Idera Pharmaceuticals presents IMO-3100 TLR antagonist mechanism of action data at Keystone conference

Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today presented data on the mechanism of action of IMO-3100, an antagonist of Toll-like Receptor (TLR) 7 and TLR9, in a preclinical primate model at the Keystone Symposia conference “Tolerance and Autoimmunity” being held February 21-26 in Taos, New Mexico. Idera is developing IMO-3100 for the treatment of autoimmune diseases. The presentation entitled “IMO-3100, a novel antagonist, suppresses TLR7- and TLR9-mediated immune responses in non-human primates” was made by Idera scientists. The data presented showed that subcutaneous administration of IMO-3100 suppressed TLR7- and TLR9-mediated immune responses in primates, reducing production of cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-alpha (IFN-α), IP-10, and IL-6.

“IMO-3100, a novel antagonist, suppresses TLR7- and TLR9-mediated immune responses in non-human primates”

“We are very encouraged to have demonstrated the mechanism of action for IMO-3100 in the primate model, and we have incorporated a similar pharmacodynamic evaluation in our Phase 1 clinical trial in addition to safety assessment,” said Tim Sullivan, Ph.D., Vice President, Development Programs. “We expect that the pharmacokinetic and pharmacodynamic results from the ongoing rising single-dose clinical trial will facilitate the initiation of subsequent clinical trials of IMO-3100 in autoimmune diseases.”

In the studies presented today, the mechanism of action of IMO-3100, which is inhibition of TLR7- and TLR9-mediated immune responses, was evaluated in non-human primates. IMO-3100 was administered to cynomolgus monkeys by subcutaneous injection. Blood samples were taken prior to IMO-3100 administration and at 24-hour intervals through 96 hours after dosing and at one week after dosing, using blood collection sites remote from the injection site. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples and cultured in the presence of TLR7 or TLR9 agonists. Cytokines and chemokines in supernatants from the cell cultures were measured by multiplex assay. Cytokine and chemokine induction in PBMC cultures was compared between samples collected prior to and after IMO-3100 dose administration. Results demonstrated that IMO-3100 inhibited induction of cytokines and chemokines, including TNF-α, IFN-α, IP-10, and IL-6. This inhibition was dependent on both the dosage of IMO-3100 administered and the time after administration of IMO-3100. IMO-3100 inhibition was specific to TLR7 and TLR9, with no significant reduction in cytokine levels inducted in PBMCs cultured with TLR4 or TLR8 agonists.