Positive preclinical data on melanocortin agonists for retinopathy

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Palatin Technologies recently announced preclinical data on the company’s melanocortin agonists PL9654 and PL9655.

Both agents were found to have efficacy across multiple models and routes of administration, including topical delivery, and the findings demonstrating both PL9654 and PL9655’s ability to resolve inflammation, stabilize the blood-retinal barrier, reduce VEGF signaling, and protect retinal ganglion cells – all play a role in diabetic retinopathy-associated vision loss.

Key findings:¹

• Vision preservation: Both PL9654 and PL9655 maintained contrast vision and showed significant efficacy compared to vehicle.
• Inflammation control: Gene set enrichment analysis showed the downregulation of immune-related pathways in microglia and Müller glial cells for both PL9654 and PL9655 compared to vehicle.
• Retinal protection: PL9654 reduced ischemia-reperfusion-induced retinal damage, similar to the melanocortin peptide α-MSH.
• Cell integrity: Microglia and Müller glial cell levels in treated animals mirrored those in healthy controls.
• Neuroregeneration: Topical PL9655 treatment increased rod photoreceptor levels relative to vehicle.
• Anti-angiogenesis: PL9654 significantly inhibited choroidal neovascularization and fibrosis. PL9655 topical treatment also showed an increase in rods compared to vehicle.

“Palatin’s melanocortin research data are unparalleled in demonstrating multi-pathway inflammation resolution,” said Carl Spana, PhD, President and CEO of Palatin. “The ability to modulate immune response, suppress angiogenesis, and preserve neural integrity, especially via topical administration, could transform treatment for retinal diseases like diabetic retinopathy.”

Diabetic retinopathy (DR) is a progressive, diabetes-related complication that causes damage to the blood vessels in the retina, which leads to vision loss and blindness. Affecting up to 80% of people with diabetes for 20 years or more, DR is one of the leading causes of vision impairment among adults aged 20 to 64 years old.

Paul Kayne, PhD, Vice President, Biological Sciences at Palatin presented the data in a poster titled, “Activating the melanocortin system resolves inflammation, reduces VEGF signaling in diabetic retinopathy (DR), and provides retinal ganglion cell (RGC) protection,” during the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting held May 4-8 in Salt Lake City.

Reference

1. Palatin Technologies, Inc. Palatin Presents Promising Preclinical Data on Melanocortin Agonists for Retinopathy at ARVO 2025. Prnewswire.com. Published May 9, 2025. Accessed May 13, 2025. https://www.prnewswire.com/news-releases/palatin-presents-promising-preclinical-data-on-melanocortin-agonists-for-retinopathy-at-arvo-2025-302450810.html