Publications
Preclinical and Clinical Development of a Second Generation Peptide Copolymer for the Treatment of Multiple Sclerosis
Federation of Clinical Immunology Societies Meeting 2008
Joseph Kovalchin1, Jeffrey Krieger1, Ingrid Dufour1, Kathy Collins1, Michelle Genova1, Michael Augustyniak1, Allyson Masci1, Kristen Rafuse1, Alain Patat2, Uday Patel1, Edward Mascioli1, Eric Zanelli1 1Peptimmune, Inc. 64 Sidney Street, Suite 380, Cambridge, MA-02139, USA2Biotrial S.A., rue Jean-Louis Bertrand, 35000 Rennes, France PI-2301 is a novel compound in a class of autoimmune therapeutics called peptide copolymers. Copolymers are random mixtures of peptide sequences comprised of limited numbers of amino acids. Copaxone® is a copolymer which has been approved as a primary treatment for Relapsing Remitting-Multiple Sclerosis (RR-MS). PI-2301, like Copaxone, is an immunomodulator which binds MHC Class II molecules and induces a TH2 response characterized by the activation and expansion of T-cells and monocytes producing IL-4, IL-5, IL-10, IL-13 and CCL22. This regulatory response is believed to interfere on the expansion of autoreactive TH1/TH17 cells. PI-2301 has shown superior efficacy as compared to Copaxone in experimental allergic encephalomyelitis (EAE), an animal model which resembles multiple sclerosis, in both daily and weekly dosing regimens. We now report the results of a Single Ascending Dose, first-in-man study evaluating the safety of PI-2301 in healthy, male adult volunteers. Fifty-six subjects (eight cohorts of seven individuals; 5 active and 2 placebo) were given a single subcutaneous injection of PI-2301. Design of this clinical study was in accordance with new recommendations as defined in the Duff report and recent CHMP guidelines issued in July 2007. The first dose was 100-fold below a well-defined Minimal Anticipated Biological Effect Level (MABEL) and 50,000-fold below the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal species. Read-outs included safety, pharmacokinetics, T-cell recall and antibody response to PI-2301, serum cytokines and chemokines. This study represents the first step in the development of an improved peptide copolymer with immunomodulatory properties for the treatment of multiple sclerosis.
