Palatin Technologies announced positive results of a micro-dose study of radiolabeled PL-8177 using an oral, delayed-release, polymer formulation. The study met all primary and secondary endpoints. PL-8177 is a patented melanocortin receptor 1 agonist with potential application in treatment of ulcerative colitis and other inflammatory bowel diseases.
The main objective of the study was to demonstrate release of polymer-bound PL-8177 in the lower gastrointestinal tract after oral administration. Top line data showed favorable pharmacokinetics, and demonstrated PL-8177 was released in the lower gastrointestinal tract, supporting oral administration of PL-8177 using the delayed release polymer formulation.
A secondary objective of the study was also met, demonstrating that PL-8177 is not systemically absorbed after oral administration. There was no intact PL-8177 or its metabolite detected in plasma after oral administration. The oral formulation was well tolerated and there were no adverse events observed.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!
"The results of this study support moving forward with development of polymer-bound PL-8177 to deliver drug to the lower gastrointestinal tract to treat ulcerative colitis and other inflammatory bowel diseases," said Dr. Carl Spana, President and Chief Executive Officer of Palatin Technologies. "Importantly, this study demonstrates that our oral, delayed-release polymer formulation of PL-8177 can deliver peptide to the diseased region of the bowel, without systemic uptake. The melanocortin receptor 1 is a novel target for treating ulcerative colitis and other inflammatory diseases, as it is present on the interior wall, or lumen, of the colon and lower gastrointestinal tract."
The lumen of the colon and lower gastrointestinal tract contains cells with receptors for melanocortin-1, which when activated by binding of PL-8177 can result in resolution of chronic inflammatory responses. The delayed release polymer formulation of PL-8177 is designed to protect the peptide until it reaches the lower gastrointestinal tract.
This open label study enrolled 24 subjects divided into 6 cohorts of 4 patients each. Blood, urine and feces samples were analyzed for total radioactivity and radiolabeled PL-8177 and its metabolite. The percentage of intact radiolabeled PL-8177 and its metabolite was measured at different timepoints following administration of a single oral microdose of polymer-bound radiolabeled PL-8177.
Evolving research suggests that the melanocortin receptor 1 (MC1r) system plays an important role in anti-inflammatory responses and immunoregulation, including resolution of innate pro-inflammatory immune responses. PL-8177 is Palatin's lead clinical development candidate for ulcerative colitis and other inflammatory bowel diseases. PL-8177, a selective MC1r agonist peptide, is a synthetic cyclic heptapeptide with demonstrated efficacy in animal inflammatory bowel disease models. PL-8177 is a potent agonist at human MC1r, with sub-nanomolar affinity binding and EC50 functional values.