Research: Drug Discovery Platforms: TLR

Toll-like Receptors

Toll-like receptors, TLRs, are a family of immune system receptors.  

TLRs 3, 7, 8, and 9 are expressed in endosomes within specific immune system cells. TLR9 is a receptor that is shown to recognize patterns characteristic of bacterial DNA. TLRs 3, 7, and 8 are receptors that recognize patterns characteristic of viral RNA. Extensive publications report that TLR-mediated immune responses provide scientific rationale for treatment of a broad range of diseases, including cancer, infectious diseases, autoimmune and inflammatory diseases, respiratory diseases, hematologic oncology, and for use as vaccine adjuvants.

Agonists of Toll-like Receptors

Idera has created synthetic RNA and DNA-based compounds which activate immune responses by interacting with each of TLR3, 7, 8, and 9, and are referred to as TLR agonists.   Studies of these agonists in various preclinical models have shown that the immune responses mediated through TLRs 3, 7, 8, and 9 can be differentiated by changes in the structure and chemical composition of the compounds, thereby allowing selection of a drug candidate appropriate for each specific intended therapeutic indication. Our pipeline of candidates includes IMO-2055, a TLR9 agonist for the treatment of cancer, the IMO-2134, a TLR9 agonist for the treatment of respiratory diseases, and the IMO-4200, a dual TLR7/8 Agonist for hematologic oncology.

Antagonists of Toll-like Receptors

Idera has also created compounds which block specific TLRs, thereby inhibiting immune responses.  This class of compounds is referred to as TLR antagonists.  The ability to block specific TLR-mediated immune responses is potentially useful in the treatment of in conditions such as autoimmune and inflammatory diseases, where TLRs are shown to play a role in generating inappropriate immune responses. Our pipeline of candidates includes IMO-3100, an antagonist of TLRs 7 and 9 in clinical development for the treatment of psoriasis, and IMO-8400, an antagonist of TLRs 7, 8, and 9 in development for the treatment of lupus.