arGentis Acquires Rights to Rheumatoid Arthritis Therapy Entering Phase I Clinical Trial

MEMPHIS, Tenn.--(BUSINESS WIRE)--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.

“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.”

“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.

About ARG301

The altered peptide ligand ARG301 is an oligopeptide derived from human CII sequence with substituted amino acids that binds to the MHC class II and interacts with the T cell receptor. ARG301 acts to change the cytokine profile from Th1 to Th2. Preclinically, DR1 or DR4 transgenic mice treated with oral or parenterally administered ARG301 were protected from arthritis induced by CII immunization. Short term toxicity studies using 100x the maximal human dose of ARG301 on a weight basis in mice did not cause any detectable toxicity. ARG301 is anticipated to have an exceptionally good safety profile in the clinic. To prove concept, ARG301 will eventually be evaluated in a broader trial of Rheumatoid Arthritis patients.

About Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and is the most common form of inflammatory arthritis. RA most often affects the smaller joints, such as those of the hands and/or feet, wrists, elbows, knees, and/or ankles. The cause of RA is not known but usually develops between 30 and 50 years of age. Although there is no cure for RA, the disease can be controlled in most people. Early, aggressive therapy to stop or slow down inflammation in the joints can prevent or reduce symptoms, joint destruction and deformity.

RA has a significant impact on both individual lives and society, including:

According to the Centers for Disease Control and Prevention (CDC), arthritis and other rheumatic conditions are the leading cause of disability in the U.S.,
3 million RA sufferers in the U.S.,
2.2 million are women,
U.S. incidence expected to increase to 5.8 million in the U.S. by 2013,
According to Johns Hopkins, disability is higher among patients with rheumatoid arthritis, with 60 percent being unable to work 10 years after disease onset,
People with rheumatoid arthritis have an increased risk of mortality or death rate compared to the general population, living 10-15 years less than healthy counterparts.

About Veterans Affairs Medical Center

The Department of Veterans Affairs Medical Center is affiliated with the University of Tennessee Health Science Center. Since 1922, the Memphis VAMC has been improving the health of the men and women who have so proudly served our nation with services available to more than 196,000 veterans living in a 53-county area of western Tennessee, northern Mississippi and northwest Arkansas.

About arGentis Pharmaceuticals

arGentis Pharmaceuticals is a privately-held diversified biopharmaceutical company dedicated to the licensing, development and commercialization of novel classes of therapies to treat chronic diseases in autoimmunity and ophthalmology. arGentis’ drug R&D programs are focused on treating underlying mechanisms of inflammatory conditions through utilization of oral and transdermal compounds. With its experienced management team, world-class scientists and advisors, arGentis is well-positioned to capitalize on its extensive portfolio of more than 50 patents and applications.