PI-2301 Peptide Copolymer
Rheumatoid arthritis is characterized by autoreactive CD4+ T helper cells which are destructive to the synovium.
It is known that peptides and peptide copolymers composed of certain amino acids are able to affect the activity of the CD4+ T-cells involved in the development and progression of several autoimmune diseases. PI-2301 represents a new generation of peptide copolymer that is expected to have superior efficacy & convenience profile compared to current immunomodulating agents for treatment of multiple sclerosis, and may be beneficial for rheumatoid arthritis.
Mechanism of Action
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, this mechanism modulates the immune system from an inflammatory state to a regulatory state.
Preclinical Development
Preclinical studies conducted in a transgenic, double knock-in model of the most severe form of human rheumatoid arthritis have demonstrated the efficacy and dose response 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 demonstrated a dose-related decrease in disease score, correlated with a reduction in anti-type II collagen antibodies and histopathology.
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 rheumatoid arthritis patients once proof of principle is established in other diseases, such as multiple sclerosis.
