공시 • Nov 26
Palatin Technologies, Inc. Announces Completion of Patient Enrollment in Phase 2 Study of Orally Administered Melanocortin Agonist PL8177 in Ulcerative Colitis
Palatin Technologies, Inc. announced the completion of enrollment in its Phase 2 Study of PL8177, a potent melanocortin-1 receptor (MC1R) agonist, in ulcerative colitis (UC). The study is evaluating the safety, tolerability, efficacy, pharmacokinetics, and biomarkers of orally administered PL8177 in adult patients with active UC. The last patient visit is expected to occur in the first quarter of 2025, with topline data expected shortly thereafter. Ulcerative colitis is a form of inflammatory bowel disease (IBD) that causes inflammation in the digestive tract and can result in damage to the colon lining. Patients often experience a range of unpredictable symptoms that impact their daily lives, such as abdominal pain, bloody stool and urgency to use the bathroom. The disease course varies between patients, and in some cases can lead to surgery or complications, including cancer or death. Orally administered PL8177 targets melanocortin-1 receptors on the luminal surface of colon epithelial cells. In a Phase 1 clinical study, the oral formulation successfully demonstrated sustained delivery of PL8177 to the lumen of the colon with no systemic exposure. The Phase 2 PL8177 study is a multi-center, randomized, double-blind, placebo-controlled, adaptive design, parallel group of PL8177, with once daily (QD) oral dosing in adult UC subjects for 8 weeks. The study was originally designed to enroll up to 28 adult subjects with active UC from multiple sites, with an interim analysis planned after completion of 12-16 subjects. Due to the strategic decision to out-license the UC program at an earlier stage, Palatin decided to end enrollment after 13 subjects. The efficacy evaluations and endpoints are in line with the latest FDA Draft Guidance for Industry: Ulcerative Colitis: Developing Drugs for Treatment (April 2022), including the primary efficacy endpoint measurement, the Mayo Endoscopic Subscore, which evaluates the level of disease in the colon mucosa. Additional trial information, including inclusion and exclusion criteria, can be found at https://clinicaltrials.gov/via the identifier NCT05466890. The Company's Phase 2 trial in UC builds upon presented preclinical data from a series of oral PL8177 dose-ranging studies in the dextran sulfate sodium (DSS) colon inflammation model, which showed significant improvements in inflamed colon health, including relative increases in colon cells needed for a healthy colon. PL8177 treatment showed clear evidence of resolving pathological inflammation by repolarizing colon macrophages from a pro-inflammatory to a pro-inflammation resolving state. The melanocortin receptor ("MCR") system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function. There are five melanocortin receptors, MC1R through MC5R. Modulation of these receptors, through use of receptor-specific agonists, which activate receptor function, or receptor-specific antagonists, which block receptor function, can have medically significant pharmacological effects.Many tissues and immune cells located in the eye (and other places, for example the gut and kidney) express melanocortin receptors, empowering their opportunity to directly activate natural pathways to resolve disease inflammation. 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-1 receptor (MC1R), with sub-nanomolar affinity binding and EC50 functional values. Palatin data demonstrates that their oral formulation of PL8177 was protected from degradation in the stomach and small intestine of humans and delivered to the 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 1.25 million individuals in the United States are affected by ulcerative colitis, with over 350,000 diagnosed with moderate-to-severe disease.¹ 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.