PI-2301 Peptide Copolymer
Certain peptides and peptide copolymers composed are able to affect the activity of the CD4+ T-cells involved in the development and progression of multiple sclerosis.
PI-2301 is a second-generation peptide copolymer from a similar compound class as Copaxone®, and it is expected to have superior efficacy and convenience profile compared to current immunomodulating agents for the treatment of multiple sclerosis.
Mechanism of Action
PI-2301 binds to MHC 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.
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 has initiated its first repeat-dose study in multiple sclerosis patients in Q2/2008.
Discovery of PI-2301
- Using crystallography of MHC Class II variants associated with MS and autoimmune disease
- Substitution of amino acids into known peptides and peptide copolymers for better binding
- Optimizing molar ratios of amino acids for enhanced binding and immunogenecity
- Testing binding to MHC Class II complex on the surface of antigen-presenting cells and T-cells from MS patients
Opportunity
PI-2301 has the opportunity to replace Copaxone®, the world's leading first–line therapy for the treatment of MS, which currently has sales nearing $2 billion and growing at a 24% CAGR. Two recent head-to-head studies comparing Copaxone®, beta-interferons [Betaseron® (Bayer Schering, and Rebif® (Merck Serono) validate Copaxone's® superior safety/tolerability profile while preserving efficacy. One liability of Copaxone® is its daily subcutaneous-injection schedule. PI-2301 has been designed as a weekly injection, improving patient convenience and compliance. PI-2301 has been shown to be more efficacious than Copaxone® in preclinical models of MS called experimental autoimmune encephalomyelitis (EAE).
