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News|Articles|July 16, 2025

Palatin’s Novel Oral Melanocortin-4 Receptor Demonstrates Rapid Weight Loss Potential in Preclinical Obesity Model

Preclinical study shows oral PL7737 agonist outperforms tirzepatide alone in rodent models, supporting Palatin’s plans for clinical trials targeting both general and rare forms of obesity.

Key Takeaways

  • PL7737 shows superior efficacy: High-dose PL7737 combined with tirzepatide resulted in 15% weight loss in preclinical models, outperforming tirzepatide alone.
  • MC4R agonists aid long-term weight maintenance: Low-dose bremelanotide sustained appetite suppression and prevented weight regain after GLP-1 therapy.
  • Topical melanocortin therapies show promise: PL9654 and PL9655 reduced inflammation and protected vision in diabetic retinopathy models, supporting expansion into ocular diseases.

Results from a preclinical study show that Palatin Technologies’ oral melanocortin-4 receptor (MC4R) agonist, PL7737, demonstrated significant weight loss in diet-induced obese (DIO) rodent models. According to the company, a high dose of PL7737 in combination with tirzepatide demonstrated significantly stronger results compared to tirzepatide alone.1

Can MC4R Agonists Such as PL7737 Outperform GLP-1 Drugs in Obesity Treatment?

"The rapid and significant weight loss seen with oral PL7737, both as monotherapy and in combination with tirzepatide in this established animal model, is impressive and suggests the potential for meaningful weight reduction in humans," said Carl Spana, PhD, president, CEO, Palatin, in a press release. "We are also evaluating PL7737 as a treatment for hypothalamic obesity and plan to begin a Phase I single- and multiple-ascending dose (SAD/MAD) clinical trial in late 2025, with data expected in the first half of 2026."

Preclinical Study Results Highlight Strong Synergy with Tirzepatide

  • Results after four days of treatment showed that the high dose of PL7737 demonstrated a 10% reduction and the combination achieved a 15% reduction, compared to 5% weight loss with tirzepatide alone.
  • Additionally, a middle dose of PL7737 demonstrated 5% weight loss and a middle dose in combination with tirzepatide demonstrated 11% weight loss.

Expanding the MC4R Obesity Pipeline

Palatin is also developing peptide-based MC4R agonists for weekly subcutaneous administration, with no observed hyperpigmentation, to expand therapeutic flexibility. In April, the company reported positive results from the Phase II BMT-801 trial, which combined the MC4R agonist bremelanotide with tirzepatide for appetite suppression.

The trial compared three treatment arms—bremelanotide alone, tirzepatide alone, and a combination of both—revealing comparable appetite suppression across all active treatment groups. Full results showed a 71% increase in appetite suppression with both bremelanotide alone and the combination therapy, compared to a 73% increase with tirzepatide alone. Bremelanotide also showed a 79% improvement in fullness and a 68% increase in satiety, which surpassed tirzepatide on these measures.1,2

Progress in Diabetic Retinopathy Research

In May, Palatin also revealed promising preclinical data from the novel melanocortin receptor agonists PL9654 and PL9655, which are in development for treating diabetic retinopathy. Results showed that both agonists resolved inflammation, stabilized the blood-retinal barrier, reduced vascular endothelial growth factor (VEGF) signaling, and protected retinal ganglion cells. Additionally, both agents maintained contrast vision, downregulated immune-related pathways in key retinal cells, and preserved cell integrity comparable to that of healthy controls.3

Obesity Prevalence and Strategic Opportunity

According to the Centers for Disease Control and Prevention, the prevalence of obesity in adults in the United States was 40.3% between August 2021 and August 2023. Overall, prevalence was higher in adults aged 40 to 59 years than in individuals aged 20 to 39 years of age or over 60 years of age. There were no significant differences between men and women.4

"Palatin is developing a strong pipeline of novel MC4R agonists to treat obesity,” continued Spana, in the press release. “Unlike incretin-based therapies, MC4R agonists offer a unique mechanism of action. In addition to oral PL7737, we have developed several selective peptide MC4R agonists designed for weekly subcutaneous administration, with no observed hyperpigmentation. Our deep expertise in melanocortin research allows us to efficiently advance both oral PL7737 and a long-acting peptide candidate, providing flexibility to target both general obesity and rare forms of the disease. We expect Phase 1 data for both programs in the first half of 2026."

References

  1. Palatin Announces Positive Preclinical Efficacy Data for Oral MC4R Agonist PL7737 in Animal Model of Obesity. PR Newswire. July 15, 2025. Accessed July 15, 2025. https://www.prnewswire.com/news-releases/palatin-announces-positive-preclinical-efficacy-data-for-oral-mc4r-agonist-pl7737-in-animal-model-of-obesity-302505219.html
  2. Palatin Reports Positive Appetite Suppression Results From Phase 2 Obesity Study of MC4R Agonist Bremelanotide and Tirzepatide. Palatin. April 17, 2025. Accessed July 15, 2025. https://palatin.com/press_releases/palatin-reports-positive-appetite-suppression-results-from-phase-2-obesity-study-of-mc4r-agonist-bremelanotide-and-tirzepatide/
  3. Palatin Presents Promising Preclinical Data on Melanocortin Agonists for Retinopathy at ARVO 2025. Palatin. May 9, 2025. Accessed July 15, 2025. https://palatin.com/press_releases/palatin-presents-promising-preclinical-data-on-melanocortin-agonists-for-retinopathy-at-arvo-2025/
  4. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. CDC. Accessed July 15, 2025. https://www.cdc.gov/nchs/products/databriefs/db508.htm

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