HT-VA / Rocket One - LARVOL DELTA

Hoth Therapeutics (HOTH) Reports Positive HT-VA CRADA Data: GDNF Reprograms Liver Fat Metabolism, Shuts Down Fat-Creation Gene and Activates Fat-Burning Pathways, Outperforming Semaglutide (PRNewswire) - "Statistically significant reduction in Srebf1, a key gene driving fat production in the liver; Increased expression of Pparα, a central regulator of fat metabolism and fat burning; GDNF outperformed semaglutide in key gene expression markers tied to liver fat regulation; Demonstrated broad metabolic impact at the genetic level, not just weight reduction...Srebf1 reduction → less fat being created; Pparα activation → more fat being burned; Net effect → reprogramming of liver metabolism...The HT-VA study evaluated the effects of parenteral GDNF in a diet-induced obesity and MAFLD model: Western diet significantly increased liver fat accumulation and metabolic dysfunction; GDNF treatment significantly improved liver gene expression linked to fat metabolism."

Preclinical • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Hoth Therapeutics Announces Groundbreaking Positive Results: Hoth's HT-VA GDNF Surpasses Semaglutide in Weight Loss, Glucose Control, and Liver Health in Obesity Model (PRNewswire) - "In female mice on a high-fat Western diet, GDNF attenuated weight gain by 10-15%, leading to a plateau in the final weeks of treatment—unlike semaglutide, which showed no significant impact...GDNF fully normalized fasting glucose and improved overall response to glucose challenges, outperforming semaglutide in females. Baseline improvements were also seen in males, indicating broad metabolic benefits...GDNF reduced liver weight by 20-30% and prevented adipose tissue accumulation in females, surpassing semaglutide's effects...Hoth plans to accelerate GDNF toward IND-enabling studies, targeting clinical trials in 2027."

New trial • Preclinical • Obesity

Hoth Therapeutics, Inc…announced the initiation of a U.S. Department of Veterans Affairs (VA)–backed study evaluating the potential of glial cell line–derived neurotrophic factor (GDNF)as a novel therapy for obesity and fatty liver disease (hepatic steatosis). (PRNewswire) - "The program is structured under Aim 1 of the approved Statement of Work (SOW), with key milestones as follows: October 2025 – Initiate high-fat and control diet groups; December 2025 – Begin GDNF and comparator dosing; January 2026 – Collect tissue samples and perform data analysis; Q1 2026– Initial results expected."

Clinical data • New trial • Obesity