Galmed Pharmaceuticals Stock

Galmed Pharmaceuticals Ltd. operates as a biopharmaceutical company.

The company focuses on the development of Aramchol. Historically, the company has focused almost exclusively on developing Aramchol for the treatment of liver disease. The company is also collaborating with the Hebrew University in the development of Amilo-5MER, a 5 amino acid synthetic peptide.

Aramchol is a synthetic conjugate of 3-amino cholic acid, or a type of modified bile acid, and arachidic acid, or a type of saturated fatty acid, which in its non-synthetic forms, is naturally occurring. The conjugated molecule acts upon important metabolic pathways, reducing fat accumulation in the liver, improving fatty acid oxidation and regulating the transport of cholesterol. Pre-clinical studies suggest Aramchol's effect on fibrosis is also direct via collagen production from human hepatic stellate cells.

In May 2022, the company announced its plan to expand into new anti-fibrotic indications to maximize the potential of Aramchol, while at the same time discontinuing the open label part of its ARMOR Study having reached its objectives. As a result of the cost reduction plan, the company discontinued any non-essential research and development activities and reduced its headcount by approximately 65% leaving a core team of management and research and development personnel. Following the discontinuation of the company's open label part of the ARMOR Study, it does not expect to initiate the second part of the ARMOR Study.

The company is exploring the feasibility of developing Aramchol for other indications outside of liver disease and anti-fibrotic indications and it continues to collaborate with the Hebrew University in the development of Amilo-5MER, however it has no plans to initiate a clinical trial for Aramchol or Amilo-5MER and is continuing to evaluate its strategic alternatives and its structuring.

Aramchol for Non-Alcoholic Steato-Hepatitis (NASH)

The company's product candidate, Aramchol, is a first-in-class synthetic fatty acid-bile acid conjugate molecule (FABAC), molecule that it is developing for oral treatment for NASH in patients who are overweight or obese and have prediabetes or type II diabetes mellitus.

Phase 1 Single and Multiple-Dose Study of Aramchol in Healthy Male Volunteers (NCT00776841)

Aramchol was evaluated in two Phase 1 clinical trials (under a single protocol) to study its safety, tolerability and pharmacokinetics (PK) profile in healthy volunteers, in both single and multiple dose administrations. The first Phase 1 clinical trial was an escalating single-dose trial conducted in 17 healthy subjects testing Aramchol doses ranging from 30 mg to 900 mg, performed in one center in Israel. The subsequent Phase 1 clinical trial was a repeated-dose trial conducted over four days in 25 healthy subjects testing repeated daily doses of Aramchol of 30 mg and 300 mg, performed in one center in Israel.

Phase 2a Trial: Aramchol Treatment in NAFLD or NASH Patients (NCT01094158)

The company completed a 60 patient multi-center, randomized, double-blind, placebo-controlled Phase 2a clinical trial of Aramchol in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) or NASH between the ages of 18 and 75 in 12 centers in Israel. The Phase 2a study results were published in the peer-reviewed Clinical Gastroenterology and Hepatology Journal. The trial was performed in patients with either NAFLD or NASH, which design was deemed acceptable by the U.S. Food and Drug Administration (FDA) in 2007 at a pre-IND scientific advisory meeting.

Pharmacokinetics of Single and Multiple Escalating Doses of Aramchol and Food Effect in Healthy Volunteers (NCT02374437)

The company commenced PK and food effect studies of Aramchol. In written correspondence regarding a requested pre-IND meeting, the FDA recommended that it conducts such studies prior to commencing its Phase 2b ARREST Study.

Pharmacokinetics of Single and Multiple Escalating Doses of Aramchol Administered under Fed Conditions in Healthy Chinese Volunteers (NCT 02803996)

The company performed the Chinese PK Study involving Chinese patients who are domiciled in the United States. The company enrolled 66 patients in this study, consisting of two parts. In part A, 32 subjects received a single escalating dose; Part B enrolled 34 subjects, which received a multiple escalating dose.

Phase 2b ARREST Study for Aramchol (NCT 02279524)

The FDA granted Fast Track designation status to Aramchol for the treatment of NASH. The company began its ARREST Study. The ARREST Study was a Phase 2b, multicenter, global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety and of two doses of Aramchol for the treatment of NASH in patients who are overweight or obese and have prediabetes or type II diabetes mellitus. In June 2018, the company announced top-line results of the ARREST Study and in November 2018 an oral abstract presentation of one-year results of the ARREST Study was presented during a Late Breaking Abstract Oral Session at The Liver Meeting 2018 during the American Association for the Study of Liver Diseases 2018 Annual Meeting.

Dose Splitting Pharmcokinetic Study (NCT03774173)

As a result of the dose response pattern observed in the ARREST Study, the company recently conducted a Phase 1, open-label, crossover PK study to assess whether dose splitting of Aramchol 600mg to twice daily 300mg will significantly increase plasma levels.

First in Human Aramchol Meglumine Pharmcokinetic Study

In December 2020, the company announced new data from a Phase 1, first in human study that compared Aramchol meglumine to Aramchol acid. Armachol acid and Aramchol megluine was administered twice daily to 12 subjects.

Phase 3 ARMOR Study for Aramchol

The Phase 3 study is a two-part study, an open-label part and a randomized, double-controlled, placebo part, designed to evaluate the safety and efficacy of Aramchol and to be conducted in approximately 200 sites in the U.S., Europe, and Latin America.

Aramchol for the Treatment of Other Indications

In July 2022, the company announced results showing significant effects of Aramchol in pre-clinical model of both lung and gastrointestinal (GI) fibrosis.

Strategic Collaborations, Research Arrangements and Other Agreements

Samil Pharma. Co., Ltd. (Samil)

The company has a license agreement, referred to herein as the Samil Agreement, with Samil for the commercialization of Aramchol (with the option to manufacture) in the Republic of Korea, or the Territory. Under the terms of the Samil Agreement, the company has granted Samil an exclusive licence, or the Samil License, for fatty liver indications, including NASH, or the Field of Use, in the Republic of Korea, or the Territory to such information concerning Aramchol as may be required to support Samil's applications for regulatory approvals, or the Licensed Information, and the patents for the import, marketing, use, sale, offer for sale, commercialisation and distribution (and, if the option is exercised, manufacture) of Aramchol in tablet form, or any other physical form as may be produced or manufactured by or on behalf of Galmed or by a third party for Galmed and, if the option set out below is exercised, any products within the Field of Use, the development, manufacture or sale of which is based, in whole or in part, on, or involves the use of, the Licensed Information or covered under any patent, or the Product.

Amilo 5-MER

The company has a research and option agreement with Yissum Research Development Company of the Hebrew University of Jerusalem (Yissum), the tech transfer company of the Hebrew University with respect to its Amilo-5MER, a 5 amino acid synthetic peptide MTADV (Methionine, Threonine, Alanine, Aspartic acid, Valine). Under this agreement, the company is able to research and initially develop Amilo-5MER, is required to fund the initial research and has been granted an exclusive option to negotiate and enter into a definitive license agreement with Yissum for Amilo-5MER upon certain pre-agreed upon terms and such other terms to be agreed upon.

Onkai

In January 2023, the company entered into a non-binding term sheet for an equity investment in Onkai, Inc. (Onkai), a U.S.-based technology company developing an AI-based platform to advance healthcare for underserved populations across the United States by facilitating alignment between healthcare stakeholders.

Intellectual Property

The company owns patent rights to Aramchol and Amilo-5MER in various jurisdictions worldwide, including within and outside of Israel. The company has sought patent protection in the United States and internationally for Aramchol and Amilo-5MER, its discovery programs, and any other inventions to which it has rights, where available and when appropriate. The term of U.S. Patent No. 7,501,403, covering the use of Aramchol for the treatment of fatty liver, has been extended by 567 days due to patent term adjustments, or PTA, resulting in an effective expiration date of November 3, 2023. The company has granted patents and pending patent applications in various jurisdictions relating to the composition of matter of Aramchol meglumine, as well as a wide range of other salts, or the CoM Patent; a method for treating/inhibiting hepatic fibrosis and non-hepatic fibrosis associated or non-associated with NASH or NAFLD, or the Hepatic Fibrosis Patent; and a method of treating dysbiosis, or the Dysbiosis Patent. In addition, the company has pending patent applications for Aramchol meglumine and other salts, including a granted U.S. patent for low dose composition of Aramchol (US 10,849,911 B2) and other salts. The company has been allowed or granted patents for Aramchol and other salts, which includes claims for the treatment of fatty liver in Europe and certain other countries. The CoM Patent application was granted on February 7, 2023 in the United States, allowed in Brazil on March 7, 2023 and is still pending in India. The CoM Patent that was granted in the United States expires on December 4, 2034, subject to appropriate maintenance, renewal, annuity or other governmental fees being paid. The Hepatic Fibrosis Patent has been granted in United States (US 11,197,870 B2) and Canada and in Israel and expires in each jurisdiction in 2037. The Dysbiosis Patent was granted in U.S., Israel, and Mexico and expires in each jurisdiction at the end of 2038 (including PTA). In addition, a patent applications were granted in Israel relating to Aramchol use in NAFLD and NASH treatments and in Mexico relating to Aramchol use to treat pulmonary fibrosis. Also, a patent was granted in Mexico and allowed, and will be granted on April 5, 2023, in Europe (EP 3538159) relating to Aramchol use for inhibition of fibrosis in NAFLD patients (having fibrosis score of zero (0)). The company also has pending patent applications (WO/2020/049556) for combination therapy for the treatment of liver disease in the United States, Canada, Europe, South Korea, India, Japan, China, Brazil, and Israel.

The company has an exclusive license to a U.S. granted patent directed to Amilo-5MER and anti-inflammatory compositions thereof. The U.S. Patent will be in full force and effect until July 15, 2035 subject to PTE of 84 day. On 24 January 2023 the company's collaborator, YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD was granted a new patent (US 11,560, 417 B2, a division of US 10,611,819 B2) for using the 5MER for the treatment of inflammatory diseases, which has 157 days of PTA and therefore should be valid until end of 2035.

The company also has a pending PCT international application, filed 2021, directed to peptides for treating acute respiratory distress syndrome. GALMED RESEARCH AND DEVELOPMENT LTD is a co-applicant in this PCT application with YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD. The patent term for this patent family is due to expire about on, 2041, not including any patent term extension.

Patent Portfolio for Aramchol and Aramchol Meglumine

The patent portfolio for Aramchol contains eight patent families, including pending patent applications and granted patents directed to composition of matter, manufacturing methods and methods of use.

The first patent family discloses and claims additional FABACs with different conjugation moieties, as well as the use of these and the compounds disclosed in the first patent family above, including Aramchol, in the treatment of fatty liver, reduction of serum cholesterol and treatment of hyperglycemia and diabetes. This patent family includes a U.S. patent directed to the treatment of fatty liver a U.S. patent directed to reduction of serum cholesterol by administering additional forms of FABACs, and a U.S. patent (Continuation-in-Part) directed to the treatment of hyperglycemia and diabetes. This patent family also includes two European patents, one patent, which was validated in Austria, Belgium, Cyprus, Denmark, Finland, France, Germany Ireland, Italy, Luxembourg, Monaco, the Netherlands, Portugal, Spain, Sweden, Switzerland, Turkey, and the United Kingdom, and the second patent, which was granted in Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Spain, Sweden, Switzerland, Turkey, and the United Kingdom. The family also includes patents in Australia, Canada, China, the Czech Republic, Azerbaijan, Belarus, Kyrgyzstan, Kazakhstan, the Russian Federation, Indonesia, Japan, Korea, Israel, Mexico, New Zealand, Norway, Poland, Hungary, and the Ukraine. A foreign patent application is granted in the Czech Republic. The non-extended patent term for this patent family expired on April 15, 2022, with the exception of the Israeli patent, which expired on April 17, 2021. The terms of the U.S. patents in this family have been extended due to patent term adjustments of 567 days for U.S. Patent 7,501,403, which is directed to the treatment of fatty liver, and 24 days for U.S. Patent 8,110,564, which is directed to reduction of serum cholesterol, and 356 days for U.S. Patent 8,975,246, which is directed to disorders associated with altered glucose metabolism or insulin action.

A second patent family directed to topical uses of FABAC compounds (anti-acne) was granted in Europe and maintained in Germany, France, Italy, the Netherlands, and the United Kingdom. If appropriate and the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term for this patent family is due to expire in August 2033, not including any patent term extension.

A third patent family discloses and claims second generation FABAC salt compounds include Aramchol meglumine. This patent family includes Granted U.S., shortly allowed in Brazil and still pending application in India and granted patents in Europe (maintained in Albania, Austria, Bulgaria, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, Greece, Hungary, Iceland, Italy, Latvia, Lithuania, Macedonia, Malta, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, the Netherlands, Turkey, Belgium, France, Germany, Ireland, Luxembourg, Malta, Monaco, Switzerland, and the United Kingdom), China, Hong Kong, Macau, Canada, Israel, Korea, and in Japan, as well as in Australia. If granted and the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term for this patent family is due to expire on December 4, 2034, not including any patent term extension.

A fourth patent family having one U.S. patent application, discloses and claims compositions comprising low doses of the second generation FABAC compounds Aramchol meglumine and other salts, which was granted by the U.S. Patent and Trademark Office (USPTO). When the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term for this patent family is due to expire in December 2034.

A fifth family is directed to treatment for modulating gut microbiota and/or dysbiosis using Aramchol. This patent family includes a granted patents in Israel, U.S. and in Mexico; and pending foreign patent applications in Brazil, Canada, China, Europe, Hong Kong, and Japan. When the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term for this patent family is due to expire in January 2036, not including any patent term extension. In the U.S. the granted patent has a patent term adjustment (681 days), hence it is due to expire about December 2038.

A sixth patent family and eighth family, both having PCT international applications filed in 2017 and two pending U.S. applications, are directed to uses of Aramchol and Aramchol meglumine for treating and inhibiting fibrosis. The two PCT applications entered National Phase in Australia, Brazil, Canada, China, Europe, Hong-Kong, Israel, Japan, Korea, and Mexico. It was granted in Canada and Israel and the treatment of pulmonary fibrosis was granted in Mexico. If granted and the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term of this patent family is due to expire in November 2037, not including any patent term extension. Additionally, a U.S. patent application directed to a method for treating hepatic fibrosis non-associated with non-alcoholic fatty acid liver disease - was granted, and is due to expire in October 2037. In addition, a U.S. continuation-in-part claiming priority to all of the above applications was filed in November 2018 and claims the treatment and inhibition of fibrosis by a regimen of 300 mg of Aramchol twice daily. The improved bio-availability of Aramchol is supported by the pharmacological model based on the preclinical and the ARREST data. Also, PCT application directed to treatment and inhibition of fibrosis by a regimen of 300 mg of Aramchol twice daily entered national phase in: Australia, Brazil, Canada, China, Europe, Israel, and Mexico. The Israeli national phase directed to the treatment and inhibition of fibrosis by a regimen of 300 mg of Aramchol twice daily - was granted. If granted and the appropriate maintenance, renewal, annuity or other governmental fees are paid, the non-extended term of this patent family is due to expire in October 2037, not including any patent term extension.

A seventh patent family is directed to a combination therapy of FABAC and at least one thyroid hormone receptor agonist or thyroid hormone mimetic for treating fatty liver disease; and has a PCT application, which entered National Phase in: Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, Korea, Mexico, and U.S. The patent term for this patent family is due to expire on September 3, 2038, not including any patent term extension.

Patent Portfolio for Amilo-5MER

The patent portfolio for Amilo-5MER contains three patent families, including pending patent applications and granted patents directed to composition of matter and methods of use.

The first patent family is directed to Amilo-5MER and anti-inflammatory compositions thereof. Galmed Research and Development Ltd. has an exclusive license to the U.S. granted patent within this family, and this U.S. patent will expire in October 2035, including 84 days of patent term adjustment. Galmed Research and Development Ltd. has also exclusive licenses to the corresponding granted patents in Europe, Australia, Japan, China, and India. The corresponding applications in Brazil, Korea, and Canada are pending. The non-U.S. patent term is due to expire in July 2035. A divisional application claiming the use of Amilo-5MER for the treatment of inflammatory diseases was granted in January 2023.

The second patent family is directed to peptides for treating acute respiratory distress syndrome. This family includes a pending PCT international patent application. Galmed Research and Development Ltd. is a co-applicant in this PCT application with Yissum. The patent term for this patent family is due to expire about in August 2041, not including any patent term extension.

Research and Development

For the year ended December 31, 2022, the company's research and development expenses were approximately $13.0 million.

Government Regulation and Product Approval

Aramchol or any other product candidate must be approved by the FDA through the New Drug Application (NDA) process before they may be legally marketed in the United States and by the Committee on Human Medicinal Products (CHMP), via the European Medicines Authority (EMA) and European Commission through the Marketing Authorization Application (MAA) process before they may be legally marketed in Europe, or the UK Medicines and Healthcare Products Regulatory Agency (MHRA) through its authorization procedures before they may be legally marketed in the U.K.

The relevant manufacturers of the company's drug substance and drug products for its current pre-clinical and clinical trials have advised it that they are compliant with both current good manufacturing practice (cGMP) and cGLP. The company and its contract manufacturers must ensure that all of the processes, methods and equipment are compliant with cGMP and cGLP for drugs on an ongoing basis, as mandated by the FDA and other regulatory authorities, and conducts extensive audits of vendors, contract laboratories and suppliers. The company's clinical CROs comply with guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, which attempt to harmonize the FDA, the European Medicines Authority (EMA), and the Pharmaceuticals and Medical Devices Agency of Japan regulations and guidelines.

History

Galmed Pharmaceuticals Ltd. was founded in 2000. The company was incorporated in Israel in 2013.