TLR8 Product Pipeline
VentiRx's lead investigational drug, motolimod, is a TLR8 agonist designed to activate a patient's own immune system by directly activating myeloid dendritic cells, monocytes and natural killer cells. This activation results in the production of a high level of mediators known to orchestrate the integration of both the innate and adaptive anti-tumor responses to a variety of cancers. The addition of motolimod to some standard-of-care anticancer agents (chemotherapy, monoclonal antibodies) may augment the anti-tumor response (Lu, et al. Clin Cancer Res. 2012; Stephenson, et al. Cancer Immunol. Immunother. 2013). Over 75 patients have been treated with motolimod in Phase 1 studies. Two large randomized Phase 2 trials in ovarian cancer and in squamous cell cancer of the head and neck are currently enrolling patients.
VTX-1463 is a TLR8 agonist administered intra-nasally for the treatment of seasonal and perennial allergies. Three Phase 1 studies have been completed in more than 150 patients. A randomized, placebo-controlled Phase 1b clinical trial in adult atopic patients showed evidence of clinical benefit. There was a significant improvement compared to placebo in the primary efficacy endpoints of Total Nasal Symptom Score (Friedrich Horak, Investig. Drug (2011) 20(7); 981-986).
Activation of TLR8 on monocytes and myeloid dendritic cells triggers an inflammatory response. This response modulates the adaptive cellular immune response via the production of interleukin-12 (IL-12). TLR8 expression and function has been implicated in various human autoimmune diseases including rheumatoid arthritis (Sacre S, et al. J of Immun 2008; 181:8002–8009) and inflammatory bowel disease (Saruta M, et al. Inflamm Bowel Dis 2009; 15:321–327).