Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) announced on April 28, 2025, that it has signed a binding term sheet with Entomus s.r.o. to develop and commercialize a novel sublingual formulation of semaglutide, the active ingredient in blockbuster GLP-1 medications Ozempic and Wegovy.
The agreement centers on a proprietary Self-Emulsifying Drug Delivery System (SEDDS) formulation that enables sublingual administration of peptide drugs like semaglutide through orally dispersible films. This technology allows the medication to enter the bloodstream directly through the oral mucous membranes, bypassing the digestive system.
Novel Delivery System Addresses Key Treatment Barriers
The sublingual delivery system aims to overcome significant limitations of current semaglutide formulations. Injectable versions (Ozempic and Wegovy) can cause patient discomfort and anxiety, while the oral version (Rybelsus) faces reduced bioavailability due to first-pass metabolism in the liver.
"The proposed transmucosal administration route could potentially enhance the bioavailability in comparison with Rybelsus and reduce the daily dose of semaglutide," said Allen Baharaff, President and CEO of Galmed Pharmaceuticals. "We also expect less side effects and more rigid pharmacokinetic profile with more precise control of blood sugar level."
The companies expect to execute a definitive agreement within 90 days, which will determine milestone payments and future royalty structures.
Strategic Market Positioning
Galmed's strategy appears focused on markets where semaglutide patents will expire earliest. While patent protection in the US, EU, and Japan extends to 2028-2031, other significant markets have no such restrictions, with patents beginning to expire as early as 2026.
These markets include India, Brazil, Gulf Cooperation Council countries, Singapore, Hong Kong, South Africa, Turkey, and Mexico – regions with rapidly growing rates of type 2 diabetes mellitus (T2DM) and obesity.
The global GLP-1 market is experiencing explosive growth, with Jefferies projecting it to reach over $120 billion in obesity and T2DM treatments by 2030. Ex-US peak sales are forecast at approximately $20 billion by 2032.
Regulatory and Development Pathway
Galmed believes the development program could potentially be approved through an expedited 505(b)2 regulatory pathway, which allows some reliance on previously established safety and efficacy data for the active ingredient.
This approach could significantly reduce development time and costs compared to traditional approval routes, allowing Galmed to bring the product to market more rapidly in targeted regions.
Expanding Therapeutic Applications
Semaglutide, a GLP-1 receptor agonist that mimics natural hormones involved in glucose regulation, has demonstrated remarkable efficacy beyond diabetes treatment. Its ability to promote significant weight loss has positioned it as a breakthrough therapy for obesity management.
The drug is also being investigated for various metabolic, cardiovascular, and oncological indications, expanding its potential therapeutic applications.
Strategic Diversification for Galmed
This agreement represents a strategic expansion for Galmed, which has historically focused on developing Aramchol for liver diseases. The company has recently been seeking to advance Aramchol for oncological indications outside of non-alcoholic steatohepatitis (NASH) and fibrosis.
"We believe this will allow Galmed to embark on a rapid development program in the highly lucrative GLP-1 space," Baharaff noted. "This delivery method's appeal is offering an alternative to injectable routes which can be a barrier for some patients."
Market Impact and Future Outlook
The development of a sublingual semaglutide formulation could significantly disrupt the rapidly growing GLP-1 market by addressing key limitations of current delivery methods. If successful, the technology could improve patient compliance while maintaining or enhancing therapeutic efficacy.
For patients reluctant to use injectable medications but requiring more reliable absorption than oral tablets provide, a sublingual film could represent an ideal middle ground, potentially expanding the overall market for GLP-1 therapies.
As obesity and diabetes rates continue to rise globally, particularly in emerging markets, innovative delivery systems for effective treatments like semaglutide will likely play a crucial role in addressing these growing public health challenges.
