About Esperion Therapeutics

Esperion Therapeutics, Inc. operates as a pharmaceutical company. The company singularly focuses on developing and commercializing accessible, oral, once-daily, non-statin medicines for patients struggling with elevated low-density lipoprotein cholesterol, or LDL-C. Through commercial execution and completion of the company’s CLEAR Outcomes trial, as well as advancing the company’s pre-clinical pipeline, the company continues to evolve into a differentiated, global cardiometabolic biotech. The company’s team of lipid experts are dedicated to lowering bad cholesterol through the discovery, development and commercialization of innovative medicines and their combinations with established medicines. The company’s first two products were approved by the U.S. Food and Drug Administration, or FDA, European Medicines Agency, or EMA, and Swiss Agency for Therapeutic Products, or Swissmedic, in 2020. Bempedoic acid and the bempedoic acid / ezetimibe combination tablet are oral, once-daily, non-statin, LDL-C lowering medicines for patients with atherosclerotic cardiovascular disease, or ASCVD, or heterozygous familial hypercholesterolemia, or HeFH. The company recently completed a global cardiovascular outcomes trial, or CVOT, —known as Cholesterol Lowering via BEmpedoic Acid, an ACL-inhibiting Regimen (CLEAR) Outcomes. The trial was designed to evaluate whether treatment with bempedoic acid reduced the risk of cardiovascular events in patients who are statin averse and who have CVD or are at high risk for CVD. The company initiated the CLEAR Outcomes CVOT in December 2016 and fully enrolled the study with over 14,000 patients in August 2019. The primary endpoint of the study was the effect of bempedoic acid on four types of major adverse cardiovascular events, or MACE (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization; also referred to as ‘four-component MACE’). CLEAR Outcomes was an event-driven trial and concluded once the predetermined number of MACE endpoints occurred. On December 7, 2022, the company announced that the study had met its primary endpoint. The company anticipates reporting full results from the study at ACC.23 Annual Scientific Session & Expo together with the World Congress of Cardiology (ACC.23/WCC) on March 4, 2023. The company intends to use results from this CVOT to support submissions for a CV risk reduction indication in the U.S., Europe and other territories; and plans to submit applications for such regulatory approvals in the first half of 2023. Product NEXLETOL is a first-in-class ATP Citrate Lyase, or ACL, inhibitor that lowers LDL-C by reducing cholesterol biosynthesis and up-regulating the LDL receptors. Completed Phase 3 studies conducted in more than 3,000 patients, with over 2,000 patients treated with NEXLETOL, demonstrated an average 18 percent placebo corrected LDL-C lowering when used in patients on moderate or high-intensity statins. NEXLETOL was approved by the FDA in February 2020 as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C. NEXLIZET contains bempedoic acid and ezetimibe and lowers elevated LDL-C through complementary mechanisms of action by inhibiting cholesterol synthesis in the liver and absorption in the intestine. Phase 3 data demonstrated NEXLIZET lowered LDL-C by a mean of 38 percent compared to placebo when added on to maximally tolerated statins. NEXLIZET was approved by the FDA in February 2020 as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C. NILEMDO is a first-in-class ACL inhibitor that lowers LDL-C by reducing cholesterol biosynthesis and up-regulating the LDL receptors. NILEMDO was approved by the EC in March 2020 for use in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in adult patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies as an adjunct to diet in adult patients who are statin-intolerant, or for whom a statin is contraindicated. NUSTENDI contains bempedoic acid and ezetimibe and lowers elevated LDL-C through complementary mechanisms of action by inhibiting cholesterol synthesis in the liver and absorption in the intestine. NUSTENDI was approved by the European Commission (EC) in March 2020 for use in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to diet in combination with a statin in adult patients unable to reach LDL-C goals with the maximum tolerated dose of a statin in addition to ezetimibe, alone in patients who are either statin-intolerant or for whom a statin is contraindicated, and are unable to reach LDL-C goals with ezetimibe alone, or as an adjunct to diet in adult patients already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin. Mechanism of Action In November 2016, the company announced the publication of ‘Liver-specific ATP Citrate Lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis,’ by Pinkosky et al., in Nature Communications. The paper outlines the experiments and analyses undertaken by the company and its collaborators to understand the mechanism of action for how bempedoic acid reduces LDL-C, including its specificity for the liver. Bempedoic acid is an adenosine triphosphate-citrate lyase, or ACL, inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A, or HMG-CoA, reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A, or CoA, activation by very long-chain acyl-CoA synthetase 1, or ACSVL1, to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors. Cardiovascular Disease and Elevated LDL-C The company has developed bempedoic acid and the bempedoic acid / ezetimibe combination tablet as an adjunct to diet and maximally tolerated statin therapy for patients with HeFH or established ASCVD who require additional lowering of LDL-C. The severity of elevated LDL-C in these patients, their level of CVD risk and their therapeutic options all widely vary. The company, with the assistance of a third-party global pharma sales and marketing consultancy group, conducted primary market research and developed a U.S. demand forecast model for bempedoic acid. Other Clinical Studies Global Cardiovascular Outcomes Trial—CLEAR Outcomes CLEAR Outcomes was a Phase 3, event driven, randomized, multicenter, double-blind, placebo-controlled clinical study designed to evaluate whether treatment with bempedoic acid reduces the risk of cardiovascular events in patients with statin intolerance who have cardiovascular disease or are at high risk for cardiovascular disease (CVD). On December 7, 2022, the company announced that the study had met its primary endpoint. The company anticipates reporting full results from the study at ACC.23/WCC on March 4, 2023. The company intends to use results from this CVOT to support submissions for a CV risk reduction indication in the U.S., Europe and other territories; and plans to submit applications for such regulatory approvals in the first half of 2023. Research and Development Expenses The company’s research and development expenses were $118.9 million for the year ended December 31, 2022. Licenses and Collaboration Agreements In April 2008, the company entered into an asset transfer agreement with Pfizer pursuant to which the company acquired all intellectual property owned by Pfizer relating exclusively to the bempedoic acid program. The company also entered into a license agreement providing a worldwide, exclusive, fully paid-up license of certain residual background intellectual property not transferred pursuant to the asset transfer agreement, and the company granted Pfizer (Pfizer Inc.) a worldwide, exclusive, fully paid-up license to certain patent rights owned or controlled by the company relating to development programs other than bempedoic acid. The license to the company covers the development, manufacturing and commercialization of bempedoic acid. On January 2, 2019, the company entered into a license and collaboration agreement, or LCA, with Daiichi Sankyo Europe GmbH (DSE). Pursuant to the agreement, the company has granted DSE exclusive commercialization rights to bempedoic acid and the bempedoic acid / ezetimibe combination tablet in the European Economic Area and Switzerland, or the DSE Territory. DSE will be responsible for commercialization in the DSE Territory. The company remains responsible for clinical development, regulatory and manufacturing activities for the licensed products globally, including in the DSE Territory. On June 18, 2020, the company entered into an amendment to the LCA Amendment with DSE to include Turkey. On April 17, 2020, the company entered into a license and collaboration agreement, or the Otsuka Agreement, with Otsuka Pharmaceutical Co., Ltd., or Otsuka. Pursuant to the Otsuka Agreement, the company granted Otsuka exclusive development and commercialization rights to bempedoic acid and the bempedoic acid / ezetimibe combination tablet in Japan. Otsuka will be responsible for all development, regulatory, and commercialization activities in Japan. On December 3, 2020, the company entered into a definitive agreement with Serometrix to in-license its oral, small molecule PCSK9 inhibitor program. Serometrix developed the oral PCSK9 inhibitor program with its proprietary technology to discover drugs for challenging protein targets. On April 26, 2021, the company entered into a license and collaboration agreement with Daiichi Sankyo Co. Ltd (DS). Pursuant to the agreement, the company granted DS exclusive development and commercialization rights to bempedoic acid and the bempedoic acid / ezetimibe combination tablet in South Korea, Taiwan, Hong Kong, Thailand, Vietnam, Brazil, Macao, Cambodia and Myanmar, or the DS Territory. The agreement allows for potential expansion across geographies, including Saudi Arabia, Kuwait, Oman, UAE, Qatar, Bahrain, Yemen, Colombia and other Latin American countries. Except for certain development activities in South Korea and Taiwan, DS will be responsible for development and commercialization in these territories. Intellectual Property As of December 31, 2022, the company’s patent estate, including patents it owns, on a worldwide basis, included approximately 26 issued United States patents and 16 pending United States patent applications and over 25 issued patents and over 130 pending patent applications in other foreign jurisdictions. Of the company’s worldwide patent estate, only a subset of its patents and pending patent applications relates to the company’s bempedoic acid program. Bempedoic acid is claimed in U.S. Patent No. 7,335,799 that is scheduled to expire in December 2025, which includes 711 days of patent term adjustment, and may be eligible for a patent term extension period of up to five years. The company has requested a five year patent term extension of U.S. Patent No. 7,335,799, and this patent could be the subject of an additional six month pediatric exclusivity period. In addition, U.S. Patent Nos. 9,000,041, 8,497,301, 9,624,152, 10,118,881 and 10,941,095, which are scheduled to expire in December 2023, claim methods of using bempedoic acid. There are seven issued patents in countries outside the United States, including Brazil, Canada, Europe, Japan and Mexico, that relate to bempedoic acid and its use. Furthermore, of the seven granted patents, the company has two granted European patents that have been validated in numerous European countries, including France, Germany, Great Britain, Ireland, Italy, the Netherlands, Spain, Sweden and Switzerland. The company is seeking five year patent term extensions via supplementary protection certificates for 24 national patents validated from one of the granted European patents, which, if approved, could extend the company’s patent protection in those countries until 2028. Additionally, it has one patent family that includes U.S. Patent No. 11,407,705, directed to the method of manufacturing high purity bempedoic acid, one pending U.S. patent application directed to the same, two pending U.S. patent applications directed to compositions of matter of high purity bempedoic acid, and 25 pending patent applications outside of the United States. U.S. Patent No. 11,407,705 and the other patent family members, if issued, are scheduled to expire in June 2040. In addition, the company has three patent families in which it is pursuing patent protection for the company’s bempedoic acid and bempedoic acid / ezetimibe combination tablet in combination with one or more statins. Methods of treating familial hypercholesterolemia with the bempedoic acid / ezetimibe combination tablet are claimed in U.S. Patent No. 10,912,751 that is scheduled to expire in March 2036. The company also has one pending U.S. patent application and 7 issued patents and 17 pending applications outside the U.S. with claims directed to methods of treatment using the bempedoic acid / ezetimibe combination tablet. Additionally, the company has one pending U.S. patent application and 25 pending applications outside of the U.S. directed to the manufacturing of the company’s bempedoic acid / ezetimibe combination tablet. The company also has one issued U.S. patent, one pending U.S. patent application, and six issued patents and 21 pending applications outside the U.S., with claims directed to fixed dose combinations of bempedoic acid and one or more statins and/or methods of using said fixed dose combinations. The company has submitted a request for a patent term extension in the United States for U.S. Patent No. 7,335,799 and has been seeking supplementary protection certificates for one of the granted, counterpart European patents. However, the applicable authorities, including the FDA and the U.S. Patent and Trademark Office, or USPTO, in the United States, and any equivalent regulatory authority in other countries, may not agree with its assessment of whether such extensions are available, and may refuse to grant extensions to the company’s patents, or may grant more limited extensions than it requests. The duration of foreign patents varies in accordance with provisions of applicable local law, but typically is also twenty years from the earliest effective filing date. The company’s issued U.S. patents, including patent term extensions it may be eligible for, will expire on dates ranging from 2023 to mid-2031. Regulatory Matters The company relies on third parties for the production of clinical and commercial quantities of its approved drug and drug candidates in accordance with current good manufacturing practices regulations. While the company has obtained FDA approval for NEXLETOL and NEXLIZET, and approval from the EC and Swissmedic for NILEMDO and NUSTENDI, and whether or not it obtains FDA, EC, or Swissmedic approval for any future product candidate, the company must obtain approval of a product or clinical trial application by the comparable regulatory authorities of foreign countries before it can commence clinical studies or marketing of the product in those countries. History Esperion Therapeutics, Inc. was founded in 2008. The company was incorporated in Delaware in 2008.