Hoth Therapeutics' GDNF Study Outperforms Semaglutide in Key Metrics
Written by Emily J. Thompson, Senior Investment Analyst
Updated: 1h ago
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Should l Buy HOTH?
Source: stocktwits
- Significant Research Findings: Hoth Therapeutics' study revealed that GDNF led to a 10% to 15% reduction in weight gain in female mice on a high-fat diet over 12 weeks, while semaglutide showed no meaningful effects, indicating GDNF's potential in weight management.
- Liver Health Improvement: The GDNF treatment resulted in a 20% to 30% reduction in liver weight and effectively prevented fat accumulation, highlighting its applicability in addressing obesity-related fatty liver disease, which could introduce new treatment options to the market.
- Positive Market Reaction: Although HOTH shares rose over 5% in pre-market trading, they fell 6% after the opening bell, reflecting initial investor optimism regarding the GDNF study results and the potential for new therapies in the obesity treatment landscape.
- Future Research Plans: Hoth intends to conduct further studies to better understand GDNF's mechanisms, with clinical trials targeted for 2027, aiming to drive innovation in the obesity treatment sector and enhance the company's competitiveness in the rapidly growing weight-loss drug market.
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Analyst Views on HOTH
About HOTH
Hoth Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing new generation therapies for unmet medical needs. The Company is focused on developing a topical formulation for treating side effects from drugs used for the treatment of cancer (HT-001); a treatment for mast-cell derived cancers and anaphylaxis (HT-KIT), and a treatment and/or prevention for Alzheimer's or other neuroinflammatory diseases (HT-ALZ). The Company also has assets being developed for atopic dermatitis (also known as eczema) (BioLexa); a treatment for asthma and allergies using inhalational administration (HT-004), and a treatment for obesity, and obesity-related diseases and conditions (HT-VA).
About the author

Emily J. Thompson
Emily J. Thompson, a Chartered Financial Analyst (CFA) with 12 years in investment research, graduated with honors from the Wharton School. Specializing in industrial and technology stocks, she provides in-depth analysis for Intellectia’s earnings and market brief reports.
- Significant Weight Loss: In female mice on a high-fat Western diet, GDNF reduced weight gain by 10-15%, unlike semaglutide, indicating GDNF's substantial potential in obesity treatment and offering a new therapeutic option.
- Enhanced Glucose Metabolism: GDNF fully normalized fasting glucose levels and outperformed semaglutide in glucose challenge responses, demonstrating broad metabolic benefits, particularly in female models.
- Liver and Adipose Tissue Health: GDNF reduced liver weight by 20-30% and prevented adipose tissue accumulation in females, surpassing semaglutide's effects, highlighting its promise in addressing obesity-related fatty liver disease.
- Study Design and Future Plans: Conducted at the Srinivasan Lab over 12 weeks, Hoth plans to accelerate GDNF towards IND-enabling studies, targeting clinical trials in 2027, further advancing its application in the $200 billion obesity market.
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- Significant Research Findings: Hoth Therapeutics' study revealed that GDNF led to a 10% to 15% reduction in weight gain in female mice on a high-fat diet over 12 weeks, while semaglutide showed no meaningful effects, indicating GDNF's potential in weight management.
- Liver Health Improvement: The GDNF treatment resulted in a 20% to 30% reduction in liver weight and effectively prevented fat accumulation, highlighting its applicability in addressing obesity-related fatty liver disease, which could introduce new treatment options to the market.
- Positive Market Reaction: Although HOTH shares rose over 5% in pre-market trading, they fell 6% after the opening bell, reflecting initial investor optimism regarding the GDNF study results and the potential for new therapies in the obesity treatment landscape.
- Future Research Plans: Hoth intends to conduct further studies to better understand GDNF's mechanisms, with clinical trials targeted for 2027, aiming to drive innovation in the obesity treatment sector and enhance the company's competitiveness in the rapidly growing weight-loss drug market.
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- Preclinical Study Results: Hoth Therapeutics' GDNF, co-developed with the U.S. Veterans Administration, demonstrated superior efficacy compared to semaglutide across key metrics such as weight stabilization, glucose tolerance, liver weight reduction, and adipose tissue control, particularly in female models, indicating its potential disruptive impact in the $200 billion obesity market.
- Multiple Treatment Advantages: GDNF's multifaceted benefits could address the gastrointestinal side effects and muscle loss associated with current GLP-1 agonists, offering new solutions for over 1 billion obese individuals globally and up to 30% of adults affected by MASLD, highlighting its strategic significance in the healthcare landscape.
- Future Research Directions: Hoth plans to accelerate GDNF toward IND-enabling studies, targeting clinical trials in 2027, with future analyses including liver pathology, lipid content, and gene/protein expression to further elucidate mechanisms, showcasing the company's ongoing commitment to R&D.
- Corporate Strategic Vision: CEO Robb Knie emphasized that the results of GDNF research represent a monumental step forward in the fight against obesity, creating significant value for shareholders and demonstrating the company's dedication to developing safer, more effective therapies that enhance patient quality of life.
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- Significant Study Results: Hoth Therapeutics' research indicates that GDNF shows remarkable efficacy in obesity and metabolic-associated steatotic liver disease, particularly in female models where weight loss reached 10-15%, contrasting with semaglutide's lack of significant impact, suggesting GDNF could be a game-changing treatment in the obesity market.
- Mechanistic Advantages: GDNF outperformed semaglutide in key metrics, including weight stabilization, improved glucose tolerance, and reduced liver weight, highlighting its potential to address limitations of current GLP-1 agonists, particularly gastrointestinal side effects and muscle loss.
- Future Research Directions: Hoth plans to accelerate GDNF toward IND-enabling studies, targeting clinical trials in 2027, with future analyses including liver pathology, lipid content, and gene/protein expression to further elucidate mechanisms.
- Broad Market Potential: With over 1 billion people affected by obesity globally and MASLD impacting up to 30% of adults, GDNF's multifaceted benefits could revolutionize treatment paradigms, making Hoth's GDNF program strategically significant within its pipeline.
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- Clinical Response Rate: In the open-label PK cohort of the CLEER-001 trial, 100% of evaluable patients achieved a clinical response by Week 6, demonstrating the efficacy of HT-001 in cancer patients and potentially laying the groundwork for future treatment options.
- Disease Severity Improvement: There was approximately a 50% reduction in disease severity (ARIGA score) from baseline, with all evaluable patients reaching ARIGA ≤1 by Week 6, indicating significant and durable treatment effects that enhance the company's competitive position in oncology.
- Reduction in Side Effects: Supportive clinical endpoints showed a ~34% improvement in oncology toxicity (CTCAE) and a ~37% reduction in patient-reported pruritus, highlighting a broad and consistent treatment effect across multiple clinically relevant measures, which may improve patient quality of life.
- Market Performance Analysis: Hoth Therapeutics' stock is currently trading at $1.075, 2.7% below its 20-day simple moving average, indicating a bearish trend in the short term, although analysts maintain a 'Buy' rating with a price target of $6.50, reflecting confidence in the company's future potential.
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- Primary Endpoint Improvement: In the CLEER-001 trial's open-label PK cohort, HT-001 reduced ARIGA scores from a baseline of 1.67 to 0.83, representing a ~50% improvement in disease severity, with all evaluable patients achieving low-severity status by Week 6, demonstrating rapid onset and durability of response.
- Oncology Toxicity Reduction: HT-001 showed significant improvements in additional endpoints, with a ~34% reduction in oncology toxicity (CTCAE) and a ~37% decrease in patient-reported pruritus, indicating a broad and consistent treatment effect across multiple clinically relevant measures.
- Favorable Tolerability: HT-001 was well tolerated in the open-label PK cohort, with no unexpected safety signals observed, supporting the efficacy of the selected dosing regimen and continued clinical development.
- Potential Supportive Care: The results highlight HT-001's potential as an important oncology supportive-care therapy, aiding patients in maintaining effective cancer treatments and improving their quality of life amidst the challenges posed by EGFR inhibitors.
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