About Intercept Pharmaceuticals

Intercept Pharmaceuticals, Inc. operates as a biopharmaceutical company. The company focuses on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases with high unmet medical need utilizing the company’s proprietary bile acid chemistry. The company’s first marketed product, Ocaliva (obeticholic acid or ‘OCA’), is a farnesoid X receptor (‘FXR’) agonist approved in the United States, the United Kingdom, the European Union, and several other jurisdictions for the treatment of primary biliary cholangitis (‘PBC’) in combination with ursodeoxycholic acid (‘UDCA’) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA. On July 1, 2022, the company completed the sale of its ex-U.S. commercial operations to Advanz Pharma and its affiliates (collectively, ‘Advanz’), and sublicensed the right to commercialize Ocaliva and OCA for nonalcoholic steatohepatitis (‘NASH’) outside of the United States. In addition to commercializing OCA for PBC under the Ocaliva brand name, the company is developing OCA for additional indications, including NASH. The company is also developing product candidates in various stages of clinical and preclinical development. OCA and the company’s other product candidates have the potential to treat orphan and other more prevalent liver diseases, such as NASH for which there are limited therapeutic options. Ocaliva was approved for PBC by the U.S. Food and Drug Administration (‘FDA’) in May 2016 under the accelerated approval pathway. The company commenced sales and marketing of Ocaliva in the United States shortly after receiving approval, and Ocaliva is available to U.S. patients primarily through a network of specialty pharmacy distributors. Ocaliva received conditional approval for PBC from the European Commission in December 2016. Since January 2017, Ocaliva has also received regulatory approval in several markets outside the United States and Europe, including (but not limited to) Canada, Israel and Australia. Ocaliva received orphan drug designation in both the United States and the European Union for the treatment of PBC. In addition, the company continues to work to execute on its post-marketing regulatory commitments with respect to Ocaliva. In June 2022, the company announced topline results from its COBALT trial. The primary endpoint, as agreed with the FDA, was time to first occurrence of any of the following clinical endpoints: all-cause death, liver transplant, hospitalization for other serious liver-related events, signs of progression to hepatic decompensation, or signs of development of portal hypertension. The study did not demonstrate a statistically significant difference between Ocaliva and placebo on the primary endpoint: 71 subjects in the Ocaliva arm progressed to clinical events compared to 80 in the placebo arm (p=0.30; HR 0.84). The safety and tolerability of Ocaliva were consistent with its known profile and adverse events were in line with expectations for patients with advanced PBC based on the natural history of the disease. In June 2022, the company also announced topline results for the company’s HEROES-US study, a retrospective real-world study that evaluated data from a U.S. claims database, to compare clinical outcomes in a pre-defined group of patients with PBC who were treated with Ocaliva and a comparable group of PBC patients who were eligible, but who were not treated with Ocaliva. The results from the HEROES-US study showed a statistically significant and clinically meaningful reduction in all-cause death, liver transplant, or hospitalization for hepatic decompensation among Ocaliva-treated patients compared to the control group. In September 2022, the company had a supplemental NDA (‘sNDA’) pre-submission meeting with the FDA in which the company reviewed its post-marketing requirements with respect to Ocaliva. The company intends to submit the data from the COBALT and HEROES-US studies, as well as additional data, including data from other real world evidence studies, as part of a broader evidence package in the sNDA in the support of full approval of Ocaliva for the treatment of PBC, which the company anticipates submitting to the FDA in 2023. If this data package does not support fulfillment of the company’s post-marketing obligations, the company may not be able to maintain the company’s previously granted marketing approval of Ocaliva for PBC. The company’s lead development product candidate is OCA for the potential treatment of NASH. In February 2019, the company announced topline results from the planned 18-month interim analysis of the company’s pivotal Phase 3 clinical trial of OCA in patients with liver fibrosis due to NASH, known as the REGENERATE trial (the ‘Original Analysis’). The REGENERATE trial is ongoing and is expected to continue through clinical outcomes for verification and description of the clinical benefit of OCA. In June 2020, the company received a complete response letter (‘CRL’) from the FDA stating that the company’s NDA for OCA for the treatment of liver fibrosis due to NASH could not be approved in its present form. The company had its end of review meeting with the FDA in October 2020 to discuss the FDA’s risk-benefit assessment in the CRL based on its review of the available data, as well as the company’s proposed resubmission of its NDA for the treatment of liver fibrosis due to NASH. The meeting was constructive and the FDA provided the company with helpful guidance regarding supplemental data the company could provide to further characterize OCA’s efficacy and safety profile that could support resubmission based on the company’s Phase 3 REGENERATE 18-month biopsy data, together with a safety assessment from the company’s ongoing studies. Following the company’s end of review meeting, the company had a dialogue with FDA regarding the REGENERATE study to clarify data, a new consensus read methodology for liver biopsies, and analyses required to re-submit the company’s NDA. In connection with the resubmission of the company’s NDA, it conducted a new interim analysis of the company’s ongoing pivotal Phase 3 REGENERATE trial of OCA using a biopsy consensus read methodology in the same intent-to-treat (‘ITT’) population as the Original Analysis (the ‘New Interim Analysis’). In July 2022, the company announced topline results from the New Interim Analysis. In July 2022, the company had a pre-submission meeting with the FDA in which the company reviewed the planned structure and the timing of the submission of its NDA and had an ongoing dialogue as the company prepared to re-submit. The company will need to overcome the risk-benefit assessment of the FDA from the prior review of the NDA for OCA for the treatment of liver fibrosis due to NASH. In September 2022, the company announced that REVERSE, a Phase 3 study evaluating the safety and efficacy of OCA in patients with compensated cirrhosis due to NASH, did not meet its primary endpoint of a greater than or equal to 1-stage histological improvement in fibrosis with no worsening of NASH following up to 18 months of therapy. In December 2022, the company re-submitted an NDA to the FDA for OCA for the treatment of patients with pre-cirrhotic liver fibrosis due to NASH. The resubmission is supported by a robust body of evidence from the OCA NASH clinical development program, including two positive interim 18-month analyses from the pivotal Phase 3 REGENERATE study in patients with pre-cirrhotic liver fibrosis due to NASH. In January 2023, the company announced that the FDA accepted its NDA for OCA seeking accelerated approval for the treatment of patients with pre-cirrhotic liver fibrosis due to NASH. The FDA indicated that it considers this a complete, Class 2 resubmission and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 22, 2023, for the NDA. The timeline for the review of the NDA by the FDA remains subject to change. The company is evaluating the efficacy, safety and tolerability of OCA in combination with bezafibrate in patients with PBC in a Phase 2 study outside of the United States that has completed enrollment. In the United States, the company has an ongoing Phase 1 study to better characterize the exposure response of the fixed-dose combination, which has completed enrollment, and the company has an open Investigational New Drug (‘IND’) application with the FDA. The company is also conducting a second Phase 2 study evaluating a fixed-dose combination of OCA and bezafibrate for the treatment of patients with PBC who have not achieved an adequate biochemical response to UDCA. The company’s longer-term goal is developing and seeking regulatory approval for a fixed dose combination regimen in PBC and potentially in other diseases. In addition, the company has other compounds in early stages of research and development in its pipeline, including the company’s INT-787 compound, an FXR agonist. The company is evaluating INT-787 in a Phase 2a clinical trial. The company submitted an IND for INT-787 in the first half of 2022, which is now active. Strategy The key elements of the company’s strategy are to further strengthen the company’s foundational PBC business; execute its clinical and regulatory goals and timelines; expand the company’s portfolio and pipeline; improve the company’s operational foundation; and expand and protect the company’s intellectual property. Licenses and Collaborations The company entered into a Sublicense Agreement with Advanz (the ‘Sublicense Agreement’) under which the company agreed to continue to conduct certain post-marketing work and other activities with respect to Ocaliva for PBC, including continuing to conduct certain PBC studies (the ‘PBC Post-Marketing Work’). The company also entered into a Supply and Manufacture Agreement with Advanz (the ‘SMA’) under which the company has an obligation to supply Advanz with OCA in bulk tablet form and continue to be responsible for the manufacturing and supply of OCA globally while Advanz is responsible for packaging, distribution and commercialization of the therapy in all markets outside of the United States. First Approved Product Ocaliva Ocaliva was approved for PBC by the FDA in May 2016 under the accelerated approval pathway. The company commenced sales and marketing of Ocaliva in the United States shortly after receiving approval, and Ocaliva is now available to the U.S. patients primarily through a network of specialty pharmacy distributors. Ocaliva received conditional approval for PBC from the European Commission in December 2016. Since January 2017, Ocaliva has also received regulatory approval in several markets outside the United States and Europe, including (but not limited to) Canada, Israel and Australia. Ocaliva received orphan drug designation in both the United States and the European Union for the treatment of PBC. Phase 3 POISE Trial Ocaliva’s accelerated approval in the United States and conditional approval in the European Union was supported by the results of the company’s Phase 3 POISE trial, which was completed in March 2014. Following the completion of the double-blind portion of the POISE trial described above, patients were given the option to enroll in a five-year open-label long-term safety and efficacy extension trial, which has been completed. In November 2021, the company presented the results of an analysis of clinical outcomes in patients with PBC treated with Ocaliva in the POISE Phase 3 study and its open label extension compared to propensity score matched external controls from the U.K. and Global PBC cohorts, as a late-breaking podium presentation at The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The study results showed statistically significant greater transplant-free survival in patients receiving obeticholic acid as compared to the control groups. Ongoing Confirmatory Clinical Outcomes Trial and Other Post Marketing Requirements In connection with Ocaliva’s accelerated approval in the United States and conditional approval in the European Union, in December 2014, following discussions with the FDA, the company initiated its Phase 4 confirmatory outcomes trial of Ocaliva for PBC, known as the COBALT trial, and other clinical trials to satisfy post-marketing regulatory requirements. The COBALT trial was designed to evaluate subjects across the spectrum of PBC disease, including early and advanced PBC. The company also agreed to evaluate the safety and efficacy of Ocaliva in patients with moderate to severe hepatic impairment in a study known as the 401 trial and as monotherapy in patients with PBC. In addition, the company agreed to develop and characterize a lower dose formulation of Ocaliva to allow for once daily dosing in patients with moderate or advanced hepatic impairment. Continued approval of Ocaliva for PBC is contingent upon the verification and description of clinical benefit in the COBALT trial and the company’s satisfaction of the company’s other post-marketing regulatory requirements. Any delay or failure by the company to satisfy such requirements may jeopardize the continued approval of Ocaliva for PBC in the United States or other jurisdictions. Further, as part of the company’s post-marketing requirements for Ocaliva, the company undertook a Phase 4 clinical trial of Ocaliva in patients with PBC who have moderate to severe hepatic impairment (Child-Pugh B and C) (known as the 401 trial). This double-blind, placebo-controlled study was designed to evaluate the pharmacokinetics of Ocaliva and its conjugates, as well as safety and tolerability. The company also agreed with the FDA and the European Medicines Agency (‘EMA’) to terminate the company’s 401 trial, in light of the exclusion of patients with PBC with decompensated cirrhosis from the Ocaliva label in the U.S. In addition, a data monitoring committee (‘DMC’) reviewed the unblinded results of a pre-specified interim efficacy analysis of the COBALT trial and separately reviewed unblinded safety and pharmacokinetic data from both the COBALT and 401 trials. In June 2022, the company announced topline results from the company’s COBALT trial. In June 2022, the company also announced topline results for the company’s HEROES-US study, a retrospective real-world study that evaluated data from a U.S. claims database, to compare clinical outcomes in a pre-defined group of patients with PBC who were treated with Ocaliva and a comparable group of PBC patients who were eligible, but who were not treated with Ocaliva. In September 2022, the company had a supplemental NDA (‘sNDA’) pre-submission meeting with the FDA in which the company reviewed its post-marketing requirements with respect to Ocaliva. The company intends to submit the data from the COBALT and HEROES-US studies, as well as additional data, including data from other real world evidence studies, as part of a broader evidence package in the sNDA in the support of full approval of Ocaliva for the treatment of PBC, which the company anticipates submitting to the FDA in 2023. If this data package does not support fulfillment of the company’s post-marketing obligations, the company may not be able to maintain its previously granted marketing approvals of Ocaliva for PBC. Other Regulatory Information In October 2016, the Committee for Medicinal Products for Human Use (the ‘CHMP’) of the EMA adopted a positive opinion recommending the granting of a conditional marketing authorization of Ocaliva in PBC. Based on the CHMP’s positive recommendation, the European Commission granted a conditional marketing authorization of Ocaliva in PBC in December 2016. Therefore, in accordance with applicable regulations, the PBC marketing authorization required demonstration of compliance with all measures included in an EMA-approved Pediatric Investigation Plan for OCA for the treatment of biliary atresia, a pediatric cholestatic disease. The company does not have a REMS for Ocaliva for the treatment of PBC. Ocaliva Label Update In the course of the company’s post-marketing pharmacovigilance activities, deaths have been reported in PBC patients with moderate or severe hepatic impairment. In an analysis performed by the company and in consultation with the FDA, the company concluded that certain of these patients were prescribed once daily doses of Ocaliva, which is seven times higher than the recommended weekly dose in such patients. As a result, in September 2017, the company issued a Dear Health Care Provider (‘DHCP’) letter, and the FDA also subsequently issued its own drug safety communication to reinforce recommended label dosing. Both communications remind healthcare providers of the importance of the recommended reduced dosing of Ocaliva in PBC patients with moderate or severe hepatic impairment, while reiterating the importance of monitoring PBC patients for progression of their disease and the occurrence of liver-related adverse reactions. In addition to the DHCP letter, the company tooks actions to enhance education about appropriate use of Ocaliva. These initiatives included: reeducating physicians on the label, with a focus on ensuring appropriate dosing for patients with moderate or severe hepatic impairment; enhancing monitoring of patients for liver-related adverse reactions; and adjudicating reported cases of serious liver injury, including in patients with no or mild hepatic impairment. In February 2018, the company announced that the Ocaliva label in the United States had been updated by the FDA to include a boxed warning and a dosing table that reinforced the then-existing dosing schedule for patients with Child-Pugh Class B or C or decompensated cirrhosis. In addition, the FDA issued an updated drug safety communication to accompany the revised label. The company remains focused on the safety of all of the patients using Ocaliva within and outside of the company’s ongoing clinical studies and have engaged with relevant regulatory authorities to ensure that the Ocaliva label sufficiently reinforces the importance of appropriate dosing in patients with advanced cirrhosis. The FDA notified the company that, in the course of its routine safety surveillance, in May 2020 the FDA began to evaluate a newly identified safety signal, or NISS, regarding liver disorder for Ocaliva which the FDA classified as a potential risk. The FDA informed the company that its review of the NISS was focused on a subset of the cirrhotic, or more advanced, PBC patients who had taken Ocaliva. As part of the company’s routine pharmacovigilance efforts, the company worked with the FDA to reconcile the company’s internal safety database with the FDA Adverse Event Reporting System database and the company completed a comprehensive assessment of all available data, including data from the company’s completed clinical trials, blinded reviews of ongoing clinical trial data, unblinded reviews of certain ongoing clinical trial data by the DMC, post-marketing data and natural history data, which the company submitted to the FDA and had a meeting in 2021 to discuss. In May 2021, the NISS process was concluded and the company aligned with the FDA on updated Ocaliva prescribing information in the United States, and Ocaliva is now contraindicated for patients with PBC and decompensated cirrhosis, a prior decompensation event, or compensated cirrhosis with evidence of portal hypertension, in addition to the existing contraindication for complete biliary obstruction. Product Candidates OCA for liver fibrosis due to NASH The company’s lead product candidate is OCA for the potential treatment of liver fibrosis due to NASH. In February 2019, the company announced topline results from the Original Analysis of the company’s REGENERATE trial. The REGENERATE trial, which studies subjects with pre-cirrhotic liver fibrosis due to NASH, is ongoing and is expected to continue through clinical outcomes for verification and description of the clinical benefit of OCA. In the primary efficacy analysis, once-daily OCA 25 mg met the primary endpoint agreed with the FDA of fibrosis improvement by at least one stage with no worsening of NASH at the planned 18-month interim analysis. Adverse events were generally mild to moderate in severity and the most common were consistent with the known profile of OCA. OCA has received breakthrough therapy designation from the FDA for the treatment of NASH patients with liver fibrosis. In September 2019, the company submitted an NDA seeking accelerated approval of OCA for liver fibrosis due to NASH in the United States. In December 2019, the company submitted a MAA seeking conditional approval of OCA for liver fibrosis due to NASH in Europe. The FDA subsequently accepted the company’s NDA for filing and granted a priority review designation for OCA for liver fibrosis due to NASH. In January 2020, the EMA validated the company’s MAA and thereby confirmed that its MAA was sufficiently complete to begin the formal review process. In June 2020, the company received a complete response letter (‘CRL’) from the FDA stating that its NDA for OCA for the treatment of liver fibrosis due to NASH could not be approved in its present form. At that time, the FDA recommended that the company submits additional post-interim analysis efficacy and safety data from the ongoing REGENERATE trial in the support of potential accelerated approval and that the long-term outcomes phase of the trial should continue. In October 2020, the company had its end of review meeting with the FDA to discuss the FDA’s risk-benefit assessment in the CRL based on its review of the available data, as well as the company’s proposed resubmission of its NDA for the treatment of liver fibrosis due to NASH. The meeting was constructive and the FDA provided the company with helpful guidance regarding supplemental data the company could provide to further characterize OCA’s efficacy and safety profile that could support resubmission based on the company’s Phase 3 REGENERATE 18-month biopsy data, together with a safety update from the company’s ongoing studies. Following the company’s end of review meeting, the company had a dialogue with FDA regarding the REGENERATE study to clarify data, a new consensus read methodology for liver biopsies, and analyses required to re-submit the company’s NDA. In connection with the resubmission of the company’s NDA, the company conducted the ‘New Interim Analysis’. Based on the results of the New Interim Analysis, in December 2022, the company re-submitted its NDA for OCA in pre-cirrhotic liver fibrosis due to NASH. In addition, the company has conducted a number of other trials and studies in connection with the company’s NASH development program, and announced topline data from the company’s Phase 3 trial in NASH patients with compensated cirrhosis, known as the REVERSE trial. Phase 3 REGENERATE Trial The company is conducting a pivotal Phase 3 clinical trial of OCA in patients with liver fibrosis due to NASH, known as the REGENERATE trial. REGENERATE is a randomized, double-blind, placebo-controlled, multicenter study assessing the safety and efficacy of OCA on liver-related clinical outcomes in patients with liver fibrosis due to NASH. Patients with biopsy proven NASH with fibrosis are randomized 1:1:1 to receive placebo, OCA 10 mg or OCA 25 mg once daily. In August 2019, the company announced the completion of the enrollment of the clinical outcomes cohort of REGENERATE, with 2,480 adult NASH patients with fibrosis randomized at over 300 qualified centers worldwide. REGENERATE will continue through clinical outcomes for verification and description of clinical benefit. The end-of-study analysis will evaluate the effect of OCA on all-cause mortality and liver-related clinical outcomes. In February 2019, the company announced topline results from the REGENERATE trial interim analysis. In July 2022, the company announced topline results from the New Interim Analysis. In July 2022, the company had a pre-submission meeting with the FDA in which the company reviewed the planned structure and the timing of the submission of the company’s NDA and had an ongoing dialogue as the company prepared to re-submit. The company will need to overcome the risk-benefit assessment of the FDA from the prior review of the NDA for OCA for the treatment of liver fibrosis due to NASH. Phase 3 REVERSE Trial The company conducted a Phase 3 clinical trial in NASH patients with compensated cirrhosis, known as the REVERSE trial. REVERSE is a randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of OCA in NASH patients with compensated cirrhosis. In January 2020, the company announced that it completed enrollment of the REVERSE trial with over 900 patients with a biopsy-confirmed diagnosis of cirrhosis due to NASH randomized. In September 2022, the company announced that REVERSE, a Phase 3 study evaluating the safety and efficacy of OCA in patients with compensated cirrhosis due to NASH, did not meet its primary endpoint of a greater than or equal to 1-stage histological improvement in fibrosis with no worsening of NASH following up to 18 months of therapy. The company will continue to work with REVERSE investigators to analyze the data from both the double-blind portion of the study, as well as the open-label extension phase of REVERSE. Phase 2 CONTROL Trial In December 2015, the company initiated a Phase 2 clinical trial, known as the CONTROL trial, to characterize the lipid metabolic effects of OCA and cholesterol management effects of concomitant statin administration in NASH patients. In July 2017, the company announced that CONTROL met its primary objective by showing that newly initiated treatment with atorvastatin rapidly reversed OCA-associated increases in LDL cholesterol to below baseline levels. Phase 2 Sumitomo Dainippon Trial In October 2015, the company announced the results of a 72-week Phase 2 dose ranging trial of OCA in 200 adult patients with NASH in Japan. The trial was conducted by the company’s former collaborator, Sumitomo Dainippon Pharma Co., Ltd. (‘Sumitomo Dainippon’). Phase 2b FLINT Trial In November 2014, the results from a Phase 2b clinical trial for the treatment of NASH, known as the FLINT trial, which was sponsored by the NIDDK, a part of the National Institutes of Health, were published in The Lancet. The FLINT trial was a double-blind, placebo-controlled trial of a once-daily dose of OCA 25 mg or placebo given for 72 weeks in 283 patients with biopsy-proven NASH. OCA achieved the primary endpoint in the FLINT trial, which was defined as an improvement of two or more points in NAS with no worsening of liver fibrosis. OCA and Bezafibrate In December 2018, the company entered into an agreement (the ‘Aralez Agreement’) with Aralez Pharmaceuticals Canada Inc. (‘Aralez’), pursuant to which the company acquired Aralez’s license to develop and commercialize bezafibrate in the United States (as amended and restated in connection therewith, the ‘Bezafibrate License’); Aralez’s IND on file with the FDA and other associated regulatory documentation; and a non-exclusive license to certain of Aralez’s intellectual property. Bezafibrate, a PPAR agonist that has been studied in PBC, is not approved in the U.S. for any indication. The company is evaluating the efficacy, safety and tolerability of OCA in combination with bezafibrate in patients with PBC in a Phase 2 study outside of the United States that has completed enrollment. In the United States, the company has an ongoing Phase 1 study to better characterize the exposure response of the fixed-dose combination, which has completed enrollment, and the company has an open IND application with the FDA. The company is also conducting a second Phase 2 study evaluating a fixed-dose combination of OCA and bezafibrate for the treatment of patients with PBC who have not achieved an adequate biochemical response to UDCA. The company’s longer-term goal is developing and seeking regulatory approval for a fixed dose combination regimen in PBC and potentially in other diseases. Other Product Candidates The discovery and development of safe and effective new product candidates and the development of additional uses for the company’s existing product candidates and approved products, are important for the continued strength of the company’s business. The company, together with its collaborators, have discovered several bile acid chemistry-based compounds that are in the early stages of research and development. Among these compounds is INT-787, which is an FXR agonist that the company is evaluating in a Phase 2a clinical trial. The company submitted an IND for INT-787 in the first half of 2022, which is now active. INT-787 has distinct pharmacological properties that differ from those of OCA and has shown potential anti-fibrotic and anti-inflammatory effects in animal models. As of February 2023, the company had completed recruitment of the company’s Phase 1 study. In November 2022, the company announced plans to focus development of INT-787 in severe alcohol-associated hepatitis (sAH). The company has also initiated the FRESH (FXR Effect on Severe Alcohol-Associated Hepatitis) study, a Phase 2a trial evaluating the safety, tolerability, efficacy and pharmacokinetics of INT-787 in subjects with sAH. The Phase 2a FRESH study is a randomized, double-blind, dose-escalation study that is expected to enroll approximately 50 patients with sAH across multiple clinical sites in the U.S., UK and France. The study aims to demonstrate and provide rationale for the selection of optimal dose(s) of INT-787 in the target patient population. INT-787 will be evaluated for safety and tolerability prior to dose escalation. Overall early efficacy, based on the Lille score at Day 7 compared to placebo, will be assessed for each dose cohort, as well as change in MELD score and mortality. Intellectual Property The company is the owner of record of numerous issued U.S. patents and non-U.S. patents (some of which are sublicensed to Advanz, for which the company remains responsible for patent filing, prosecution and maintenance, pursuant to the terms of the company’s Sublicense Agreement with Advanz) with claims directed to pharmaceutical compounds, pharmaceutical compositions, methods of making these compounds and methods of using these compounds in various indications. In addition, the company is the owner of record of numerous pending U.S. and non-U.S. patent applications, and regularly pursue additional patent applications in various jurisdictions. The company also has numerous trademark and service mark registrations and pending trademark and service mark applications in the United States and abroad. The patent portfolio for OCA contains U.S. and non-U.S. patents and patent applications directed to compositions of matter, methods of use and manufacturing methods. The company’s primary composition of matter patent for OCA was to expire in 2022. In light of the U.S. marketing approval of Ocaliva for PBC in May 2016, the company applied for an extension of the patent term for this patent in the United States into 2027, which extension has been granted. In February 2022, the company filed a terminal disclaimer in the United States Patent and Trademark Office concerning the company’s primary composition of matter patent for OCA, which changed the expiration date of the patent from November 16, 2027 to February 21, 2027. The issued patents covering OCA are expected to expire in 2027 at the earliest and 2036 at the latest if the appropriate maintenance, renewal, annuity, or other government fees are paid. The company has received paragraph IV certification notice letters from seven generic drug manufacturers indicating that each such manufacturer submitted to the FDA an ANDA seeking approval to manufacture and sell a generic version of the company’s 5 mg and 10 mg dosage strengths of Ocaliva for PBC prior to the expiration of certain patents listed for Ocaliva in the Orange Book. The seven generic drug manufacturers and when the company received their initial paragraph IV certification notices are as follows: (1) Apotex Inc. (‘Apotex’) (July 2020), (2) Lupin Limited (‘Lupin’) (July 2020), (3) Amneal Pharmaceuticals of New York, LLC, as U.S. agent for Amneal EU Limited (collectively, ‘Amneal’) (July 2020), (4) Optimus Pharma Pvt Ltd (‘Optimus’) (July 2020), (5) MSN Pharmaceuticals Inc. and MSN Laboratories Private Limited (collectively, ‘MSN’) (July 2020), (6) Dr. Reddy’s Laboratories, Inc., and Dr. Reddy’s Laboratories, Ltd. (collectively, ‘Dr. Reddy’s’) (December 2020), and (7) Zenara Pharma Private Limited (‘Zenara’) (August 2022). Each paragraph IV certification notice alleged that the challenged Orange Book patents were invalid, unenforceable, and/or would not be infringed by the commercial manufacture, use, or sale of the generic products described in the generic manufacturer’s respective ANDA. In each case, within 45 days of receipt of the paragraph IV certification notice, the company initiated a patent infringement suit against the generic manufacturer in the United States District Court for the District of Delaware. The company entered into settlement agreements with Apotex, Lupin, Amneal, Optimus, MSN and Dr. Reddy’s. Those settlements fully resolved the patent infringement case in the United States District Court for the District of Delaware that was scheduled for trial on February 27, 2023, and the case was terminated by the Court. Separate patent litigation against Zenara remains pending in the District of Delaware, with trial scheduled for July 22, 2024. Under the Drug Price Competition and Patent Term Restoration Act of 1984 (the ‘Hatch-Waxman Act’), the FDA cannot grant final approval of the Zenara ANDA before the earlier of February 8, 2025, or a court decision in its favor. Under the terms of the six settlement agreements, the company granted each of the manufacturers a non-exclusive, non-sublicensable, non-transferable, royalty-free license to commercialize a generic version of Ocaliva in the United States commencing on a specified date, or earlier under certain circumstances. The earliest such specified date agreed to is September 1, 2031 (for Apotex). Trademarks The Intercept Pharmaceuticals name and logo and the Ocaliva name and logo are either registered or unregistered trademarks or trade names of the company in the United States and/or other countries. Sales and Marketing Ocaliva is the company’s first approved product and the commercial launch of Ocaliva for PBC was the company’s first product launch. The company is commercializing Ocaliva for PBC using a combination of its internal commercial organization and third-party distributors. The company is developing its commercialization strategy for OCA for liver fibrosis due to NASH, if approved, and have not yet decided on the company’s commercialization strategy for OCA for other indications or for its other product candidates, in each case, if approved. The company intends to continue to evaluate how best to commercialize the company’s product candidates, if approved, and may choose to collaborate with third parties that have sales and marketing capabilities and established distribution systems, either to augment the company’s own capabilities or in lieu thereof. Customers The company commenced its commercial launch of Ocaliva for the treatment of PBC in the United States in June 2016. In December 2016, the European Commission granted conditional approval for Ocaliva for the treatment of PBC. Since January 2017, Ocaliva has also received regulatory approval in several markets outside the United States and Europe, including (but not limited to) Canada, Israel and Australia. The company sells Ocaliva to a limited number of specialty pharmacies, which dispense the product directly to patients. The specialty pharmacies are referred to as the company’s customers. Government Regulation and Product Approval The company’s product candidates must be approved by the FDA through the NDA process before they may be legally marketed in the United States and, if applicable, by the European Commission following a favorable assessment provided by the EMA through the MAA process for a product falling within the scope of the Centralized procedure or a national MAA process (albeit through the process of Mutual Recognition or Decentralized procedure) before they may be legally marketed in the European Union. The company and its third-party manufacturers are required to ensure that all of the company’s processes, methods, and equipment are compliant with cGMP. The company is also required as a condition of Medicaid participation to discount the company’s products to authorized users of the Federal Supply Schedule of the General Services Administration, including the TRICARE retail pharmacy program, under which additional laws and requirements apply. Research and Development The company’s research and development expenses were $176.6 million for the year ended December 31, 2022. History Intercept Pharmaceuticals, Inc. was founded in 2002. The company was incorporated in the state of Delaware in 2002.