Palatin Technologies, Inc. announced Frontiers in Immunology published a manuscript, "Pro-resolving and anti-arthritic Properties of the MC1 Selective Agonist PL8177, summarizing data demonstrating PL8177 provides therapeutic effects in inflammatory conditions, including arthritis. Palatin, in collaboration with The William Harvey Research Institute, Queen Mary University of London, in London, UK, conducted the study to assess the immunopharmacology of a PL8177 in vitro and in a mouse model of inflammatory arthritis. Key findings included PL8177 activation of mouse and human MC1 receptors and that PL8177 displayed pro-resolving activity (enhanced macrophage efferocytosis) and counteracted the inflammatory profile of zymosan-stimulated macrophages, reducing the release of IL-1ß, IL-6, TNF-a and CCL-2. In the context of joint inflammation, PL8177 reduced the clinical score, paw swelling and incidence of severe disease as well as the recruitment of immune cells into the arthritic joint.

The authors on the paper were Jose Garrido-Mesa and Bethan Lynne Thomas of The William Harvey Research Institute, John Dodd and Carl Spana of Palatin, and Mauro Perretti and Trinidad Montero-Melendez of The William Harvey Research Institute and the Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London. Drugs targeting the melanocortin system have emerged as promising therapeutics for several conditions, including inflammatory diseases, obesity and sexual dysfunction, with several already FDA approved. As illustrated in the publication, melanocortins are peptides that have anti-inflammatory and pro-resolving effects.

Many of these effects are mediated by the melanocortin receptor 1 as reported in several experimental settings. As such, MC1r can be a viable target for the development of new therapies that mimic endogenous pro-resolving mediators. Palatin has multiple MC1r agonist candidates in pre-clinical and clinical development.

Palatin is conducting a Phase 2 multi-center, randomized, double-blind, placebo-controlled, adaptive design, clinical study of PL8177, with once daily (QD) oral dosing in adult UC subjects. The study is designed to enroll up to 28 adult subjects with active UC from approximately 22 sites. All subjects who meet the eligibility criteria will be randomized to receive either placebo or oral PL8177.

The PL8177-205 interim assessment is expected to occur in the first quarter of calendar year 2023, with final topline data anticipated in the second quarter of calendar year 2023. PL8177 is a synthetic cyclic heptapeptide with demonstrated efficacy in multiple animal inflammatory bowel disease models. PL8177 is a potent, selective agonist at the human melanocortin receptor-1, with sub-nanomolar affinity binding and EC50 functional values.

Palatin data demonstrates that the oral formulation of PL8177 was protected from degradation in the stomach and small intestine and delivered to the large intestine and colon over an extended period. In addition, orally administered PL8177 had a significant effect on resolving inflammation in a rat bowel inflammation model. PL8177 in oral formulations has demonstrated repeated, robust efficacy in ulcerative colitis disease models.

MC1r is found on epithelial cells and resident macrophages of the colon which are accessible from the lumen of the colon. Orally administered PL8177 is not systemically absorbed. PL8177 has the potential for excellent efficacy without safety concerns.Ulcerative colitis is a chronic disease of the large intestine (colon), with inflammation and ulcerations that can cause significant abdominal pain, persistent diarrhea, loss of appetite and other symptoms. An estimated 1 million individuals in the United States are affected by ulcerative colitis, with over 350,000 diagnosed with moderate-to-severe disease.

Existing treatments are not effective in a substantial portion of patients with moderate-to-severe ulcerative colitis, with certain severe cases resulting in surgical removal of the colon.