We are conducting preclinical studies with our melanocortin receptor-1 (MC1r) peptide drug candidates for a number of indications, primarily inflammatory disease-related and autoimmune indications. The MC1r is upregulated in a number of diseases, including inflammatory bowel disease, nephritis (inflammation of the kidneys), rheumatoid arthritis, ocular indications such as uveitis and dry eye, and dermatologic indications. We believe that MC1r peptides have an anti-inflammatory effect and can work to regulate the immune system and resolve pro-inflammatory responses.
Our MC1r peptide drug candidates are highly specific, with substantially greater binding and efficacy at MC1r than at other melanocortin receptors. In vitro safety studies have shown that our MC1r peptide drug candidates have no activity in a wide range of receptors, ion channels and kinases. Our MC1r peptide drug candidates typically have a half-life in animal models of greater than two hours.
Animal studies that we have conducted with our MC1r peptides have shown positive results in experimental models of inflammatory bowel disease, uveitis and nephritis. We are continuing to conduct studies on a number of different indications.
PL-8177, Our Lead Inflammatory Disease Product Candidate
Our lead inflammatory disease product candidate for inflammatory bowel diseases is a synthetic peptide we developed with the code name PL-8177.
PL-8177, a selective MC1r agonist peptide, is our lead clinical development candidate for inflammatory bowel diseases, with potential applicability for a number of other diseases. We filed an Investigational New Drug application on PL-8177 in late 2017 and have completed subcutaneous dosing of human subjects in a Phase 1 single and multiple ascending dose clinical safety study, with data expected in the fourth quarter of calendar year 2018. We anticipate starting a clinical study with oral dosing of PL-8177 in human subjects in the second half of calendar year 2018, with data expected in the first half of calendar 2019.
We presented a poster on preclinical studies with an oral formulation of PL-8177 at the 2018 Keystone Symposia on “The Resolution of Inflammation in Health and Disease” held March 24-28, 2018. The poster is here. The data demonstrates that the oral formulation protected PL-8177 from degradation in the stomach and small intestine, and delivered PL-8177 to the large intestine and colon over an extended period. In addition, orally administered PL-8177 had a significant effect on resolving inflammation in a rat bowel inflammation model.
PL-8177 has demonstrated efficacy in preclinical models for autoimmune uveitis, inflammatory bowel disease and nephritis. Preclinical animal studies show PL-8177 suppresses the physiologic activity of inflammatory challenges, resulting in the reduction of a number of inflammatory cytokines.
We have another synthetic peptide we developed, with the code name PL-8331, which is selective for both the melanocortin receptor-1 and melanocortin receptor-5. This peptide is under preclinical evaluation in ocular inflammatory models, and if results are favorable, anticipate filing an Investigational New Drug Application and initiating clinical trials for the treatment of dry eye disease in the second half of calendar year 2019.