arGentis Pharmaceuticals to commence human clinical evaluation of ARG301 oral altered peptide ligand

Nov 12 2009

arGentis Pharmaceuticals, LLC today announced that it will collaborate with the University of Tennessee Health Science Center (UTHSC) and the Veterans Affairs Medical Center of Memphis (VAMC) to initiate the first human clinical evaluation of an oral altered peptide ligand (APL), ARG301, in a Phase I study of Rheumatoid Arthritis patients. ARG301 is a synthetic peptide, which in animal studies appears to down regulate autoimmunity to Type II collagen (CII), a known autoantigen in RA. Investigators at the UTHSC and Memphis VAMC developed the therapy and have received a Clinical Merit Review Grant from the Department of Veterans Affairs to conduct the trial.

“Due to its unique mechanism of action and compelling preclinical data, we are hopeful that ARG301 will offer a novel therapeutic approach for rheumatoid arthritis,” said Tom I. Davis, II, Chief Executive Officer of arGentis. “In continuing our partnership with UTHSC and University of Tennessee Research Foundation, arGentis is very pleased to add this promising oral therapeutic consistent with our autoimmunity R&D approach.”

Research in animal models suggests APLs (Altered Peptide Ligands) are effective in preventing and ameliorating tissue-specific autoimmune diseases. Trials of APLs administered intravenously or subcutaneously in human autoimmune disease have had mixed results. None of these trials, however, incorporated a pre-selection step to test the ability in vitro of the APL, to down regulate Th1 response by patient’s peripheral blood mononuclear cells (PBMC) stimulated by a disease-specific autoantigen such as CII in RA patients.

In preclinical testing, mice susceptible to Collagen Induced Arthritis (CIA) bear a transgene for the human RA MHC susceptibility genes, DR1 or DR4. These mice appear to be resistant to CIA after oral administration of ARG301. Although the precise mechanism by which the specific peptide comprising ARG301 exerts its effect is not yet clear, the interaction of the APL/MHC complex with the TCR appears to play a key role in influencing the differentiation of naive T cells into effector cells.

Based on the experience in animals, oral administration of APLs to preselected “in vitro” responders should provide a nontoxic and highly defined therapy for humans with tissue-specific autoimmune diseases such as RA.

42 RA patients will be enrolled a Phase I Trial at the Memphis VAMC which will evaluate multiple ascending doses of ARG301 to be administered orally. The primary objectives of the trial will be to determine if one or more of the three doses of ARG301 given to Rheumatoid Arthritis patients will generate functional T regulatory cells and decrease immune reactivity to CII. The study will have 3 ARG301 treatment arms, each with 10 patients and a placebo arm of 12 patients. Patients will be enrolled who have demonstrated T cell immunity to CII and have an in vitro response to ARG301 at the screening visit. Patients will be randomized to one of the 4 arms, and each of the 3 ARG301 and placebo treatments will be given for 16 weeks.