Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) announced top-line results from its joint research with Virginia Commonwealth University (VCU) demonstrating that a three-drug combination of Aramchol, Stivarga® (regorafenib), and metformin significantly enhanced gastrointestinal tumor cell killing in both laboratory and animal models. The study builds on breakthrough findings published in Nature Communications linking Aramchol to overcoming cancer drug resistance.
Synergistic Anti-Cancer Effects Demonstrated
The latest preclinical study revealed the mechanism of action behind Aramchol's anti-tumor abilities when used alone or in combination with the multi-kinase inhibitor regorafenib and the type 2 diabetes drug metformin. According to the company, the three-drug combination showed synergistic effects with potential for development as a fixed-dose combination treatment.
Previously in May 2025, Galmed reported that Aramchol significantly enhanced regorafenib's effectiveness in gastrointestinal cancer models. In that study, Aramchol enhanced both flux and autolysosome formation caused by regorafenib, activating ATM and AMPK pathways while inactivating mTORC1 and mTORC2 pathways. The combination suppressed tumor growth in hepatoma models without causing normal tissue toxicities.
Addressing Drug Resistance in GI Cancers
Allen Baharaff, President and CEO of Galmed Pharmaceuticals, highlighted the clinical need addressed by this combination approach. "Stivarga® (regorafenib) is indicated as standard-of-care third line treatment in metastatic colorectal cancer (CRC), as well as advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma," Baharaff stated.
He noted that monoclonal antibodies such as atezolizumab and bevacizumab serve as first-line therapy for these patients, but approximately 75% of patients develop resistance or intolerance to these treatments. The high cost of monoclonal antibodies also limits their cost-effectiveness, creating an opportunity for alternative treatment strategies.
Commercial and Patent Strategy Implications
Stivarga represents Bayer's top-selling cancer drug, generating €458 million (~$500 million) in the first nine months of 2022, representing a 28% increase from 2021. However, the main patent protection for regorafenib is expected to expire in August 2028 in Europe and July 2032 in the U.S., potentially opening the market to generic competition.
"Based on the top-line results, a fixed dose combination with Aramchol has shown that such combination could potentially become a life-cycle IP strategy for regorafenib to help delay the generic competition," Baharaff explained. The company has submitted new patent applications (US 63/786,370 and US 63/915,832) to the USPTO for this combination approach.
Clinical Development Timeline
The combination of Aramchol and Stivarga is expected to enter Phase 1b clinical trials in early 2026 in patients with metastatic colorectal cancer, hepatocellular carcinoma, and cholangiocarcinoma, with a planned expansion cohort including metformin. The Phase 1b study will be conducted at VCU Massey Comprehensive Cancer Center and will serve as proof-of-concept for Aramchol's efficacy in an oncology clinical setting.
"Positive findings could lay the groundwork for subsequent accelerated clinical development of Aramchol in key three GI cancers, which if successful, could potentially expand Galmed's pipeline and create value for investors and stakeholders," Baharaff noted.
Company Background and Strategic Focus
Galmed Pharmaceuticals is a clinical-stage biopharmaceutical company that has historically focused on developing Aramchol for liver disease treatment. The company is now seeking to advance Aramchol's development for oncological indications beyond NASH and fibrosis. As part of its growth strategy, Galmed is actively pursuing opportunities to expand and diversify its product pipeline, specifically targeting cardiometabolic indications and other innovative product candidates that align with its core drug development expertise.
