Aramchol (aramchol meglumine) / Galmed, Weizmann Institute of Science - LARVOL DELTA

The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo. (PubMed, Oncotarget) - "Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect. Knock down of Beclin1 reduced the lethality of regorafenib and aramchol as single agents and when combined whereas knock down of LAMP2 or BID did not reduce killing caused by aramchol as a single agent but did reduce the lethality of regorafenib alone and regorafenib plus aramchol. In vivo using the HuH7 adult hepatoma cell line, regorafenib and aramchol interacted to suppress tumor growth without normal tissue toxicities."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • AMPK • ATG16L1 • BECN1 • HSPA5 • LAMP2 • SCD

Aramchol attenuates fibrosis in mouse models of biliary fibrosis and blocks the TGFβ-induced fibroinflammatory mediators in cholangiocytes. (PubMed, Hepatol Commun) - "Aramchol attenuates and prevents biliary fibrosis in mouse models of cholestatic liver disease by inhibiting TGFβ-induced fibroinflammatory mediators and activating PPARa/γ in cholangiocytes. These findings, combined with its favorable clinical safety profile, support the potential of Aramchol as a therapeutic candidate for PSC."

Journal • Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • ABCB4 • IL6 • PDGFB • PPARA • SCD • TGFB1 • TNFA

A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Galmed Pharmaceuticals Ltd | N=24 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal

Galmed Identifies Proprietary Biomarker Signature for Aramchol, Unlocking Multi-Billion-Dollar Expansion Potential Beyond NASH (PRNewswire) - P3 | N=157 | ARMOR (NCT04104321) | Sponsor: Galmed Research and Development, Ltd. | "Galmed Pharmaceuticals Ltd... announced a major scientific and strategic milestone: the discovery of a proprietary pharmacodynamic (PD) blood-based biomarker signature for its lead candidate, Aramchol — the industry's most clinically advanced stearoyl-CoA desaturase 1 (SCD1) inhibitor....70-Protein PD Signature: Identified through advanced proteomics and AI in collaboration with Proteas Health, a leader in precision biomarker development. This signature was observed at Week 12 post-treatment in the ARMOR trial. Reduction in Systemic Inflammation & Cardiac Stress: Biomarker shifts reflect decreases in key drivers of chronic inflammation, oxidative stress, and atherosclerotic plaque formation."

Biomarker • P3 data • Metabolic Dysfunction-Associated Steatohepatitis

Galmed Reports Significant Anti-Fibrotic Effects of Aramchol in PSC Models (Galmed Pharma Press Release) - "Galmed Pharmaceuticals Ltd...announced today results showing significant effects of Aramchol in pre-clinical models of primary sclerosing cholangitis (PSC)....Aramchol, an SCD-1 inhibitor, both attenuated and prevented biliary fibrosis in mouse models of PSC. Aramchol significantly reduced, in a dose-dependent manner, the increased expression of the fibrotic marker plasminogen activator inhibitor-1 and hepatic stellate cell-activating genes (VEGFA and PDGFB) in TGFβ-activated transformed human cholangiocyte cells (H69) and mouse large biliary epithelial cells (MLEs). Aramchol led to a significant inhibition of TGFβ-induced hepatic fibrosis pathways while upregulating peroxisome proliferator activated receptor (PPAR) signaling."

Preclinical • Primary Biliary Cholangitis

Galmed Announces First Time Results in Oncology Studies: Aramchol Significantly Enhances Bayer’s Regorafenib Effect in GI Cancer Models (PRNewswire) - "Results from studies at Virginia Commonwealth University (VCU) show that an Aramchol and Bayer's Regorafenib drug combination significantly reduced hepatic tumor growth in mice models. The cell killing effect in-vitro and in-vivo was due to increased autophagy and death receptor signaling. A Phase 1b Study of the addition of Aramchol to Regorafenib in patients with advanced GI cancers is planned to be initiated at VCU's Massey Cancer Center in Q4 2025."

P1 data • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer

Galmed Pharma Shares Jump 10% On Cancer Drug Data: Retail Traders Turn ‘Extremely Bullish’ (MSN News) - "Galmed Pharmaceuticals (GLMD) shares rose sharply on Tuesday after the company reported positive preclinical data showing that its experimental drug Aramchol enhances the effectiveness of Regorafenib in liver and colon cancer models. Following the announcement, Galmed's stock rose by 10.6%, closing at $1.46 per share."

Commercial • Colon Cancer • Colorectal Cancer

Galmed Announces First Time Results in Oncology Studies: Aramchol Significantly Enhances Bayer's Regorafenib Effect in GI Cancer Models (PRNewswire) - "Results from studies at Virginia Commonwealth University (VCU) show that an Aramchol and Bayer's Regorafenib drug combination significantly reduced hepatic tumor growth in mice models; The cell killing effect in-vitro and in-vivo was due to increased autophagy and death receptor signaling; A Phase 1b Study of the addition of Aramchol to Regorafenib in patients with advanced GI cancers is planned to be initiated at VCU's Massey Cancer Center in Q4 2025."

New P1 trial • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer

Galmed Pharmaceuticals Launches VCU Collaboration to Tackle Drug Resistance in GI Cancers (Galmed Pharma Press Release) - "Galmed Pharmaceuticals Ltd...announced a sponsored research collaboration with Virginia Commonwealth University (VCU) to investigate Aramchol's potential in overcoming drug resistance in gastrointestinal (GI) cancers. Under the Sponsored Project Agreement, VCU scientists will study Aramchol in preclinical models of advanced GI malignancies – focusing on colorectal and hepatocellular (liver) cancers – in combination with standard-of-care treatments. The goal is to determine whether Aramchol's novel mechanism of action can prevent or reverse resistance to therapies such as targeted kinase inhibitors and chemotherapies, thereby enhancing their efficacy against these aggressive tumors....This collaboration addresses a critical unmet need: GI cancers (including colon and liver cancers) are among the leading causes of cancer mortality worldwide, and treatment options are often limited by therapy resistance."

Commercial • Preclinical • Colon Cancer • Gastrointestinal Cancer • Liver Cancer

Galmed Unveils Novel Pharmacodynamic Blood Markers for Aramchol, the Most Clinically Advanced SCD1 Inhibitor (PRNewswire) - "Galmed Pharmaceuticals Ltd...announces the unveiling of novel pharmacodynamic (PD) blood markers for its lead compound, Aramchol, the industry's most clinically advanced SCD1 inhibitor. These newly identified biomarkers shed fresh light on Aramchol's potential far beyond its role in NASH (MASH) therapy—offering a deeper understanding of the drug candidate's biochemical impact and presenting an exciting opportunity to enhance clinical decision-making and expand into additional disease areas....Galmed's analysis revealed that this signature aligns with reduced chronic systemic inflammation, oxidative stress, and atherosclerotic plaque pathogenesis—key drivers in cardiometabolic diseases. Significantly, the data also demonstrate a marked reduction in ANP (Atrial Natriuretic Peptide), widely recognized as an established clinical biomarker for heart failure and left ventricular dysfunction. Moreover, the findings indicate a stimulated..."

Clinical • Cardiovascular • Fibrosis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Galmed Announces Positive Part 1 Results from the AM-001 Study of Aramchol Meglumine, an Enhanced Formulation of the Most Clinically Advanced SCD1 Inhibitor (Galmed Pharma Press Release) - P1 | N=16 | NCT06502561 | Sponsor: Galmed Pharmaceuticals Ltd | "The AM-001 study was conducted in response to that FDA request and is also designed to help identify the doses best suited for advancing Aramchol Meglumine into Phase 2 studies. It consists of two parts, comparing single doses of Aramchol acid and Aramchol Meglumine in healthy volunteers. Part 2 of the study is anticipated to conclude in the second half of 2025....In Part 1 of AM-001, preliminary results demonstrate that a 400 mg dose of Aramchol Meglumine suspension achieved an area under the curve (AUC) nearly double that of Aramchol acid tablets. Based on these outcomes, 200 mg once daily appears to be the optimal dose for subsequent clinical trials. This once-daily regimen not only simplifies patient adherence (moving from twice-daily to once-daily) but is also expected to reduce the overall cost of goods."

P1 data • Trial status • Immunology

Galmed Pharmaceuticals Secures New Patent Grant Extending Aramchol's Patent Protection to 2039, Strengthening Leadership in NASH/MASH Combination Therapy (PRNewswire) - "Galmed Pharmaceuticals...today announced the grant of a new patent related to its lead compound, Aramchol. The patent covers the use of a combination therapy of Aramchol and Resmetirom (MGL-3196, Rezdiffra) for the treatment of non-alcoholic steatohepatitis (NASH), also known as metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis. With this latest patent, Galmed is strengthening and extending Aramchol's patent protection through September 2039, securing long-term market exclusivity for its novel NASH therapy....Commercial interest in NASH is surging – according to a recent report published by the international consulting firm Research Nester, the global NASH treatment market is projected to grow from about $5.2 billion in 2022 to over $48 billion by 2035, reflecting enormous unmet need and revenue opportunity."

Commercial • Patent • Fibrosis • Metabolic Dysfunction-Associated Steatohepatitis

Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Galmed Pharmaceuticals Ltd | Not yet recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2025 ➔ May 2025

Enrollment closed • Trial primary completion date

Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Galmed Pharmaceuticals Ltd | Initiation date: Oct 2024 ➔ Jan 2025

Trial initiation date

A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR) (clinicaltrials.gov) - P3 | N=157 | Suspended | Sponsor: Galmed Research and Development, Ltd. | N=2000 ➔ 157

Enrollment change • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Aramchol attenuates fibrosis in mouse models of biliary fibrosis and blocks the TGFβ-induced fibroinflammatory mediators in cholangiocytes. (PubMed, bioRxiv) - "This effect is partially due to Aramchol inhibiting TGFβ-induced fibroinflammatory mediators in cholangiocytes by upregulating PPARα and -γ expression and activity. These findings, along with Aramchol's excellent safety profile in clinical trials, provide the rationale for assessing Aramchol in further clinical studies in patients with biliary fibrosis, particularly PSC, where a treatment is desperately needed."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • ABCB4 • IL6 • PDGFB • PPARA • SCD • SERPINE1 • TGFB1 • TNFA

ARAMCHOL, A STEAROYL-COA DESATURASE INHIBITOR, ATTENUATES THE TGFΒ-STIMULATED FIBROINFLAMMATORY SIGNALS IN CHOLANGIOCYTE MODELS OF PRIMARY SCLEROSING CHOLANGITIS (AASLD 2024) - "Aramchol, an SCD inhibitor, attenuates the TGFβ-stimulated activation of the fibroinflammatory response in cholangiocytes partly through activating PPARγ. These findings warrant further investigation in PSC including in vivo models."

Fibrosis • Hepatology • Immunology • Inflammation • IL6 • PPARG • SCD • SERPINE1 • TGFB1

POTENTIAL USE OF IPSC-DERIVED HEPATOCYTE-LIKE CELLS TO DEVELOP PRECISION MEDICINE FOR ASH (AASLD 2024) - "Treatment with Aramchol, a fatty acid pathway modulator, led to decreased LD formation and senescence... iPSCs generated from whole blood can be induced to differentiate into iHLCs, which can be further characterized by transcriptome analyses. In vitro exposure of iHLCs to ethanol induced lipid accumulation and upregulated fatty acid synthesis pathways. iHLCs were also generated from ASH patients' blood samples and their further characterization may facilitate the development of precision therapeutics."

Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • CD4

A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis (clinicaltrials.gov) - P2 | N=24 | Suspended | Sponsor: Galmed Pharmaceuticals Ltd | Trial completion date: Dec 2026 ➔ Dec 2027 | Not yet recruiting ➔ Suspended | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Trial suspension • Hepatology

Galmed Announces an Expansion of its Activities to Cancer and major Cardiometabolic Diseases (PRNewswire) - "Galmed Pharmaceuticals Ltd...announced today that based on the recently published results from the Open-Label part of its Phase 3 NASH study, new scientific publications on the role of SCD1 as a critical metabolic signaling hub as well as an extended cash runway, it plans to broaden its drug development activities...The planned expansion consists of two additional programs over the next two years. One program aims to identify novel Aramchol-based drug combinations to overcome resistance to standard-of-care oncological treatments for patients with advanced colorectal and hepatic cancers. Another program aims to unravel new mechanisms of action that will allow the development of a novel Aramchol-based drug combination targeting cardiac fibrosis, or scarring of the heart...The Company plans on releasing new data from in-vitro and ex-vivo studies in these programs during the fourth quarter of 2024."

Pipeline update • Preclinical • Cardiovascular • Colorectal Cancer • Fibrosis • Gastrointestinal Cancer • Liver Cancer • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, J Clin Transl Hepatol) - "Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs...Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications."

Journal • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Type 2 Diabetes Mellitus • FGF21 • TNFA

Open-Label Study to Evaluate the Safety, Tolerability, and PK of Aramchol in Subjects With Hepatic Impairment (clinicaltrials.gov) - P1 | N=57 | Completed | Sponsor: Galmed Research and Development, Ltd. | Enrolling by invitation ➔ Completed

Trial completion • Hepatology

Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Galmed Pharmaceuticals Ltd

New P1 trial

A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Galmed Research and Development, Ltd. | Initiation date: Jun 2024 ➔ Jun 2025

Trial initiation date • Hepatology

Aramchol improves hepatic fibrosis in MASH: Results of multimodality assessment using both conventional and digital pathology. (PubMed, Hepatology) - "Continuous fibrosis scores generated in antifibrotic trials by DIA quantify antifibrotic effects with greater sensitivity and larger dynamic range than CP."

Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • SCD