Arena Pharmaceuticals, Inc. operates as a biopharmaceutical company. The company focuses on delivering novel, transformational medicines with optimized pharmacology and pharmacokinetics to patients globally.
The company’s internally developed pipeline includes multiple potentially first- or best-in-class assets with broad clinical utility. The company’s most advanced investigational clinical programs include:
Etrasimod, which it is evaluating in a Phase 3 program for ulcerative colitis (UC), a...
Arena Pharmaceuticals, Inc. operates as a biopharmaceutical company. The company focuses on delivering novel, transformational medicines with optimized pharmacology and pharmacokinetics to patients globally.
The company’s internally developed pipeline includes multiple potentially first- or best-in-class assets with broad clinical utility. The company’s most advanced investigational clinical programs include:
Etrasimod, which it is evaluating in a Phase 3 program for ulcerative colitis (UC), a Phase 2b/3 program for Crohn’s disease, or CD, a Phase 2 program in alopecia areata, or AA, and a Phase 2b program for eosinophilic esophagitis, or EoE. The company also plans to evaluate etrasimod in a Phase 3 program in atopic dermatitis, or AD.
APD418, for acute heart failure, or AHF, which the company is evaluating in a Phase 2 trial.
Temanogrel, a second compound in the company’s cardiovascular therapeutic area, which it is evaluating in a Phase 2 trial for microvascular obstruction, or MVO, and a Phase 2 trial for Raynaud’s phenomenon secondary to systemic sclerosis, or SSc-RP.
Olorinab, which the company is evaluating for a broad range of visceral pain conditions associated with gastrointestinal diseases. The company is evaluating possible strategic options for olorinab.
The company continues to leverage its two decades of world-class G-protein-coupled receptor, or GPCR, target discovery research to develop breakthrough drugs and ultimately deliver these to patients with unmet needs. The company’s long-term pipeline prospects include a collaboration with Beacon Discovery, Inc., or Beacon, across a broad range of immune-mediated inflammatory targets and compounds.
The company has license agreements or collaborations with various companies, including United Therapeutics (ralinepag in a Phase 3 program for pulmonary arterial hypertension); Everest Medicines Limited (etrasimod in a Phase 3 program for UC in Greater China and select countries in Asia); Beacon Discovery (early research platform for G-protein-coupled receptor (GPCR) targets); Boehringer Ingelheim International GmbH (undisclosed orphan GPCR program for central nervous system – preclinical); and Aristea Therapeutics, Inc. (RIST4721 in a Phase 2 program for the treatment of palmoplantar pustulosis and other neutrophil-mediated diseases).
Etrasimod is a next-generation, oral, highly selective sphingosine 1-phosphate, or S1P, receptor modulator, discovered by the company, designed to provide systemic and local cell modulation by selectively targeting S1P receptor subtypes 1, 4 and 5. S1P receptors have been demonstrated to be involved in the modulation of several biological responses, including lymphocyte trafficking from lymph nodes to the peripheral blood. By isolating subpopulations of lymphocytes in lymph nodes, fewer immune cells are available in the circulating blood to effect tissue damage. Etrasimod has therapeutic potential in immune-mediated inflammatory disease areas including gastroenterology and dermatology. The company is evaluating etrasimod in ulcerative colitis, Crohn’s disease, eosinophilic esophagitis, atopic dermatitis, and alopecia areata. The company is in a Phase 3 program in UC and a Phase 2b/3 program in CD.
ELEVATE UC constitutes the company’s Phase 3 global registrational program to assess the safety and efficacy of once-daily etrasimod 2 mg in participants with moderately to severely active UC. In January 2021, the pivotal, 52-week ELEVATE UC 52 trial completed enrollment. In August 2021, the pivotal, 12-week ELEVATE UC 12 trial reached full enrollment. The company expects topline data from both ELEVATE UC 12 and ELEVATE UC 52 in the first quarter of 2022.
In April 2021, the company enrolled the first patient in a Phase 2 trial evaluating etrasimod for the potential treatment of moderately active UC, called GLADIATOR UC. This trial is a multicenter, randomized, placebo-controlled 52-week trial to assess the safety and efficacy of once-daily etrasimod 2 mg in participants with moderately active UC. This trial is intended to evaluate etrasimod in a less severe patient population than ELEVATE UC, potentially broadening the patient population and demonstrating the potential use of a once-a-day oral therapy earlier in the treatment paradigm.
The company is recruiting for a Phase 2b program for EoE. In February 2021, the company dosed the first participant in the Phase 2b VOYAGE trial for etrasimod in EoE. The company’s Phase 2b VOYAGE trial of etrasimod is a randomized, double-blind, placebo-controlled trial, with a primary efficacy measurement at week 16 and a secondary efficacy analysis at week 24, to assess the safety and efficacy of 1 mg and 2 mg etrasimod in approximately 100 adult participants with EoE. In June 2021, the FDA granted Orphan Drug Designation status to etrasimod for the treatment of EoE.
The company is in planning for a Phase 3 program for AD and has ongoing discussions with regulatory authorities on trial design. In July 2021, the company evaluated an updated open-label extension data set from the Phase 2 ADVISE trial for 2 mg etrasimod in atopic dermatitis that demonstrated meaningful effects at week 16 of the open-label extension (OLE) period on validated Investigator Global Assessment, or vIGA, at 47%, Eczema Area and Severity Index, or EASI-75, at 72%, and Peak Pruritis Numeric Rating Scale, or PP-NRS, at 61% with consistent safety profile out to one year.
The company is recruiting a Phase 2 program in Alopecia Areata. In July 2021, the Phase 2 trial for etrasimod in AA was amended to add a 3 mg cohort and expand patient population subtypes. The Phase 2 randomized, placebo-controlled trial will assess the safety and efficacy of once-daily etrasimod 2 mg and 3 mg in 78 participants with moderate-to-severe AA. The company expects to announce topline data for this trial in the second half of 2022. In April 2020, the company announced data from a Phase 1 clinical trial evaluating a controlled-release delivery profile for etrasimod. As of February 4, 2022, the company owned issued patents that cover compositions of matter for etrasimod and related compounds, and methods of treatment utilizing etrasimod and related compounds, in 62 jurisdictions, including the United States, China, Japan, Germany, France, Italy, the United Kingdom, Brazil, Spain, Canada, India, Russia, South Korea and Australia. The earliest priority date for the patents on etrasimod is 2008. The terms of these patents are capable of continuing into 2029 in most jurisdictions without taking into account any patent term adjustment or extension regimes of any country or any additional term of exclusivity the company might obtain by virtue of the later filed patent applications.
APD418 is a potential first-in-class ß3-adrenergic receptor (AdrR) antagonist and cardiac myotrope designed to regulate myofilament calcium sensitivity in order to improve contractility without inducing the serious adverse events associated with available inotropes. APD418 is in early-stage clinical development for patients with AHF. AHF is broadly defined as a rapid onset of new or worsening signs and symptoms of HF.
In July 2021, the company announced that a Phase 2 trial for APD418 was initiated. The randomized, double-blind, placebo-controlled trial is intended to evaluate the safety, pharmacokinetics, and effect on cardiac function of intravenous APD418 in approximately 80 adult participants with heart failure with reduced ejection fraction.
In November 2020, the company announced the completion of a first-in-human Phase 1 safety and tolerability trial of APD418. The trial found APD418 was generally well tolerated.
The FDA has granted the company Fast Track designation for the development of APD418 in AHF.
As of February 4, 2022, the company owned issued patents covering compositions of matter for APD418 and related compounds, and methods of treatment utilizing APD418 and related compounds, in the United States, Japan, Australia, and three other jurisdictions, and the company had applications pending in 37 other jurisdictions, of which the ones with the largest pharmaceutical markets were Europe and China. The earliest priority date for the patents on APD418 is 2016. The terms of these patents are capable of continuing into 2037 without taking into account any patent term extension.
Temanogrel is a peripherally acting and selective 5HT2a inverse agonist designed to inhibit serotonin (5-HT)-mediated amplification of platelet aggregation and vasoconstriction.
The company is recruiting for a Phase 2b program for MVO.
In June 2021, the first participant was randomized in the Phase 2 trial for temanogrel in MVO. The randomized, double-blind, placebo-controlled trial is intended to evaluate the safety and effect on MVO of intravenous temanogrel in approximately 99 adult participants undergoing percutaneous coronary intervention.
The FDA has granted the company Fast Track designation for the development of temanogrel for MVO.
The company is recruiting for a Phase 2b program for SSc-RP.
In November 2021, the first participant was randomized in the Phase 2 trial for temanogrel in SSc-RP. The randomized, double-blind, placebo-controlled, crossover trial is intended to evaluate the safety and effect of oral temanogrel on digital blood flow in approximately 48 participants with SSc-RP.
The company has completed four Phase 1 studies with the oral formulation and one Phase 1 study with the IV formulation of temanogrel.
As of February 4, 2022, the company owned issued patents that cover compositions of matter for temanogrel and related compounds, and methods of treatment utilizing temanogrel and related compounds, in 9 jurisdictions, including the United States, Japan, Germany, France, Italy, the United Kingdom, and Spain. The earliest priority date for the patents on temanogrel is 2004. The terms of these patents are capable of continuing into 2025 in most jurisdictions without taking into account any patent term adjustment or extension regimes of any country or any additional term of exclusivity the company might obtain by virtue of the later filed patent applications.
In March 2021, the company announced topline results from the CAPTIVATE trial for the treatment of abdominal pain associated with irritable bowel syndrome and showed that although olorinab was well tolerated it did not meet the primary efficacy endpoint of statistically significant improvement in the overall AAPS from baseline to week 12. CAPTIVATE was a Phase 2, 4-arm multi-center, randomized, double-blind, placebo-controlled, 12-week trial to assess the safety and efficacy of olorinab administered three times daily in 273 participants.
As of February 4, 2022, the company owned issued patents covering compositions of matter for olorinab and related compounds, and methods of treatment utilizing olorinab and related compounds, in 23 jurisdictions, including the United States, China, Japan, Canada, India, Russia, South Korea and Australia, and the company had applications pending in 8 other jurisdictions, of which the ones with the largest pharmaceutical markets were Europe, Venezuela, and Brazil. The earliest priority date for the patents on olorinab is 2009. The terms of these patents are capable of continuing into 2030 in most jurisdictions without taking into account any patent term adjustment or extension regimes of any country or any additional term of exclusivity the company might obtain by virtue of the later filed patent applications.
In January 2020, the company entered an agreement with Beacon Discovery for the development of multiple novel, early stage, oral autoimmune programs. The multiple G-protein-coupled receptor, or GPCR, targets in this collaboration with Beacon Discovery and their associated chemistry represent the next generation of oral compounds which, if successfully developed and approved, may transform the way autoimmune diseases are approached and treated. This collaboration includes both novel and validated targets and compounds.
The company has additional assets, including other 5-HT2A modulators, which are either in or being evaluated for future clinical and preclinical development. The company is also evaluating additional delivery forms of the products in its pipeline to extend clinical utility or improve the product profile.
Strategy
The primary elements of the company’s strategy are to develop etrasimod – a modulator of the sphingosine 1-phosphate, or S1P, receptor intended for the treatment of a broad range of immune-mediated inflammatory diseases including gastrointestinal and dermatologic diseases; evaluate possible strategic options for olorinab – an agonist of the cannabinoid receptor 2, or CB2, intended for the treatment of a range of visceral pain associated with gastrointestinal conditions; develop APD418 – a ß3-AdrR antagonist and cardiac myotrope intended for AHF; develop temanogrel – a peripherally acting and selective 5HT2a inverse agonist intended for MVO and SSc-RP; progress a broad early-stage pipeline build with Beacon; consider other external opportunities with potential for transformational innovation in the company’s disease areas of interest; develop the company’s pipeline by efficiently managing its cash and development timelines, which may include entering strategic agreements for certain clinical and preclinical programs; explore existing compounds in new indications and progress additional pipeline programs over time in select therapeutic areas; and prudently build a vibrant, sustainable, high-performing organization.
Collaborations and License Agreements
The company has strategic collaborations and licenses with pharmaceutical companies, including United Therapeutics Corporation (United Therapeutics); Everest Medicines Limited (Everest); Boehringer Ingelheim International GmbH (Boehringer Ingelheim); Beacon; Eisai Co., Ltd. and Eisai Inc. (collectively, Eisai); and Aristea Therapeutics, Inc. (Aristea).
Aristea Collaboration and Option Agreement
In July 2021, the company entered into a strategic collaboration and option agreement to advance the clinical development of RIST4721, an oral CXCR2 antagonist being developed by Aristea for the treatment of palmoplantar pustulosis (PPP) and other neutrophil-mediated diseases.
United Therapeutics License Agreement
In November 2018, the company entered into a collaboration and license agreement with United Therapeutics. Under the United Therapeutics Agreement, the company granted United Therapeutics an exclusive, worldwide, royalty-bearing license to develop, manufacture and commercialize ralinepag. This transaction was completed in January 2019. At the closing of the transaction, the company transferred to United Therapeutics certain other assets relating to ralinepag, including, among others, related domain names and trademarks, permits, certain contracts, inventory, regulatory documentation, Investigational New Drug (IND), and non-clinical, pre-clinical and clinical trial data. United Therapeutics has agreed to assume certain limited liabilities, including among others, all post-closing obligations under assumed contracts and the IND. United Therapeutics is responsible for all development, manufacture and commercialization of the licensed products globally.
Ralinepag Program
Ralinepag is in a Phase 3 program for pulmonary arterial hypertension, or PAH. Ralinepag is a next-generation potent, highly selective oral IP receptor agonist intended for the treatment of PAH. Ralinepag was designed by the company to deliver intravenous prostacyclin-like potency and pharmacokinetics in an oral tablet. In non-clinical experiments, ralinepag demonstrated potentially best-in-class activation of the IP receptor resulting in vasodilation, inhibition of smooth muscle cell proliferation and inhibition of platelet aggregation. Additionally, early-stage studies of ralinepag pharmacokinetics in humans revealed an approximately 24-hour half-life and a low peak-to-trough ratio supporting therapeutic blood levels with once daily dosing.
Ralinepag was granted orphan drug status for the treatment of PAH by the U.S. Food and Drug Administration, or FDA, in September 2014, and by the European Medicines Agency in January 2019.
Everest Collaboration
In December 2017, the company entered into a Collaboration and License Agreement, or the Everest Agreement, with Everest regarding the development and commercialization of ralinepag and etrasimod in China, Taiwan, Hong Kong, Macau and South Korea, or the Everest Territories. In January 2019, the company and Everest amended the Everest Agreement by entering into two separate agreements, one for each of ralinepag and etrasimod, with the terms for each program that are substantially the same as in the original Everest Agreement. Under the United Therapeutics Agreement, the company assigned the separate Everest Agreement related to ralinepag to United Therapeutics.
Under the separate Everest Agreement related to etrasimod, the company granted Everest an exclusive, royalty-bearing license to develop, manufacture and commercialize etrasimod (in oral formulations only), in the Everest Territories.
Everest is responsible for all development, manufacture and commercialization of the licensed products in the Everest Territories, and may participate in the portion of the company’s global clinical trials that is conducted in the Everest Territories.
The company is eligible to receive development, regulatory and commercial milestone payments from Everest, as well as tiered royalties on net sales ranging from the high single digits to low double digits. Following an initial royalty term, the company is eligible to receive a lower trademark royalty if Everest continues to use its licensed product-related trademarks.
In the fourth quarter of 2018, the National Medical Products Administration of China, accepted the initial clinical trial applications for an oral formulation of ralinepag and for etrasimod. Subsequently, in the fourth quarter of 2019, Everest announced that the first subject has been dosed in a Phase 3 trial evaluating etrasimod in development for the treatment of UC in Greater China and South Korea. This Phase 3 trial is ongoing.
Boehringer Ingelheim Collaboration
In 2015, the company entered into an exclusive agreement with Boehringer Ingelheim, to conduct joint research to identify drug candidates targeting a GPCR that belongs to a group of orphan central nervous system, or CNS, receptors. A lead molecule is in preclinical development.
Beacon Discovery Agreements
In January 2020, the company entered into a multi-year strategic Collaboration and License Agreement with Beacon, aimed at building novel medicines across a range of GPCR targets believed to play a role in immune and inflammatory diseases. Under the terms of this agreement, Beacon is responsible for early drug discovery activities and the company will be responsible for any potential future development and, ultimately, commercialization activities.
Beginning in September 2016, the company entered into a series of agreements with Beacon.
In 2016, the company entered into a License and Collaboration Agreement with Beacon, pursuant to which it granted Beacon a non-exclusive, non-assignable and non-sublicensable license to certain database information relating to compounds, receptors and pharmacology, and transferred certain equipment to Beacon. In 2016, the company also entered into a Master Services Agreement with Beacon, pursuant to which Beacon performs certain other research services for the company relating to its proprietary pipeline.
Research and Development
For the year ended December 31, 2021, the company’s research and development expenses included $419.5 million.
Service Marks
Arena Pharmaceuticals and Arena are registered service marks of the company.
Government Regulations
Drug manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic inspections (which may be unannounced) by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including Current Good Manufacturing Practices (cGMP) regulations, which impose certain procedural and documentation requirements upon the company and its third-party manufacturers.
The company is also subject to the U.S. Foreign Corrupt Practices Act, or the FCPA, which prohibits companies and individuals from engaging in specified activities to obtain or retain business or to influence a person working in an official capacity. The European General Data Protection Regulation, or GDPR, imposes many requirements and restrictions that impact its collection, transfer, use and retention of personal data of clinical trial subjects and other individuals in the European Union. For example, the GDPR dictates mandatory contractual terms for service providers that process personal data for the company and restricts its ability to transfer data from the European Economic Area to its offices and service providers in the United States and other countries. Penalties for non-compliance with the GDPR are steep, with potential fines of up to 4% of the company’s global revenue.
The company’s business involves the controlled use of hazardous materials, chemicals, biological materials and various radioactive compounds. In the United States, the company is subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the U.S. Environmental Protection Agency, the California Environmental Protection Agency, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, the Controlled Substances Act (CSA) and other federal, state or local regulations.
History
Arena Pharmaceuticals, Inc. was founded in 1997. The company was incorporated in the state of Delaware in 1997.
