Hoth Therapeutics Inc. (NASDAQ:HOTH) recently announced detailed preclinical data from an investigative study evaluating the efficacy of glial cell-derived neurotrophic factor (GDNF) as a treatment for obesity and metabolic-associated steatotic liver disease (MASLD). This research initiative, financially supported by the U.S. Veterans Administration (VA), builds upon previous evidence suggesting a protective effect of GDNF against diet-induced obesity.
The preclinical experiments entailed a comparative analysis between GDNF and semaglutide, the latter being the active pharmaceutical component in Novo Nordisk A/S' (NYSE:NVO) widely prescribed agents Wegovy and Ozempic. The findings showcased that GDNF provided superior outcomes across several crucial measures, including the stabilization of body weight, improvement of glucose tolerance, reduction in liver mass, and regulation of adipose tissue accumulation. Notably, these beneficial impacts were particularly pronounced in female test subjects.
During an exclusive discussion on Tuesday, Hoth Therapeutics emphasized that the experimental data position GDNF as a potential disruptive force within the $200 billion obesity treatment sector. The compound offers a mechanistic differentiation that could circumvent some limitations associated with current GLP-1 receptor agonists such as gastrointestinal side effects and muscle degradation.
With over one billion individuals affected worldwide by obesity and MASLD impacting up to 30% of adults, the multi-pronged metabolic advantages demonstrated by GDNF could signify a major breakthrough in therapeutic strategies for these conditions.
Preclinical Study Outcomes
- In female mice subjected to a high-fat Western diet, administration of GDNF resulted in a 10-15% attenuation of weight gain. Unlike semaglutide, which failed to show statistically significant effects on weight in the same cohort, GDNF treatment led to a weight plateau during the latter weeks of the trial period.
- Researchers highlighted that the efficacy of GDNF might be further enhanced with increased dosage or extended treatment duration, implying potential for sustained and amplified weight reduction in future studies.
- When assessing glucose metabolism, GDNF fully restored fasting glucose levels to normal and improved responses to glucose tolerance tests in female subjects. Baseline metabolic improvements were also recorded in male subjects, indicating broader applicability.
- Hepatic analyses revealed that GDNF decreased liver weight by 20-30% and inhibited accumulation of adipose tissue in female models, outperforming semaglutide's efficacy in these parameters.
Next Steps in Development
Further investigations will include comprehensive assessments of liver pathology, quantification of lipid content, and examination of gene and protein expression to elucidate GDNF's underlying mechanisms of action. Hoth Therapeutics has outlined plans to expedite the GDNF program towards Investigational New Drug (IND)-enabling studies, with aspirations to initiate clinical trials in 2027.
GDNF sits within a broader Hoth Therapeutics pipeline that includes HT-001, currently in Phase 2 trials targeting cancer-related skin toxicities; HT-KIT, which holds Orphan Drug Designation for mast cell cancers; and HT-ALZ, aimed at Alzheimer’s disease treatment.
Recent Progress on Other Fronts
In January, Hoth Therapeutics reported intermediate results from the open-label pharmacokinetic cohort of CLEER-001, an ongoing trial assessing HT-001 in oncology patients undergoing EGFR inhibitor therapy. Notably, all evaluable participants in this cohort achieved a clinical response by six weeks, alongside a near 50% reduction in disease severity as assessed by investigators using the ARIGA scale.
Market Response
Following the announcement, shares of Hoth Therapeutics closed with a modest increase, trading at $0.87 during premarket sessions on Tuesday, as captured by Benzinga Pro data.
Conclusion
This emerging evidence positions GDNF as a candidate for a novel obesity and MASLD treatment that may overcome efficacy and tolerability challenges faced by prevailing standards of care. While these preclinical results are compelling, confirmation through rigorous clinical trials remains essential to establish safety and therapeutic value in humans.