Hoth Therapeutics Signs VA Research Deal to Advance GDNF as Breakthrough Therapy for Obesity and Fatty Liver - Side-by-Side Study vs. Semaglutide Begins

Rhea-AI Summary

Hoth Therapeutics (NASDAQ: HOTH) has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. Department of Veterans Affairs and FAVER to study GDNF as a potential treatment for obesity and fatty liver disease.

The research will be conducted at the Atlanta VA Medical Center through a dual-arm study comparing GDNF against semaglutide. The first arm will evaluate GDNF in Western diet-fed mice, while the second arm will test GDNF in human hepatocyte-engrafted mice. Under the agreement, Hoth will fund the study and provide GDNF, with the VA maintaining data rights.

GDNF has previously shown promise in reducing body weight, enhancing insulin sensitivity, and promoting fatty acid oxidation. This study represents the first pharmacologic test of GDNF in human liver-engrafted mice, potentially expanding its applications beyond CNS indications.

Positive

• First-ever pharmacologic test of GDNF in human liver-engrafted mice
• Direct comparison study against market leader semaglutide
• Previous positive safety data from human trials in Parkinson's disease
• Potential expansion into large obesity and fatty liver disease markets

Negative

• Early-stage research with no guaranteed success
• Daily injection requirement could limit commercial potential
• Study costs will be funded by Hoth, impacting cash reserves

Insights

Biotechnology Research Analyst

Hoth's GDNF research agreement with VA potentially positions them in the lucrative weight loss market against established drugs like semaglutide.

Hoth Therapeutics has secured a strategic research partnership through a Cooperative Research and Development Agreement (CRADA) with the VA and Foundation for Atlanta Veterans Education and Research that could significantly advance their metabolic disease pipeline. The agreement focuses on evaluating GDNF (glial cell-derived neurotrophic factor) as a potential therapeutic for obesity and fatty liver disease - two massive market opportunities.

What makes this particularly noteworthy is the head-to-head comparison with semaglutide, the active ingredient in blockbuster weight loss drugs Wegovy and Ozempic. This comparative study design suggests Hoth is positioning GDNF as a potential competitor in the rapidly expanding GLP-1 dominated weight loss market, estimated to reach $100 billion by 2030.

The dual-arm approach is methodologically sound, utilizing both standard diet-induced obese mice and human liver chimeric mouse models - the latter being particularly valuable as it incorporates human hepatocytes to better predict clinical outcomes. This translational approach significantly derisks the path to human trials by providing human-relevant data at the preclinical stage.

GDNF's mechanism appears complementary but distinct from GLP-1 agonists like semaglutide. While both may result in weight loss, GDNF's ability to enhance insulin sensitivity and promote fatty acid oxidation suggests potential metabolic benefits beyond simple appetite suppression. The fact that GDNF has previously demonstrated safety in human trials for Parkinson's disease also provides a regulatory advantage, potentially allowing for an accelerated development timeline.

However, investors should note this remains early-stage research with no guarantee of clinical success. The deal structure, where Hoth funds the study while the VA retains data rights, is standard for CRADAs but limits Hoth's exclusive control over research outputs. The news represents a meaningful scientific step forward but commercial applications remain years away if successful.

NEW YORK, July 22, 2025 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharma innovator, today announced a CRADA (Cooperative Research and Development Agreement) with the U.S. Department of Veterans Affairs and Foundation for Atlanta Veterans Education and Research (FAVER) to evaluate GDNF (glial cell-derived neurotrophic factor) as a novel metabolic therapy targeting obesity and hepatic steatosis (fatty liver disease).

The study, conducted at the Atlanta VA Medical Center, will benchmark daily GDNF injections against semaglutide in both standard diet-induced obese mice and human liver chimeric mouse models, a gold-standard translational platform.

Dual-Arm Study: Head-to-Head vs. Semaglutide

CRADA Title:

"Efficacy of Parenteral GDNF Administration in the Induction of Weight Loss and Resolution of Hepatic Steatosis"

Study Highlights:

• Arm 1: Western diet-fed CF-1 mice treated with GDNF vs. placebo and semaglutide — tracking weight loss, liver histology, and metabolic markers.
• Arm 2: GDNF administered to TK-NOG human hepatocyte-engrafted mice — assessing human liver-specific gene expression, pathology, and glucose metabolism.

All protocols are IRB-approved and comply with VA and federal research ethics standards.

Deal Structure & Value

Under the agreement:

• Hoth Therapeutics will fund the study
• Hoth will supply GDNF while the VA retains data rights and shares de-identified results per HIPAA-compliant CRADA terms.

Key Collaborators:

• Hoth Therapeutics, Inc.
• U.S. Department of Veterans Affairs
• Foundation for Atlanta Veterans Education and Research (FAVER)

Why It Matters: Scientific Rationale

GDNF has demonstrated the ability to:

• Reduce body weight and hepatic lipid accumulation in prior transgenic models
• Enhance insulin sensitivity and promote fatty acid oxidation
• Show clinical safety in previous human trials (Parkinson's disease)

This CRADA marks the first pharmacologic test of GDNF in human liver-engrafted mice — setting the stage for potential first-in-class metabolic applications beyond CNS indications.

"This landmark agreement allows a real-world, controlled comparison of GDNF's metabolic effects alongside semaglutide — the current gold standard," said Robb Knie, CEO of Hoth Therapeutics. "We are proud to support the VA's efforts in exploring bold new solutions for obesity and liver disease."

Learn more: www.hoththerapeutics.com

About Hoth Therapeutics, Inc.
Hoth Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative, impactful, and ground-breaking treatments with a goal to improve patient quality of life. We are a catalyst in early-stage pharmaceutical research and development, elevating drugs from the bench to pre-clinical and clinical testing. Utilizing a patient-centric approach, we collaborate and partner with a team of scientists, clinicians, and key opinion leaders to seek out and investigate therapeutics that hold immense potential to create breakthroughs and diversify treatment options. To learn more, please visit https://ir.hoththerapeutics.com/.

Forward-Looking Statement
This press release includes forward-looking statements based upon Hoth's current expectations, which may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, and are subject to substantial risks, uncertainties, and assumptions. These statements concern Hoth's business strategies; the timing of regulatory submissions; the ability to obtain and maintain regulatory approval of existing product candidates and any other product candidates we may develop, and the labeling under any approval we may obtain; the timing and costs of clinical trials, and the timing and costs of other expenses; market acceptance of our products; the ultimate impact of the current coronavirus pandemic, or any other health epidemic, on our business, our clinical trials, our research programs, healthcare systems, or the global economy as a whole; our intellectual property; our reliance on third-party organizations; our competitive position; our industry environment; our anticipated financial and operating results, including anticipated sources of revenues; our assumptions regarding the size of the available market, benefits of our products, product pricing, and timing of product launches; management's expectation with respect to future acquisitions; statements regarding our goals, intentions, plans, and expectations, including the introduction of new products and markets; and our cash needs and financing plans. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. You should not place reliance on these forward-looking statements, which include words such as "could," "believe," "anticipate," "intend," "estimate," "expect," "may," "continue," "predict," "potential," "project" or similar terms, variations of such terms, or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section titled "Risk Factors" in Hoth's most recent Annual Report on Form 10-K and Hoth's other filings made with the U. S. Securities and Exchange Commission. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates, and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance, or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events, or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.

Investor Contact:
LR Advisors LLC 
Email: investorrelations@hoththerapeutics.com
www.hoththerapeutics.com
Phone: (678) 570-6791

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SOURCE Hoth Therapeutics, Inc.

FAQ

What is the purpose of Hoth Therapeutics' GDNF study with the VA?

The study aims to evaluate GDNF as a potential treatment for obesity and fatty liver disease, comparing it directly against semaglutide in both standard diet-induced obese mice and human liver chimeric mouse models.

How will HOTH's GDNF be compared to semaglutide in the study?

The study includes two arms: one comparing GDNF against semaglutide in Western diet-fed mice, and another testing GDNF in human hepatocyte-engrafted mice to assess liver-specific effects.

What previous results has GDNF shown in metabolic conditions?

GDNF has demonstrated ability to reduce body weight, enhance insulin sensitivity, promote fatty acid oxidation, and has shown safety in human trials for Parkinson's disease.

Who are the key partners in Hoth Therapeutics' GDNF research agreement?

The key partners are Hoth Therapeutics, the U.S. Department of Veterans Affairs, and the Foundation for Atlanta Veterans Education and Research (FAVER).

What is the financial structure of HOTH's GDNF research agreement?

Under the agreement, Hoth Therapeutics will fund the study and supply GDNF, while the VA retains data rights and shares de-identified results following HIPAA-compliant CRADA terms.