PI-2301 Peptide Copolymer
Crohn’s disease is characterized by autoreactive CD4+ T helper cells that are destructive to the GI tract. PI-2301 may affect the activity of the CD4+ T-cells involved in the development and progression of Crohn’s disease.
Mechanism of Action
PI-2301 is a second-generation peptide copolymer from a similar compound class as Copaxone®, and is expected to have superior efficacy and convenience profile compared to current immunomodulating agents for the treatment of multiple sclerosis, and may be beneficial in Crohn’s disease.
PI-2301 binds to MHC Class II molecules on monocytes, macrophages, and dendritic cells both subcutaneously and in circulation. This binding induces a differentiation of these antigen-presenting cells which leads to an expansion of immune regulatory Th2 and T-regulatory cells. This expansion of Th2/Treg cells controls and minimizes the autoimmune inflammatory Th1/Th17 cell populations. In short, PI-2301 modulates the immune system from an inflammatory state to a regulatory state.
Preclinical Development
Preclinical studies conducted in the DSS model have demonstrated the efficacy of PI-2301 to ameliorate disease and disease progression. By comparison, Copaxone was not effective in this model at any dose. PI-2301 has been optimized for weekly administration and studies have demonstrated dose response and related pharmacokinetics in disease models with therapeutic dosing regimens.
Clinical Development
Peptimmune has completed its first clinical trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PI-2301. The Phase I single-ascending dose, double-blind, placebo-controlled randomized study involved fifty-six healthy volunteers who received the drug in eight escalating-dose cohorts. All doses were safe and well tolerated, and there were no serious adverse events. Pharmacodynamic assays demonstrated evidence of immune exposure consistent with the pharmacologic mechanism of action for PI-2301, and dose-related pharmacokinetics were observed. The Company plans to initiate studies in Crohn’s disease patients once proof of principle is established in other diseases, such as multiple sclerosis.
