Core Insights - Galmed Pharmaceuticals has signed a binding term-sheet with Entomus for a license agreement to develop and commercialize a proprietary Self-Emulsifying Drug Delivery System (SEDDS) for sublingual administration of peptides like GLP-1 [1] - The global GLP-1 market is projected to exceed $120 billion by 2030, with peak sales outside the US expected to reach approximately $20 billion by 2032 [3] - The new sublingual formulation aims to enhance bioavailability, reduce side effects, and improve patient compliance compared to existing injectable and oral forms of semaglutide [6][9] Company Developments - The definitive agreement with Entomus will outline milestone payments and future royalty payments, expected to be finalized within 90 days [1] - The sublingual semaglutide formulation is anticipated to be approved through the expedited 505(b)(2) regulatory pathway [5][6] - Galmed aims to initially target markets with high rates of type 2 diabetes and obesity, such as India, Brazil, and the GCC region, where patent protections for semaglutide are less stringent [4][5] Industry Context - The first-pass effect in oral medications can reduce efficacy, while sublingual administration offers a non-invasive alternative that allows direct entry into the bloodstream [2] - The increasing prevalence of type 2 diabetes and obesity in various global markets creates a favorable environment for GLP-1 therapies [4] - Semaglutide, as a GLP-1 receptor agonist, has shown significant efficacy in managing blood glucose levels and promoting weight loss, positioning it as a transformative treatment option [7]

Core Viewpoint - Galmed Pharmaceuticals has initiated a research collaboration with Virginia Commonwealth University to explore the potential of Aramchol in overcoming drug resistance in gastrointestinal cancers, particularly colorectal and hepatocellular cancers, aiming to enhance treatment efficacy against these aggressive tumors [1][5]. Group 1: Collaboration Details - The collaboration involves VCU scientists studying Aramchol in preclinical models, focusing on its ability to prevent or reverse resistance to standard therapies such as targeted kinase inhibitors and chemotherapies [1][2]. - The project is based on recent research highlighting the role of lipid metabolic pathways, specifically Stearoyl-CoA Desaturase 1 (SCD1), in driving drug resistance in GI tumors [2][5]. - Galmed will provide funding and Aramchol materials, while VCU will conduct the studies, leveraging its expertise in cancer biology and drug resistance [7]. Group 2: Market Implications - This partnership marks a strategic expansion for Galmed beyond its historical focus on fibrotic liver diseases into oncology, targeting a significant market with high unmet needs [4][5]. - Aramchol is the most clinically advanced SCD1 inhibitor, with a strong safety profile demonstrated in previous trials, presenting a unique opportunity in cancer treatment [4][5]. - The collaboration aims to generate proof-of-concept data that could lead to further clinical development in oncology, potentially expanding Galmed's pipeline and enhancing its commercial prospects [6][7]. Group 3: Clinical Context - A significant proportion of patients with advanced hepatocellular carcinoma (HCC) do not benefit from current second-line therapies due to drug resistance, with most developing resistance within six months [3][6]. - Targeting lipid metabolism with Aramchol is seen as a promising strategy to overcome resistance to tyrosine kinase inhibitors (TKIs), which are pivotal in treating advanced HCC [6][3]. - The collaboration aims to develop safe drug combinations that can block and circumvent drug resistance in HCC, addressing a critical need in cancer treatment [3][6].

Core Insights - Galmed Pharmaceuticals has unveiled novel pharmacodynamic blood markers for its lead compound, Aramchol, which is the most clinically advanced SCD1 inhibitor in the industry, indicating potential applications beyond NASH therapy [1][3] - The collaboration with Proteas Health has led to the identification of a panel of 70 plasma proteins that can track Aramchol's therapeutic impact, providing a single blood-based pharmacodynamic signature for monitoring patient response [2][5] - The findings suggest that Aramchol may reduce chronic systemic inflammation, oxidative stress, and atherosclerotic plaque pathogenesis, highlighting its broad therapeutic relevance in cardiometabolic diseases [3][8] Company Developments - Galmed is focusing on expanding its clinical pipeline to include additional cardiometabolic and potentially oncological indications, leveraging the insights gained from the pharmacodynamic markers [3][9] - The company aims to develop a cost-effective, high-throughput assay to measure Aramchol's unique pharmacodynamic signature, which could enhance clinical trials and drug response evaluation [5][6] - CEO Allen Baharaff emphasized that the newly discovered markers could serve as early indicators of Aramchol's efficacy, opening avenues for future research in cardiovascular diseases [4][6] Industry Context - The collaboration with Proteas Health is positioned to reduce clinical trial risks and accelerate commercialization pathways for Aramchol, addressing the global burden of cardiometabolic and fibro-inflammatory conditions [6][10] - The ability to demonstrate and monitor Aramchol's impact through a single blood test is expected to transform clinical development and create new commercialization opportunities [6][10]

Core Insights - Galmed Pharmaceuticals has announced positive preliminary results from the AM-001 Study, marking a significant step in the development of Aramchol Meglumine, an improved formulation of its lead compound [1][7] - Aramchol Meglumine is a New Chemical Entity (NCE) with patent protection until 2035, being developed for various indications related to fatty acid metabolism [1][2] - The initial findings indicate that Aramchol Meglumine has higher bioavailability compared to Aramchol free acid, with a once-daily 200 mg dose likely to be optimal for future trials [1][5] Company Development - Galmed has successfully advanced Aramchol acid through six clinical trials, enrolling 661 subjects, establishing its safety and efficacy in treating NASH (MASH) [2] - The transition from Aramchol acid to Aramchol Meglumine was approved by the FDA, requiring only a bioavailability study for comparison [3][4] - The AM-001 study aims to identify optimal doses for advancing Aramchol Meglumine into Phase 2 studies, with Part 2 expected to conclude in the second half of 2025 [4] Clinical Findings - Preliminary results from Part 1 of the AM-001 study show that a 400 mg dose of Aramchol Meglumine achieved an area under the curve (AUC) nearly double that of Aramchol acid tablets [5] - The findings suggest that a once-daily regimen simplifies patient adherence and is expected to lower manufacturing costs [5][7] Strategic Outlook - Galmed's commitment to accelerating the clinical program for Aramchol Meglumine is reinforced by the positive data from the AM-001 study [7] - The company aims to leverage the enhanced bioavailability and robust patent protection of Aramchol Meglumine to drive growth and deliver innovative therapies for unmet medical needs [7][8] - Galmed is also pursuing opportunities to expand its product pipeline, targeting cardiometabolic diseases and gastrointestinal cancers [8]

Company Overview - Galmed Pharmaceuticals Ltd. is a clinical-stage biopharmaceutical company focused on liver, cardiometabolic diseases, and GI oncological indications [1][3] - The company is developing Aramchol for oncological indications outside of liver disease and is actively pursuing opportunities to expand its product pipeline [3] Financial Reporting - Galmed has filed its Annual Report on Form 20-F for the fiscal year ended December 31, 2024, with the U.S. Securities and Exchange Commission [1] - The report is accessible on the SEC's website and Galmed's Investor Relations website [2] Strategic Focus - The company aims to diversify its product pipeline specifically targeting cardiometabolic indications and other innovative product candidates [3]

Financial Performance - The company reported a loss attributable to holders of ordinary shares of approximately $6.9 million for the year ended December 31, 2023, and $7.5 million for 2024, with an accumulated deficit of $200.5 million as of December 31, 2024[40]. - The company has a history of operating losses and expects to continue incurring significant expenses and operating losses for the foreseeable future[41]. - The company anticipates needing substantial additional capital in the future to fund operations and develop Aramchol, with future capital requirements dependent on various factors including clinical trial costs and regulatory pathways[51]. - The company may incur substantial costs in pursuing future capital financing, including investment banking and legal fees, which could adversely impact financial condition[55]. - The company has no committed external sources of funds and may face significant capital outlays and operating expenditures for anticipated clinical trials, risking delays or terminations if adequate funds are not available[53]. Cash and Capital Resources - As of December 31, 2024, the company had cash and cash equivalents of $4.7 million, restricted cash of $0.1 million, short-term deposits of $3.5 million, and marketable debt securities of $7.2 million, indicating a net working capital of $14.0 million[50]. - As of March 21, 2025, the public float was approximately $5.0 million, limiting the company to raise funds up to $1.67 million under the Baby Shelf Rule until the public float exceeds $75 million[52]. - Any additional capital raised through equity sales will dilute current shareholders' ownership and could decrease the market price of ordinary shares[57]. Product Development and Regulatory Challenges - The company has not yet commercialized any products and may never be able to do so, with significant uncertainty surrounding the regulatory approval process for its lead product candidate, Aramchol[47]. - The clinical trial process is complex and expensive, with potential delays due to regulatory requirements, recruitment challenges, and funding limitations[70]. - The regulatory approval process for NASH drugs remains uncertain, with significant challenges including high screen failure rates and the reliance on subjective liver biopsies as a primary endpoint[80]. - The FDA has indicated that a single Phase 3 study must demonstrate a high level of efficacy to support an NDA, which adds to the uncertainty of approval even if statistical goals are met[81]. - The company has completed seven clinical trials of Aramchol, but future trials could reveal undesirable side effects that may affect regulatory approval and market acceptance[93]. Market and Competitive Landscape - The market for Aramchol faces intense competition from larger pharmaceutical companies with significantly greater resources and experience in drug development and commercialization[150]. - Competitors in the NASH field include Novo Nordisk, Akero Therapeutics, Madrigal Pharmaceuticals, and Viking Therapeutics, with Madrigal Pharmaceuticals recently announcing FDA approval for Rezdiffra for NASH treatment[152]. - The company anticipates facing increasing competition as new drugs and advanced technologies enter the market, which could render Aramchol non-competitive or obsolete[151][153]. Intellectual Property Risks - The company faces risks related to intellectual property, including the potential failure to obtain or maintain sufficient patent protection for its technologies and product candidates[185]. - The company may rely on third-party patents, which could require payment of significant fees or royalties, impacting the ability to develop and commercialize products[197]. - If third-party patents are found to be valid and enforceable, the company may be blocked from commercializing its product candidates unless licenses are obtained, which may not be feasible[201]. Compliance and Regulatory Environment - Compliance with healthcare and data privacy laws is critical, as violations could result in penalties and harm the company's reputation[130]. - The company must navigate various federal and state laws, including the Anti-Kickback Statute and the False Claims Act, which impose significant compliance requirements[131]. - The evolving regulatory environment surrounding AI may require significant adjustments to data practices and policies, incurring substantial costs[137]. Operational and Strategic Challenges - The company has no sales or distribution capabilities and intends to rely on third parties for the commercialization of Aramchol, which may limit revenue generation[178]. - The company currently does not intend to develop a marketing and sales force, which may limit its ability to market product candidates directly and could result in lower revenues[179]. - Future collaboration arrangements with pharmaceutical or biotechnology companies may not be successful, impacting the development and commercialization of product candidates[180]. Environmental and Economic Factors - The company may incur substantial costs related to compliance with environmental, health, and safety regulations, which could adversely affect financial performance[113]. - Economic conditions, including inflation and geopolitical events, may adversely affect the company's operating results and financial condition[219].

Core Viewpoint - Galmed Pharmaceuticals has secured a new patent for the combination therapy of Aramchol and Resmetirom for treating non-alcoholic steatohepatitis (NASH), extending patent protection until September 2039, which positions the company to capitalize on the commercial potential of Aramchol in the growing NASH market [1][2][5]. Company Summary - Galmed Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing Aramchol for liver and fibro-inflammatory diseases, particularly NASH [12]. - The company believes that Aramchol's unique mechanism of action as a stearoyl-CoA desaturase-1 (SCD1) modulator provides a competitive advantage, making it suitable for combination therapies [6][7]. - The recent patent strengthens Galmed's intellectual property portfolio, enhancing its strategic flexibility for partnerships and commercialization [11]. Industry Summary - The global NASH treatment market is projected to grow from approximately $5.2 billion in 2022 to over $48 billion by 2035, indicating significant unmet needs and revenue opportunities [5]. - The industry is shifting towards combination therapies for NASH, as no single agent is expected to fully address the disease's complexities [4][10]. - Recent regulatory developments, including the FDA's approval of Resmetirom as the first drug for NASH patients with liver fibrosis, highlight the therapeutic potential in this area [4].

Core Insights - Galmed Pharmaceuticals has reported significant anti-fibrotic effects of Aramchol 300mg BID in patients with metabolic dysfunction associated steatohepatitis (MASH) [1][2] - The results from the Open-Label part of the Phase 3 trial (ARCON) have been published in the journal Hepatology, confirming the drug's efficacy through multiple objective measurements [1][5] - Aramchol is recognized as the most advanced down regulator of SCD-1 in clinical development, influencing fatty acid oxidation and reducing glycemic parameters [3] Company Overview - Galmed Pharmaceuticals is focused on developing Aramchol for liver diseases and exploring its potential for other fibro-inflammatory and oncological indications [6] - The company believes that combination therapy will be the optimal treatment for MASH, positioning Aramchol as a potent anti-fibrotic compound in the competitive landscape [4] Clinical Study Insights - The Phase 3 trial involved 150 patients with NASH and fibrosis, demonstrating a high rate of histological fibrosis improvement with Aramchol treatment [2] - The study utilized advanced digital pathology techniques, including AI analysis, to assess histological changes, enhancing the sensitivity and dynamic range of fibrosis scoring [1][5] Expert Commentary - Prof. Vlad Ratziu, a lead author of the study, emphasized the innovative mode of action of Aramchol and its potential for treating fibrotic MASH, highlighting the rigorous assessment methods used in the study [5]

Core Insights - Galmed Pharmaceuticals (NASDAQ: GLMD) has seen its stock price surge nearly 400%, with trading volume exceeding 80 million shares compared to an average of 75,000 shares [1][3][5] Company Overview - Galmed Pharmaceuticals is a small-cap biopharmaceutical company based in Tel Aviv, Israel, focusing on therapeutics for liver diseases, particularly non-alcoholic steatohepatitis (NASH) [3][4] - The company's leading product, Aramchol, is an oral therapy currently in Phase III trials for treating NASH in patients with obesity and type II diabetes [3] - Galmed is also exploring Aramchol for other conditions, including liver disease related to HIV, and is developing a synthetic peptide, Amilo-5MER, with partnerships with Samil Pharma and OnKai [4] Reasons for Stock Surge - The stock's surge is attributed to two main factors: 1. **Regaining Nasdaq Compliance**: Galmed's SEC filing on September 16, 2024, indicated that the company regained compliance with Nasdaq's minimum bid price requirement, which had previously put it at risk of delisting [6] 2. **Short Squeeze Driven by Technical Factors**: The primary driver of the stock's rise is its unique trading dynamics, characterized by a small float of approximately 600,000 shares. The Relative Volume (RVOL) reached over 600, indicating trading at 600 times the average daily volume, leading to a significant short squeeze [7][8] Investment Considerations - The stock's volatility and low liquidity make it more suitable for short-term traders rather than long-term investors, as it is prone to dramatic price swings [9][10] - While the stock has potential for high returns, it also carries significant risks, making it appealing for day traders but dangerous for those seeking stable, long-term investments [10]

As filed with the Securities and Exchange Commission on August 30, 2024. Washington, DC 20549 Registration No. 333- FORM F-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 GALMED PHARMACEUTICALS LTD. (Exact name of registrant as specified in its charter) UNITED STATES SECURITIES AND EXCHANGE COMMISSION State of Israel 2834 Not Applicable (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identification Number) c/o ...