launch quarter


Slide 14

LIVMARLI Worldwide Commercialization CORE MARKETS US Launched EU Early Access Programs ongoing, Launch anticipated in H2 2022 PARTNER MARKETS DISTRIBUTOR PARTNERS Japan China South Korea Israel Russia Czech Republic (Central & Eastern Europe) UAE (Middle East) In-house Commercial Team


Slide 15

Dramatic and durable response in INDIGO Phase 2 study LIVMARLI (maralixibat) for PFIC


Slide 16

PFIC: Progressive Diseases of Bile-Related Transporters Progressive Familial Intrahepatic Cholestasis (PFIC) Genetic disease of bile transporters, resulting in cholestasis Severe pruritus, common indication for surgery or liver transplant ~20% transplant-free survival at 18 years of age Incidence of 1:50,000 to 1:75,000 births FIC1 BSEP MDR3 PFIC1 PFIC2 PFIC3 Hepatocyte Canalicular membrane Cholesterol Bile acid PFIC sub-types impact different transporters. PFIC2 is the most common.


Slide 17

sBA Response Associated with Improved Pruritus and Growth Adapted from: Thompson R, et al. NASPGHAN 2020 (poster presentation); Error bars represent standard error of the mean. ItchRO[Obs], Itch Reported outcome [Observer]; sBA, serum bile acid NAPPED response threshold 102 µmol/L 85% decrease 80% decrease +0.8 z-score Maralixibat Responders in INDIGO Show Dramatic and Durable Improvements in PFIC2


Slide 18

INDIGO: sBA Response Associated with Transplant-Free Survival Supported by Positive Event-Free Survival Analyses with Natural History Cohort Transplant free survival in PFIC2 after maralixibat treatment Thompson et al, AASLD 2020 Time from enrolment (weeks) TFS (%) 100 60 40 20 80 10 30 50 70 90 0 52 208 260 312 104 156 Log-Rank p=0.0006 sBA Responders


Slide 19

PFIC Phase 3 Enrolling – Topline Data Expected H2 2022 Global Study Covering All PFIC Sub-types; Evaluating High Dose Maralixibat 1:1 randomization Baseline 6 Months + Natural history data set comparisons N~ 30 with nt-PFIC2 Up to 60 patients in supplemental cohort of other PFIC subtypes Global clinical trial, up to ~40 sites Primary Endpoint Pruritus severity in PFIC2 measured by ItchRo(Obs) Secondary Endpoints Pruritus frequency Serum bile acids Safety Additional endpoints Supplemental cohort analyses QOL, growth, other measures Maralixibat 570 μg/kg BID1 Placebo Maralixibat Open label extension 1Patients received doses of 600 µg/kg of maralixibat chloride (equivalent to 570 µg/kg of maralixibat) Abbreviations: BID: twice daily; QoL: Quality of LIfe


Slide 20

Ongoing Phase 2b in post-Kasai Biliary Atresia LIVMARLI (maralixibat) for Biliary Atresia


Slide 21

Biliary Atresia: A Severe Cholestasis Leading to Transplantation Inflammatory bile duct destruction causing severe cholestasis Bile accumulation in the liver leads to liver damage and transplantation Fatal without Kasai procedure (HPE), standard of care within the first weeks of life Leading cause of pediatric liver transplant; 0.5 to 0.8 per 10,000 live births1 Post-Kasai, steroids, antibiotics, immunoglobulins used with no efficacy 1. Sanchez-Valle, A et al. Biliary Atresia Epidemiology, Genetics, Clinical Update, and Public Health Perspective, Advances in Pediatrics 64 (2017), 2Shneider BL, Brown MB, Haber B, et al. A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr. 2006;148(4):467–74; 3Harpavat et al, AASLD 2020) Risk of progression to transplant post-HPE associated with: Bilirubin2 sBA3


Slide 22

EMBARK: Phase 2 Study Enrolling Analyzing 6-month Bilirubin Biomarker Before Long-term Transplant-Free Survival 1:1 randomization Core Study: 6 months Primary Cohort N=72 patients ≤3 months age at HPE Excl. BASM, cystic BA Primary Endpoint Change in total serum bilirubin Secondary Endpoints Change in serum bile acid Bilirubin normalization Biomarkers of liver injury Transplant-free survival Safety Maralixibat 570 μg/kg BID Placebo Extension: 18 months Entry Criteria Core Endpoints Long-term extension All participants receive open-label maralixibat Analyses: transplant-free survival and key liver events


Slide 23

IBATi for Cholestasis in Adults Volixibat


Slide 24

Volixibat Potential in Adult Cholestasis Intrahepatic Cholestasis of Pregnancy (ICP), Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cholangitis (PBC) High Unmet Need Prevalence PSC: ~29,000 in US Limited Tx Options ICP, PSC - No Approved Therapies PBC – Treatments Sub-optimal Byron D, Minuk GY, Hepatology 1996; Bambha et al, Gastroenterology 2003; Geenes V, Williamson C, World Journal of Gastroenterology 2009; Lee et al, J Perinatol. 2006; Jones, 2019 ICP: ~1% of pregnancies Up to ~5% in specific populations PBC: ~130,000 US


Slide 25

Volixibat Highly Active on Bile Acid Excretion Highly active on fecal bile acid excretion Resultant dose-related increase in 7aC4 48-week safety data in prior studies C. Key, AASLD 2019 Broad Data Set Informs Registrational Program Volixibat Markedly Impacts Bile Pathway Selected doses for Phase 2b program 12x – 16x increase


Slide 26

ICP: Bile Acid Accumulation Drives Severe Symptoms, Poor Outcomes Monte et al, 1995; Shaw et al, 1982 Normal Pregnancy ICP Pregnancy Bile acids flow from fetus to mother across a natural placental gradient Maternal cholestasis; Accumulation of bile acids reverses natural bile acid gradient, exposing fetus to toxic bile acids Severe pruritus Risk to Fetus: Preterm labor Stillbirth Other complications


Slide 27

Accumulation of Maternal BAs Drives Fetal Morbidity/Mortality Glantz et al, Hepatology 2004; Geenes et al, Hepatology 2014; Ovadia et al, The Lancet 2019; 2019 March of Dimes Report Card 25-57% $50K $2B ICP babies are born preterm Average cost of preterm birth Annual U.S. medical costs Small differences in sBA increase event risk Each 1.0 µmol/L of sBA, probability of preterm delivery, asphyxia events, and intrapartum meconium passage increases by 1-2%


Slide 28

OHANA: Phase 2b Study Enrolling Evaluating Reductions in sBA, Pruritus and Perinatal Outcomes in ICP 1:1:1 randomization Double-blind Volixibat 20mg Twice Daily Placebo Twice Daily Up to delivery Study Patient Population Primary cohort: N=260 patients with ICP diagnosis  Up to 60 patients in supplemental open-label cohort  ≥18-45 years of age Viable singleton pregnancy Global clinical study Volixibat 80mg Twice Daily Interim Analysis (IA) after N=60 complete study for Efficacy Safety/PK and tolerability Dose selection Post-IA, N~200 for confirmatory phase with 1:1 selected dose : placebo Primary Endpoint Change in sBA from Baseline vs PBO Secondary Endpoints Safety/PK & tolerability Pruritus measures Assessment of adverse perinatal outcomes Additional endpoints Serum markers of disease and pharmacodynamics Additional pruritus measures Additional perinatal outcomes QoL measures


Slide 29

PSC & PBC: Immuno-inflammatory Rare Liver Disease Elevated Bile Acid Levels Drive Severe Symptom Burden and Progressive Liver Disease Obstructed bile flow leads to Severe symptomatic burden Inflammation and fibrosis of the bile ducts and liver Progressive liver damage No approved therapies for PSC No approved therapies for pruritus in PBC PSC: bile ducts inside and outside of the liver; IBD common VISTAS Phase 2b enrolling Obstruction of bile flow via impairment of intrahepatic and extrahepatic bile ducts PBC: bile ducts inside the liver VANTAGE Phase 2b enrolling


Slide 30

VISTAS: Volixibat PSC Phase 2b Enrolling Assessing Pruritus Reductions in PSC; Setting with No Approved Therapies 1:1:1 randomization Volixibat 20 mg Twice Daily Placebo (PBO) Twice Daily Day 1 28 weeks Study Patient Population ~120 PSC patients (small duct compensated cirrhosis, concomitant IBD allowed) Moderate-to-severe pruritus No biopsy or ALP cutoff Global clinical study Volixibat 80 mg Twice Daily Interim Analysis: 1. Efficacy 2. Safety and tolerability 3. Dose selection for pivotal phase Post-IA, confirmatory phase with 1:1 selected dose : placebo  Volixibat Open- Label Extension Primary Endpoint Change in pruritus from Baseline vs PBO by Adult ItchRO score Secondary Endpoints Safety & tolerability Other pruritus/itch measures Quality of Life measures Serum bile acids Additional endpoints Additional itch and QoL measures Fibrosis markers & transient elastography


Slide 31

VANTAGE: Volixibat PBC Phase 2b Study - Enrolling Evaluating the safety and efficacy of volixibat in patients with itch caused by PBC  1:1:1 randomization Volixibat BID – 20 mg Placebo (PBO) BID 28wk Study Patient Population N = 260 PBC patients Moderate-to-severe pruritus No ALP cutoff Stable doses of UDCA, Fibrates allowed Global clinical study Volixibat BID – 80 mg Interim Analysis at week 16, n~60: 1. Efficacy 2. Safety and tolerability 3. Dose selection for pivotal phase Post-IA, confirmatory phase with 1:1 selected dose : placebo  Volixibat Open Label Extension (OLE) for up 2 years Primary Endpoint Change in pruritus from Baseline vs PBO by Adult ItchRO score Secondary Endpoints Safety & tolerability Other pruritus/itch measures Quality of Life (QoL) measures Serum markers of disease (ALP) Serum bile acids Additional endpoints Additional itch and QoL measures Serum markers of disease modification Day 1


Slide 32

Leading the Way in Rare Liver Disease Mirum


Slide 33

Opportunity to Significantly Expand in Pipeline Indications PATIENT POPULATION ALGS ALGS ALGS +PFIC +BA PFIC BA FDA-approved, EU Marketing submission complete Pediatric indications Pediatric indications + adult indications Pediatric indications (blue) Adult indications (red) >20x increase  +VOLIXIBAT (ICP, PSC, PBC)


Slide 34

Strong Balance Sheet: Projected 3+ Years Runway SELECTED Balance Sheet Data Sept. 30, 2021 Dec. 31, 2020 Cash, cash equivalents and investments $      205.0 231.8 Total Assets 235.2 240.9 Total stockholders’ equity (deficit) 56.4 172.1 SELECTED Statements of Operations Data Sept. 30, 2021 Sept. 30, 2020 Licensing revenue $     5.0 $      - Operating expenses: Research and development 30.5 16.0 General and administrative 17.4 5.7 Total operating expenses 47.8 21.7 Net loss (47.1) (21.5) $ in millions Three Months Ended Monetized priority review voucher in conjunction with approval for $110 million As of December 31, 2021 Mirum had cash, cash equivalents, and short-term investments of $261.5 million* *Preliminary and unaudited


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Potential ALGS partner market approvals (Q4) Mirum: Transformative Milestones Ahead in 2022 OHANA (ICP) interim analysis (H2) VISTAS (PSC) interim analysis (H2) MARCH-PFIC Phase 3 data (H2) International early access programs (Q1) Potential ALGS EU approval* (H2) *In Europe, seeking EMA approval for cholestatic liver disease in patients with ALGS LIVMARLI VOLIXIBAT


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LIVMARLI FDA-approved for cholestatic pruritus in Alagille Syndrome Robust Pipeline Strong Team and Balance Sheet Leading the Way in Rare Diseases Delivering remarkable treatments to patients in need worldwide $500M+ potential in ALGS in US 5 late-stage indications, significant data events upcoming Leadership track record in identifying & commercializing life-changing medicines


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Thank you! ©2021 Mirum Pharmaceuticals, Inc. All rights reserved. All service marks, trademarks and tradenames appearing in this presentation are the property of their respective owners. Solely for convenience, the trademarks and tradenames referred to in this presentation appear without the ® and ™ symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or the right of the applicable licensor to these trademarks and tradenames. The information herein is for informational purposes only and represents the current view of Mirum Pharmaceuticals, Inc. as of the date of this presentation (or as of an earlier date if specifically noted).


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LIVMARLI (maralixibat) oral solution Important Safety Information Important Safety Information LIVMARLI can cause serious side effects, including: Changes in liver tests: Changes in certain liver tests are common in patients with Alagille syndrome but may worsen during treatment with Livmarli. These changes may be a sign of liver injury and can be serious. Your health care provider should do blood tests before starting and during treatment to check your liver function. Stomach and intestinal (gastrointestinal) problems: LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Fat Soluble Vitamin Deficiency: This vitamin deficiency is common in patients with Alagille syndrome but may worsen during treatment.