Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) today announced data from preclinical studies of IMO-8400, demonstrating a novel mechanism of action that may be applicable to the treatment of systemic lupus erythematosus (SLE) and psoriasis. IMO-8400 is an inhibitor of specific Toll-like receptors (TLRs). The data were presented at the American Association of Immunologists (AAI) meeting being held in Boston, Massachusetts May 4-8, 2012.
“We are encouraged by the preclinical results with IMO-8400 as a novel approach for the treatment of lupus and other autoimmune disorders,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer. “The dose-dependent protection we see in the lupus-prone mouse model suggests that pharmacologic inhibition of TLR7, 8, and 9 with IMO-8400 may provide a therapeutic strategy to suppress many lupus disease-associated parameters, including autoimmune antibodies, multiple pro-inflammatory serum cytokines, and indicators of kidney damage.”
A characteristic of SLE is the production of antinuclear autoantibodies complexed with self-RNA or -DNA. These abnormal antibodies inappropriately activate TLR7, 8, and 9 and initiate immune responses that damage the body’s own tissues and organs, thereby releasing more self-RNA and DNA. The data presented at AAI demonstrate that inhibition of TLR7, 8 and 9 with IMO-8400 suppressed the cycle between autoimmune antibody production and tissue damage, leading to improved renal function in lupus-prone mice. No treatment-related side effects were observed in the mice from IMO-8400 treatment at the doses employed in the study.
Idera expects to submit an Investigational New Drug application for IMO-8400 to the FDA during the fourth quarter of 2012, and has selected lupus as the initial disease indication for clinical development.
The oral presentation entitled “IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in lupus-prone NZBW/F1 mice” was made on May 5
. In addition a poster presentation entitled “IMO-8400, a novel TLR7, TLR8, and TLR9 antagonist, inhibits disease development in mouse models of psoriasis” was presented at AAI on May 6
. In the poster presentation, data demonstrated that IMO-8400 suppressed lesion development and related immunological makers in mouse models of psoriasis.
In addition to the above presentations, a poster presentation entitled “Modification of immune activation in HIV-1 infected humanized mouse model using TLR7/9 antagonists” was given in the Vaccine and Immunotherapy session on Sunday, May 6
at 2:30 pm by investigators from the Ragon Institute of MIT, Massachusetts General Hospital, and Harvard Medical School in collaboration with Idera Pharmaceuticals.
These presentations are accessible on the Idera Pharmaceuticals website.