Mirum Pharmaceuticals Stock

Mirum Pharmaceuticals, Inc. operates as a biopharmaceutical company. The company focuses on the identification, acquisition, development and commercialization of novel therapies for debilitating rare and orphan diseases. The company focuses on diseases for which the unmet medical need is high and the biology for treatment is clear.

The company’s product, Livmarli, a novel, orally administered, minimally-absorbed ileal bile acid transporter (IBAT) inhibitor (IBATi), is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) one year of age and older in the United States and for the treatment of cholestatic pruritus in patients with ALGS two months and older in Europe. ALGS is estimated to impact one out of every 30,000 births globally. The company markets and commercializes Livmarli in the United States and certain countries in Europe through its specialized and focused commercial team. The company has also entered into license and distribution agreements with several rare disease companies for the commercialization of Livmarli in additional countries. The company is also developing Livmarli for progressive familial intrahepatic cholestasis (PFIC) and biliary atresia (BA). Livmarli has been granted breakthrough therapy designation by the FDA for ALGS and PFIC type 2. The company has submitted positive data from its Phase 3 study of Livmarli in patients with PFIC in a supplemental New Drug Application (sNDA) to the FDA seeking approval for the treatment of cholestatic pruritus in patients with PFIC. The company also expects to report topline data from its EMBARK Phase 2b clinical trial in BA in the second half of 2023.

The company is advancing its second product candidate, volixibat, a novel, oral, minimally-absorbed agent designed to inhibit IBAT, for the treatment of adult patients with cholestatic liver diseases. The company is developing volixibat for the treatment of primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Volixibat has been studied in over 400 adults for up to 48 weeks. Clinical trials of volixibat have shown significant activity on IBAT and bile acid markers, such as 7aC4, fecal bile acids and cholesterol, demonstrating potent biological activity. The company expects to conduct an interim analysis of its VISTAS Phase 2b clinical trial in PSC in mid-2023, and report interim data from its VANTAGE Phase 2b clinical trial in PBC in the second half of 2023.

Livmarli is a novel, orally administered, minimally-absorbed solution approved by the U.S. Food and Drug Administration (FDA) as a once daily medicine for cholestatic pruritus in patients with ALGS one year of age and older and by the European Medicines Agency (EMA) as a once daily medicine for cholestatic pruritus in patients with ALGS two months of age and older. Livmarli is an IBATi that prevents absorption of bile acids in the ileum, thereby lowering serum bile acid (sBA) levels in settings of cholestasis where excess bile acids cause symptomatic and progressive disease burden.

The company incorporated FDA input into the use of the tool in its clinical trials. The company’s validation work with ItchRO(Obs) supports that a change of 1.0 is clinically meaningful.

The company is advancing its product candidate, volixibat, a novel, oral, minimally-absorbed agent designed to inhibit IBAT, for the treatment of adult patients with cholestatic liver diseases. The company is developing volixibat for the treatment of PSC and PBC. Volixibat has been studied in over 400 adults for up to 48 weeks. Clinical trials of volixibat have shown significant activity on IBAT and bile acid markers, such as 7aC4, fecal bile acids and cholesterol, demonstrating potent biological activity.

In November 2018, the company entered into an assignment and license agreement (Shire License Agreement) with Shire International GmbH (Shire), which was subsequently acquired by Takeda Pharmaceutical Company Limited. Pursuant to the Shire License Agreement, Shire assigned, transferred and conveyed all of its right, title and interest in and to the Pfizer Agreement, Satiogen Agreement and Sanofi Agreement, (collectively, the Assigned License Agreements).

In addition, Shire granted the company an exclusive, royalty bearing, sublicensable, worldwide license under certain regulatory materials, as well as patents and know-how, which it refers to collectively as the Shire IP, relating to the Livmarli compound and the volixibat compound in development by Shire as of that date, which it collectively refers to as the Shire Licensed Products, to develop, have developed, make, have made, use, sell, have sold, offer for sale or import the Shire Licensed Products worldwide for the therapeutic or prophylactic application in human health. The company has sole authority and responsibility over development and commercialization activities for the Shire Licensed Products, and it is required to use commercially reasonable efforts to perform certain development, regulatory and commercialization activities with respect to the progressive familial intrahepatic cholestasis (PFIC), ALGS and BA indications for Livmarli and unspecified indications with respect to volixibat.

Through the Shire License Agreement, the company is assigned the rights to the license agreement (Pfizer Agreement), with Pfizer Inc. (Pfizer), pursuant to which it obtained an exclusive, worldwide license to Pfizer’s know-how related to Livmarli, (the Pfizer Know-How). Under the Pfizer Agreement, the company is permitted to research, develop, manufacture and commercialize products utilizing the Pfizer Know-How for the diagnosis, treatment, prevention, mitigation and cure of human diseases and disorders, and to sublicense such rights. Pfizer retained the right to use the Pfizer Know-How to conduct internal research and to use a third party to conduct research on Pfizer’s behalf.

The company has sole responsibility and control over development and commercialization activities for the Pfizer Know-How and products utilizing the Pfizer Know-How, and it is obligated to use commercially reasonable efforts to develop and commercialize products utilizing the Pfizer Know-How. In the event the company determines to sublicense to a third party its right to commercialize the Pfizer Know-How or products utilizing the Pfizer Know-How under the Pfizer Agreement, Pfizer has the first right to negotiate such a commercial license with it.

Through the Shire License Agreement, the company assigned the rights to the license agreement, as amended (Sanofi Agreement), with Sanofi-Aventis Deutschland GmbH (Sanofi), under which it obtained an exclusive, worldwide license to certain patents and know-how controlled by Sanofi related to volixibat (Sanofi Technology). Under the Sanofi Agreement, the company is permitted to develop and commercialize products containing volixibat utilizing the Sanofi Technology. Additionally, under the Sanofi Agreement, the company is permitted to manufacture products containing volixibat utilizing the Sanofi Technology and to sublicense such rights. In addition, Sanofi granted to it, under certain conditions, an exclusive option to obtain an exclusive license to manufacture volixibat during the term of the Sanofi Agreement. The company exercised this option in May 2020 and are transferring manufacturing of volixibat to a third-party contract manufacturer. Sanofi retained the right to practice the Sanofi Technology outside the scope of the license granted to it under the Sanofi Agreement and to make and use for internal research purposes, provided that upon its request, Sanofi is obligated to provide it with a written summary of the results of any such research to the extent such results relate to the use of volixibat as an ASBT inhibitor (ASBTi).

Through the Shire License Agreement, the company was assigned the rights to the license agreement, as amended (Satiogen Agreement), with Satiogen Pharmaceuticals, Inc (Satiogen), under which the company obtained an exclusive, worldwide license to certain patents and know-how controlled by Satiogen related to ASBTis (ASBTi Technology), and TGR5 agonists (TGR5 Technology). Under the Satiogen Agreement, the comopany is permitted to develop, manufacture and commercialize products utilizing the ASBTi Technology or TGR5 Technology for the diagnosis, treatment, prevention, mitigation and cure of human diseases and disorders, other than diabetes, obesity or a combination thereof, and to sublicense such rights. The company has sole responsibility and control over development and commercialization activities for products utilizing the ASBTi Technology or TGR5 Technology under the Satiogen Agreement and it is required to use commercially reasonable efforts to develop and commercialize such licensed products.

Strategy

The key elements of the company’s strategy are to commercialize and advance regulatory approvals of Livmarli for the treatment of ALGS internationally; advance Livmarli through clinical development and seek regulatory approvals for the treatment of PFIC and BA; develop and commercialize volixibat for the treatment of adults with PSC and PBC; and actively manage its product portfolio and expand its pipeline of novel product candidates.

Intellectual Property

The company has developed and continue to develop patent portfolios around its product candidates, Livmarli and volixibat. The company has rights to pending patent applications in the United States, Europe, South Korea, Hong Kong, China, Japan, Mexico and Singapore covering the methods of treating various cholestatic liver indications using maralixibat and/or volixibat which, if issued, would expire in October 2032, absent any patent term adjustments or extensions. The company has rights to two issued patents in the United Stated directed to treating or ameliorating PFIC2 and treating or ameliorating a pediatric disorder characterized by having a non-truncating BSEP mutation selected from PFIC2, BRIC2, and drug induced cholestasis in a pediatric subject comprising administering Livmarli, both of which expire in October 2032. The company has rights to an issued United States Patent No. 11,229,647 in the United States directed to treating ALGS in a pediatric subject comprising administering to the subject about 400 ug/kg/day to about 800 ug/kg/day maralixibat chloride expiring in February 2040. The company has rights to granted and/or issued patents in Australia, Brazil, Canada, China, Israel, Japan, Mexico, South Korea, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Turkmenistan, South Africa and Macau covering the methods of treating cholestasis using IBATis that have limited systemic exposure, which expire in October 2032. The company also has rights to pending patent applications in United States, Europe, Australia, Japan, Eurasia, South Korea, Hong Kong and Singapore, covering methods of treating pediatric cholestatic liver diseases using IBATis that have limited systemic exposure, which, if issued, would expire in October 2032, absent any patent term adjustments or extensions. The company has rights to granted and/or issued patents in Australia, Brazil, Canada, China, Israel, Japan, Mexico, South Korea, South Africa, Singapore, Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, the Slovak Republic, Spain, Sweden, Switzerland, United Kingdom, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Macau and Turkmenistan covering methods of treating pediatric cholestatic liver diseases using IBATis that have limited systemic exposure, which expire in October 2032. The company also has rights to a granted patent in South Africa covering pediatric dosage forms of IBATis that have limited systemic exposure, which expires in October 2032. The company has rights to pending patent applications in the United States, Europe, Canada, China, Japan, South Korea, Israel, Brazil, Russia, Mexico, Australia, New Zealand, UAE, and Saudi Arabia directed to methods for modulating a dosage of an IBATi and to methods for using patient genotype to predict response to IBATi administration in patients with BSEP deficiency. The company has rights to pending applications in the United States, Europe, Canada, China, Japan, South Korea, Israel, Brazil, Russia, Mexico, Australia, New Zealand, UAE, and Saudi Arabia directed to methods for treating cholestatic liver disease comprising administering higher dosages of IBATis. The company has rights to pending applications in the United States, Europe, Canada, China, Japan, South Korea, Israel, Brazil, Russia, Mexico, Australia, New Zealand, UAE, and Saudi Arabia directed to methods of increasing growth in pediatric subjects having cholestatic liver disease by administering IBATis. Any patents issuing from these applications would expire in February 2040, absent any patent term adjustments or extensions. The company has licensed patent applications in the United States and a pending application in Europe from Satiogen covering therapeutic uses of IBATis that have limited systemic exposure for treating inflammatory intestinal conditions, which, if issued, would expire in May 2031, absent any patent term adjustments or extensions. Two of these Satiogen applications issued as United States Patent No. 10,251,880 and 11,260,053, the latter being Orange-Book listable for Livmarli. The company has licensed an issued United States patent, as well as issued foreign counterparts in Argentina, Austria, Australia, Belgium, Canada, Switzerland, China, Germany, Denmark, Spain, Finland, France, the United Kingdom, Greece, Hong Kong, Ireland, Israel, India, Italy, Japan, South Korea, Liechtenstein, Mexico, Malaysia, the Netherlands, Norway, Portugal, Russia, Sweden, Singapore, Taiwan, Turkey, and Brazil from Sanofi, that cover the composition and methods of making volixibat and salts thereof, expiring in December 2027. Patents related to Livmarli and volixibat may be eligible for patent term extensions in certain jurisdictions, including the United States, upon approval of a commercial use of the corresponding product by a regulatory agency in the jurisdiction where the patent was granted and/or issued. Similar to the patent term-extensions in the United States, Supplementary Protection Certificates (SPCs) serve as an extension to a patent right in the European Union for up to five years. Unlike patent term extensions, SPCs apply to extend the protection afforded by the relevant patent solely in relation to the product covered by the marketing authorization.

The company is a party to a number of license agreements under which it is granted intellectual property rights to know-how that are important to its business. The company has licensed know-how related to Livmarli in the United States, Europe and other countries from Pfizer. The company has licensed know-how related to ASBTi Technology and TGR5 Technology from Satiogen. The company has licensed know-how related to volixibat from Sanofi. The company’s existing license agreements as related to Livmarli and volixibat impose various development, regulatory and/ commercial diligence obligations, payment of milestones and/or royalties and other obligations.

In addition, the company has orphan drug designation for Livmarli for the treatment of ALGS, PFIC, PSC and PBC in the United States and the European Union, providing the opportunity to receive seven years of market exclusivity in the United States, which can be extended to seven and a half years if trials are conducted in accordance with an agreed-upon pediatric investigational plan, and ten years of market exclusivity in the European Union, which can be extended to 12 years in the European Union if trials are conducted in accordance with an agreed-upon pediatric investigational plan.

In the United States, maralixibat has been granted new chemical entity (NCE) exclusivity until September 29, 2026. This five years of post-FDA approval exclusivity runs concurrently with its seven years orphan drug exclusivity for the treatment of ALGS. Upon approval in the United States, as volixibat has not previously been approved in the United States for any indication, it may be eligible for five years of NCE exclusivity, which would run concurrently with its seven years of orphan drug exclusivity if the company obtains orphan drug designation for its approved uses.

Sales and Marketing

In addition, the company has built a medical affairs organization and multiple capabilities across North America and Europe to meet the scientific and medical educational needs of the healthcare providers and patients in the rare liver disease community that are focused on providing accurate disease state and balanced product information for appropriate management of patients with rare liver disorders. Medical affairs consists of medical information, patient advocacy, patient diagnosis, medical science liaisons, research and educational grants.

The company has entered into a services agreement with Eversana, a leading provider of commercial support services to the life science industry, to provide integrated nationwide distribution, specialty pharmacy, medical information, patient services and hub support for Livmarli in the United States. Similarly, the company has entered into a service agreement with Movianto to provide integrated distribution outside the United States.

Customers

Livmarli is distributed in the U.S. through a single specialty pharmacy. Sales outside of the U.S. are sold to the company’s authorized distributors. Both the specialty pharmacy and the authorized distributors act as intermediaries between it and the end-users. Further, in 2023, the company began selling Livmarli to pharmacies in certain European countries which act as intermediaries between it and end-users.

Research and Development

The company’s research and development expenses were $106.8 million for the year ended December 31, 2022.

Government Regulation and Product Approval

The company relies on third parties for the production of clinical and commercial quantities of its products in accordance with current good manufacturing practice regulations.

In relation to clinical trials in Europe, the company is subject to Regulation (EU) 2016/679, the General Data Protection Regulation and similar laws in European countries outside of the EU (collectively, the ‘GDPR’), in relation to its collection, control, processing and other use of personal data (i.e. data relating to an identifiable living individual).

History

Mirum Pharmaceuticals, Inc. was founded in 2018. The company was incorporated under the state of Delaware in 2018.