Agonists

Agonists of TLRs are compounds that stimulate, or “turn on,” the immune system. Natural agonists for TLR9 are components of DNA that are common to bacteria and viruses. Natural agonists for TLRs 7 and 8 are patterns of RNA found in viruses. Following recognition of their natural DNA and RNA agonists, TLRs 7, 8, and 9 each initiate a different cascade of protective immune responses.

Idera has used its extensive nucleic acid chemistry experience to create DNA and RNA based compounds which have improved drug-like properties over the natural TLR agonists. Idera’s approach has led to the discovery of a portfolio of novel compounds that mimic the natural agonists of TLRs 7, 8, and 9. These novel DNA and RNA compounds contain chemical modifications and unique structural components. Studies of these novel compounds in various preclinical models have shown that the immune responses mediated through TLRs 7, 8, and 9 can be modulated in ways potentially appropriate for various applications.

Using this approach, Idera has identified IMO-2055 and IMO-2125 as lead candidates, and continues to create novel compounds to support additional internal programs and for external collaborations.

Idera’s TLR Agonist Programs
Idera is currently developing the following TLR agonists:

TLRs 7, 8, and 9 function by detecting the DNA or RNA of pathogens, including bacteria and viruses as shown in the illustration above (1). When the TLR detects this genetic material, it signals through key factors in the immune cells to initiate immune responses (2). The immune response begins with a release of cytokines and other components of the innate immune system (3). Innate immune responses are immediate general disease-fighting actions. The TLR-mediated response also stimulates adaptive immune responses. Adaptive immune responses include generation of long-term memory responses to defend against the same infection or disorder in future exposures.