Hoth Therapeutics Inc. (HOTH) thinks it might have something special on its hands. The company released preclinical data Tuesday showing its experimental obesity drug based on glial cell-derived neurotrophic factor (GDNF) beat Novo Nordisk's (NVO) semaglutide—the active ingredient in Wegovy and Ozempic—across several key measures.
The study, backed by the U.S. Veterans Administration, builds on earlier research suggesting GDNF protects against diet-induced obesity. This time, researchers ran a direct comparison against semaglutide to see how the two compounds stack up. The results favored GDNF, particularly in female test models, across weight stabilization, glucose tolerance, liver health, and fat tissue control.
Hoth told MarketDash the findings position GDNF as a potential disruptor in the massive obesity treatment space, which has ballooned into a $200 billion market. The drug's different mechanism of action could address some limitations of current GLP-1 agonists, including gastrointestinal side effects and muscle loss that patients sometimes experience.
The Numbers That Matter
In female mice fed a high-fat Western diet, GDNF reduced weight gain by 10-15%, eventually causing weight to plateau in the final weeks of treatment. Semaglutide showed no significant impact on weight in the same conditions. Researchers noted that higher doses or longer treatment periods might amplify GDNF's effects even further.
The glucose control results were equally striking. GDNF completely normalized fasting glucose levels and improved overall glucose challenge responses, outperforming semaglutide in females. Male test subjects also showed baseline improvements, suggesting the metabolic benefits extend across both sexes.
For liver health, GDNF reduced liver weight by 20-30% and prevented fat tissue accumulation in females, again surpassing semaglutide's effects. Given that metabolic-associated steatotic liver disease (MASLD) affects up to 30% of adults and obesity impacts over 1 billion people worldwide, a drug that tackles both conditions simultaneously could reshape treatment approaches.
What Comes Next
Hoth plans additional analyses examining liver pathology, lipid content, and gene and protein expression to better understand how GDNF works. The company is accelerating the program toward IND-enabling studies with an eye toward clinical trials starting in 2027.
GDNF is just one piece of Hoth's pipeline. The company is also developing HT-001, currently in Phase 2 trials for cancer-related skin toxicities, HT-KIT for mast cell cancers (which has Orphan Drug Designation), and HT-ALZ for Alzheimer's disease.
Earlier this year, Hoth shared interim results from its CLEER-001 trial evaluating HT-001 in cancer patients receiving EGFR inhibitor therapy. In that study's open-label pharmacokinetic cohort, 100% of evaluable patients achieved clinical response by Week 6, with disease severity dropping by roughly 50% from baseline on the ARIGA scale.
Hoth Therapeutics (HOTH) shares rose 1.83% to $0.87 in premarket trading Tuesday.
