Eiger BioPharmaceuticals Stock

Eiger BioPharmaceuticals, Inc. (Eiger), a commercial-stage biopharmaceutical company, focuses on the development and commercialization of foundational therapies for hepatitis delta virus (HDV) infection.

Clinical Product Candidates

Lonafarnib (LNF) for HDV

LNF is a well-characterized, orally bioavailable, first-in-class farnesylation inhibitor in a Phase 3 clinical trial for HDV infection and is the company’s lead program. HDV is the most severe form of viral hepatitis for which there is no FDA-approved therapy.

The company licensed LNF from Merck in 2010. LNF is a small molecule that blocks the production of HDV virus particles by inhibiting a key step, called farnesylation, in the virus life cycle. The company has completed five Phase 2 dose-finding studies in 129 HDV-infected patients. LNF has demonstrated dose-dependent activity in reducing HDV viral load both as a monotherapy and in combination with ritonavir (RTV) and/or PEG IFN-alfa-2a. Phase 2 studies have identified two lonafarnib-based regimens, which are in the company’s Phase 3 registration program. Both regimens have achieved clinically meaningful composite endpoints of HDV RNA decline = 2 logs from baseline and normalized alanine aminotransferase (ALT), a key liver enzyme, at Week 24: all-oral regimen of LNF 50 mg boosted with RTV twice daily and combination regimen of LNF boosted with RTV combined with PEG IFN-alfa-2a. Predominantly grade 1 gastrointestinal (GI) adverse events (AE) were observed in Phase 2 amongst per-protocol treated patients.

The company’s Phase 3 registration program consists of a single, pivotal, international trial, called D-LIVR, that is designed to support the U.S. and the European Union regulatory approvals. D-LIVR has the potential to generate data for two distinct lonafarnib-based ritonavir-boosted regimens for approval. The study includes an all-oral arm of lonafarnib boosted with ritonavir and a combination arm of lonafarnib boosted with ritonavir combined with peginterferon-alfa-2a. Each arm is compared to placebo. Topline Week 48 data announced in December 2022 demonstrated that both lonafarnib-based regimens showed statistical significance versus placebo on the primary endpoint. Week 72 data is expected in mid-2023.

LNF for the treatment of HDV infection has been granted Orphan Drug designation by the FDA and European Medicines Agency (EMA), Fast Track and Breakthrough Therapy designations by the U.S. Food and Drug Administration (FDA) and PRIME designation by the EMA.

Peginterferon Lambda (lambda) for HDV

Lambda is the company’s second program in clinical development for HDV and is in Phase 3. Lambda is a well-characterized, first-in-class, type III, well-tolerated interferon (IFN), that stimulates immune responses that are critical for the development of host protection during viral infections.

The company licensed worldwide rights to lambda from Bristol Myers Squibb in April 2016. Lambda has been administered in clinical trials involving over 4,000 patients infected with the Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), and SARS-CoV-2. Lambda has not been approved for any indication.

The company previously completed the Phase 2 LIMT-1 study of 33 HDV-infected patients. Based on the data from LIMT-1, it has agreement with the FDA and EMA on a single pivotal, randomized Phase 3 open-label study, called LIMT-2, of lambda as a monotherapy for the treatment of HDV. The primary endpoint, as achieved in Phase 2, is a durable virologic response (DVR), defined as HDV ribonucleic acid (RNA) below the limit of quantitation (BLQ) at 24-weeks post-treatment. LIMT-2 is enrolling and dosing patients across approximately fifty clinical trial sites in thirteen countries with a target enrollment of 150 patients in by mid-2023.

Lambda for the treatment of HDV infection has received Orphan Drug designation from the FDA and the EMA and Fast Track and Breakthrough Therapy designations from the FDA.

Combination Therapy for HDV

The company has also generated data with the combination of LNF + RTV and lambda for the treatment of HDV. The Phase 2 LIFT-1 study was a single arm investigator sponsored study of lambda combined with LNF boosted with RTV for 24 weeks treatment with 24 weeks follow-up. In November 2020, the company reported positive end-of-study data from a Phase 2 single arm study called LIFT-1, conducted at the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 26 HDV-infected patients.

The Phase 2 LIFT-2 single arm study of 48 weeks treatment with lambda combined with LNF boosted with RTV is planned to initiate in 2023 with an enrollment target of 30 HDV-infected patients. The primary endpoint is a DVR.

Peginterferon Lambda (lambda) for COVID-19

The company has also generated data with lambda in multiple Phase 2 and Phase 3 investigator sponsored studies of mild and moderate COVID-19 patients.

The TOGETHER study was an investigator sponsored Phase 3, multi-center, randomized, placebo-controlled adaptive platform study evaluating therapeutics in newly diagnosed, high-risk, non-hospitalized patients with COVID-19 across twelve clinical trial sites in Brazil and 5 sites in Canada.

The company submitted a pre-EUA meeting request to the FDA, as well as additional morbidity and mortality outcomes data and analyses from the investigator-sponsored TOGETHER study. In response, the FDA denied the request for a pre-EUA meeting. Citing its concerns with the conduct of the TOGETHER study, the FDA concluded that any authorization request based on these data is unlikely to meet the statutory criteria for issuance of an Emergency Use Authorization (EUA) in the context of the pandemic.

The FDA suggested that, given lambda's mechanism of action and the ongoing need for improved COVID-19 therapeutics, the company should consider requesting an end-of-Phase 2 meeting to discuss a company-sponsored pivotal trial that could support an eventual Biologics License Application (BLA). The company continues to explore opportunities for ex-U.S. emergency use of lambda for COVID-19 and other respiratory viral infections.

Avexitide in Congenital Hyperinsulinism (HI)

Avexitide is a well-characterized peptide that the company is developing as a treatment for congenital hyperinsulinism (HI), an ultra-rare, pediatric metabolic disorder. Avexitide has demonstrated clinical proof of concept and has been dosed in over 25 patients with HI at Children’s Hospital of Philadelphia (CHOP).

Avexitide has been granted Breakthrough Therapy designation by the FDA for the treatment of HI, Orphan Drug designation by the EMA for the treatment of HI and Orphan Drug designation by the FDA for the treatment of hyperinsulinemic hypoglycemia, which includes HI. Avexitide has also been granted Rare Pediatric Disease designation by the FDA.

Avexitide in Post-Bariatric Hypoglycemia (PBH)

The company is also developing avexitide as a treatment for post-bariatric hypoglycemia (PBH), a debilitating and potentially life-threatening condition for which there is no approved therapy.

Five clinical studies have been completed demonstrating clinical proof of concept in over 70 patients suffering from PBH indicating that avexitide can reduce hypoglycemia and associated symptoms in affected patients. Avexitide is a glucagon-like peptide-1 (GLP-1) receptor antagonist that competes with endogenous Glucagon Like Peptide-1 (GLP-1) and has been shown to reduce the excessive post-prandial insulin release that characterizes this disorder. These Phase 2 data were generated using intravenous or subcutaneous (SC) formulation delivery. Pharmacokinetics from these Phase 2 SC studies indicate that the SC formulation could enable once or twice a day dosing. The company developed a proprietary SC liquid formulation and completed a Phase 1 dose-ranging pharmacokinetics trial in healthy humans.

Avexitide for the treatment of hyperinsulinemic hypoglycemia has been granted Orphan Drug designation by the FDA and for the treatment of non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) by the EMA. NIPHS describes a spectrum of acquired metabolic disorders characterized by inappropriately high insulin levels (hyperinsulinemia) and low blood glucose levels (hypoglycemia), which includes PBH. Avexitide for the treatment of PBH has also been granted Breakthrough Therapy designation by the FDA. Following End of Phase 2 and Scientific Advice meetings with regulatory agencies, the company has agreement on a single pivotal Phase 3 study.

Approved Product

Zokinvy (lonafarnib) for Hutchinson-Gilford progeria syndrome (HGPS) and Processing-Deficient Progeroid Laminopathies (PL)

In November 2020, the company received FDA approval for Zokinvy to reduce the risk of mortality in HGPS and to treat processing-deficient PL. Collectively known as progeria, these are ultra-rare and rapidly fatal genetic conditions of accelerated aging in children. Zokinvy is the company’s first approved product, and the first approved therapy for these indications. There are approximately 20 identified patients in the U.S. who are eligible for treatment with Zokinvy.

In July 2022, the company announced that the European Commission (EC) granted Eiger a centralized marketing authorization (MA) under the exceptional circumstances procedure for Zokinvy for the treatment of HGPS and PL, ultra-rare and rapidly fatal genetic conditions of accelerated aging in children. In July 2022, the company announced that the European Commission (EC) granted Eiger a centralized marketing authorization (MA). The EC's centralized MA is valid in all 27 European Union member states plus Iceland, Liechtenstein, and Norway. In August 2022, the Medicine and Healthcare products Regulatory Agency (MHRA) granted approval in the U.K.

Zokinvy is a disease-modifying agent that has demonstrated a statistically significant survival benefit in children and young adults with HGPS. In patients with HGPS, Zokinvy reduced the incidence of mortality by 60% (p=0.0064) and increased average survival time by at least 2.5 years. Many patients with HGPS have received continuous Zokinvy therapy for more than 10 years.

In November 2020, the company entered into an amendment to its license agreement with Merck to include not only all uses of LNF related to the treatment of HGPS, but also progeroid laminopathies.

Strategy

The company’s strategy is to identify, develop, and, directly or through collaborations, bring to market novel products for the treatment of rare and ultra-rare diseases or conditions.

Intellectual Property

Patent Protection of Product Candidates

LNF

The company has licensed from Merck a portfolio of patents and know how covering the compound, formulations of the compound, and synthesis, but these expire before the anticipated launch date of the LNF product candidate.

In the United States, the company has obtained patent protection for the use of LNF in combination with RTV for the treatment of HDV infection. Eiger’s U.S. Patent Nos. 10,076,512; 10,828,283; and 11,311,519 entitled, Treatment of Hepatitis Delta Virus Infection, include claims covering a broad range of RTV-boosted LNF doses and durations with and without interferons. The patents have terms that extend at least until 2035. Additional claims are being pursued in a continuation application. The European Patent Office, the Chinese Patent office and the Japanese Patent Office have also granted patents with claims covering a broad range of LNF boosted with RTV dosing regimens for the treatment of HDV infection. These patents will have a term that extends to 2035. In Europe, China and Japan, additional claims are being pursued in divisional applications. The company has obtained patent protection with claims covering treatment of HDV with LNF boosted with RTV the U.S., Europe, China and Japan, which are key major pharmaceutical markets. A corresponding patent application claiming the use of lonafarnib boosted with ritonavir is pending in Korea. Additionally, U.S. Patent 10,835,496 and European Patent issued claiming particular dosage forms for ritonavir-boosted lonafarnib for the treatment of HDV infections. A Notice of Allowance was also received for an application in South Korea. These patents extend protection until at least 2036.

The company has in-licensed from The Progeria Research Foundation patents covering the methods of treating Hutchinson-Gilford progeria syndrome (HGPS), and progeroid laminopathies. The patents provide protection until at least 2024 and an application for patent term extension (PTE) that could extend the protection for one of the patents until 2029 has been filed. The company has also filed a patent application in the U.S. directed to methods of treating HGPS and progeroid laminopathies that if issued would provide further protection until at least 2039. In addition, LNF has been granted Orphan Drug designation by the FDA and the EMA in this indication, which respectively may provide up to seven and ten years of regulatory exclusivity.

Lambda

The company has in-licensed from BMS a portfolio of patents relating to the manufacture, use, and compositions of interferon lambda modified by polyethylene glycol derivatization (lambda). The key United States composition of matter patent in this portfolio expires in 2025, but the company expects to be eligible for the full five years of patent term extension for that patent. In addition, the company expects regulatory approval for lambda to be filed under a BLA, which if granted would provide 12 years reference product exclusivity (4 years in filing exclusivity; 12 years for data), as well as Orphan Drug exclusivity for the treatment of HDV infection.

In the United States and Europe, the company has obtained patent protection for the use of lambda for the treatment of HDV infection. U.S. Patent No. 10,953,072 issued with claims covering the use of lambda to treat HDV. The term of this patent extends at least until 2037. The European Patent Office has also granted a patent with claims covering use of lambda to treat HDV. Additional claims are being pursued in continuation/divisional applications in the U.S. and Europe. Applications are also pending in China, Japan and Korea. Any patents that issue from these applications will expire in 2037.

The company also filed a PCT application relating to the use of lambda in HDV that has matured into patent applications in the United States, Europe, Australia, Brazil, Canada, China, Eurasia, Israel, India, Japan, South Korea, Mexico, and South Africa. Any patents that issue from these applications should offer protection until at least 2039.

In addition, the company has filed a PCT application related to the use of lambda and lonafarnib and ritonavir to treat HDV, that has matured into patent applications in the United States, Europe, Australia, Brazil, Canada, China, Israel, Japan, South Korea, Mexico, Russia, Ukraine, and South Africa. Any patents that issue from these applications should offer protection until at least 2040. Lastly, the company also filed a PCT application related to the use of lambda to treat COVID-19 that has matured into patent applications in the United States, Europe, Australia, Brazil, Canada, Chile, China, Columbia, Eurasia, Israel, Japan, South Korea, Mexico, New Zealand, Saudi Arabia, Singapore, Ukraine, Vietnam, and South Africa.

Avexitide

The company has in-licensed from Stanford two PCT applications that claim the use of avexitide and other agents in the treatment of hypoglycemia associated with bariatric surgery, including in PBH. The United States Patent and Trademark Office (USPTO) issued US 10,639,354, US 10,660,937, US 10,993,992, and US 10,993,991, which provide protection at least until 2036. Up to five years of patent term extension will be available in the United States. The European Patent Office has also granted two patents with claims covering use of avexitide to treat hypoglycemia, which will expire in 2036. Two Australian patents and a Chilean patent have also issued with similar claims, which will also expire in 2036 Additional claims are being pursued in continuation/divisional applications in the U.S. and Europe. Applications are also pending in Canada, and Chile. Any patents that issue from these applications will expire in 2036. Additionally, avexitide has been granted Orphan Drug designation in the treatment of hyperinsulinemic hypoglycemia by the FDA and the EMA, which provides seven years and ten years of regulatory exclusivity in the United States and Europe, respectively.

In the United States, the company has obtained patent protection for formulations of avexitide and the use of these formulations in the treatment of hypoglycemia associated with bariatric surgery. The USPTO issued US 11,020,484, which will provide protection at least until 2037. Additional claims are being pursued in continuation application. Applications are also pending in Europe, Australia, Brazil, Canada, Chile, China, Hong Kong, Israel, India, and Japan. Any patents that issue from these applications will expire in 2037.

The company has also filed a PCT (Patent Cooperation Treaty of 1970) application related to method of treating HI and PBH, that has matured into patent applications in the United States, Australia, Brazil, Canada, Chile, China, Europe, Israel, and Japan. If issued, the patents will provide protection until 2039. The company has also filed a PCT application related to method of treating congenital hyperinsulinism, which will offer protection until 2042 if issued into patents at the national stage.

The company has in-licensed patents and patent applications from the Trustees of the University of Pennsylvania (UPenn) and Children's Hospital of Philadelphia (CHOP), relating to hyperinsulinemia hypoglycemia. The in-licensed patents and applications relate to multiple hyperinsulinemic disorders, including PBH and HI. The patents, which are issued in the U.S. and Europe, provide protection until 2028. There are continuation applications pending from which the company is pursuing additional claim coverage.

License Agreements

License Agreement with Merck

In September 2010, the company entered into an exclusive license agreement with Schering Corporation, subsequently acquired by Merck, which provides the company with the exclusive right to develop and commercialize lonafarnib.

In May 2018, the company entered into an amendment to the exclusive license agreement with Merck & Co., Inc. (Merck), which provides for expansion of the existing exclusively licensed field of use under the license agreement with Merck to include all uses of lonafarnib related to the treatment of Hutchinson-Gilford progeria syndrome (HGPS) in humans to the company. It has the sole responsibility and the continuing obligation for the manufacture and supply of lonafarnib to The Progeria Research Foundation.

In November 2020, the company entered into an amendment to the exclusive license agreement with Merck which expanded the definition of HGPS to also include progeroid laminopathies.

License Agreement with Bristol-Myers Squibb Company

In April 2016, the company entered into a License Agreement and a Common Stock Purchase Agreement with Bristol-Myers Squibb Company (BMS). Under the BMS License Agreement, BMS granted the company an exclusive, worldwide, license to research, develop, manufacture, and sell products containing the proprietary BMS molecule known as PEG-interferon Lambda-1a (peginterferon lambda or the Licensed Product) for all therapeutic and diagnostic uses in humans and animals. The company is responsible for the development and commercialization of the Licensed Product.

License Agreement with the Trustees of the UPenn and CHOP

In May 2019, the company entered into a license agreement (the UPenn/CHOP Agreement) with the Trustees of the University of Pennsylvania (UPenn) and the Children’s Hospital of Philadelphia (CHOP), under which it obtained an exclusive, royalty-bearing, worldwide license to develop, manufacture and sell certain GLP-1 receptor antagonist(s) products to treat all human and animal conditions. The company also obtained an exclusive, royalty-bearing, sublicensable, worldwide license to certain data developed by CHOP. The company is responsible for the development and commercialization of the licensed products.

Research and Development

The company’s research and development expenses were $75.3 million for the year ended December 31, 2022.

Government Regulations and Product Approvals

All of the company’s product candidates are subject to regulation in the United States by the FDA under the Federal Food, Drug, and Cosmetic Act (FDC Act) and its implementing regulations. The company’s lambda product candidate is additionally subject to regulation as a biologic under the Public Health Service Act.

In the United States, the company’s activities are subject to regulation by federal, state, and local authorities in addition to the FDA. These other agencies include, without limitation, the Centers for Medicare and Medicaid Services, the Office of Inspector General for the U.S. Department of Health and Human Services, other divisions of the U.S. Department of Health and Human Services, the U.S. Department of Justice and individual U.S. Attorney offices within the Department of Justice, as well as state and local governments. Such agencies enforce a variety of laws, including without limitation, anti-kickback and false claims laws, data privacy and security laws, drug price reporting laws, and physician payment transparency laws.

History

Eiger BioPharmaceuticals, Inc. was founded in 2008. The company was incorporated in the state of Delaware in 2008.