Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) has announced breakthrough results from oncology studies showing that its drug Aramchol significantly enhances the anti-tumor effects of Bayer's Regorafenib in gastrointestinal (GI) cancer models. This marks Galmed's first foray into oncology applications for Aramchol, previously studied primarily for liver diseases.
The studies, conducted at Virginia Commonwealth University (VCU), demonstrated that the combination of Aramchol and Regorafenib significantly reduced hepatic tumor growth in mice models without causing normal tissue toxicities. The enhanced cell-killing effect was attributed to increased autophagy and death receptor signaling.
Mechanism of Action and Synergistic Effects
Aramchol, a first-in-class Stearoyl-CoA Desaturase 1 (SCD1) inhibitor, was found to interact with multiple tyrosine kinase inhibitors (TKIs) including Sorafenib, Regorafenib, and Lenvatinib to kill GI tumor cells, with Regorafenib exhibiting the strongest synergistic effect.
The research revealed that Aramchol enhanced both flux and autolysosome formation caused by Regorafenib, activating ATM and AMPK while inactivating mTORC1 and mTORC2 pathways. This synergistic mechanism provides a scientific foundation for further clinical development.
"The key molecular mechanisms by which Aramchol and Regorafenib killed GI tumor cells were defined in the study," explained Paul Dent, Ph.D., Professor at VCU's School of Medicine. "Aramchol acts to enhance autophagy through mechanisms that are different to those of Regorafenib. The interaction between Aramchol and Regorafenib, causing more autophagic flux and autolysosome formation, is required for the enhanced killing of tumor cells by the drug combination."
Addressing Drug Resistance in GI Cancers
This development builds on Galmed's recently announced collaboration with VCU to investigate Aramchol's potential in overcoming drug resistance in GI cancers. The collaboration, formalized through a Sponsored Project Agreement in April 2025, aims to address a critical unmet need in cancer treatment.
GI cancers, including colorectal and hepatocellular carcinomas, are among the leading causes of cancer mortality worldwide. Treatment options are often limited by therapy resistance, particularly to TKIs such as Regorafenib.
Recent research published in Nature Communications has highlighted the role of lipid metabolic pathways, notably SCD1, in driving drug resistance in GI tumors. By targeting SCD1, Aramchol offers a novel therapeutic strategy that could potentially reprogram tumor metabolism and sensitize cancer cells to existing treatments.
Clinical Development Plans
Based on these promising preclinical results, Galmed plans to initiate a Phase 1b clinical trial evaluating the addition of Aramchol to Regorafenib in patients with advanced GI cancers. The study is expected to begin at VCU's Massey Cancer Center in Q4 2025.
"Targeting lipid metabolism with Aramchol, a potent SCD1 inhibitor, is a promising emerging strategy to overcome TKIs therapy resistance in HCC and colorectal cancers," said Allen Baharaff, President and CEO of Galmed Pharmaceuticals. "A combination of Bayer's Regorafenib and Aramchol could potentially become a cost-effective first line treatment for HCC and other liver and colorectal cancers."
Strategic Expansion Beyond Liver Disease
For Galmed, this initiative represents a strategic expansion beyond its historical focus on fibrotic liver diseases into the oncology arena. The company plans to advance this novel combination oncology program in parallel to its recently announced Semaglutide GLP-1 development.
Aramchol's dual action on metabolic and fibrotic pathways, combined with its strong safety profile demonstrated in previous clinical trials, presents a unique opportunity in cancer treatment. The drug's extended patent protection through 2035 further enhances the commercial prospects of any new oncological application.
Market Implications
Hepatocellular carcinoma (HCC) remains the only major cancer for which death rates have not improved over the last decade. While monoclonal antibodies have emerged as first-line therapy for patients with HCC, approximately 75% of patients are refractory to or intolerant of these treatments, and their high cost limits cost-effectiveness.
The Aramchol-Regorafenib combination could potentially offer a more affordable alternative with improved efficacy. By leveraging Aramchol's ability to inhibit SCD1 and potentially reverse drug resistance, Galmed aims to address a significant unmet need in the treatment of GI cancers.
The collaboration between Galmed and VCU combines the pharmaceutical company's decade-long experience with Aramchol in metabolic diseases with VCU's expertise in cancer biology and drug resistance models. Both parties believe this partnership can accelerate the path toward a first-in-class therapy that tackles cancer resistance mechanisms head-on.
