A novel, synthetic TLR7/8 agonist demonstrates monotherapy efficacy and synergy with anti-PD-1 in syngeneic mouse tumor models

Abstract

Abstract Cancer is the second leading cause of death in the United States, with more than half a million Americans succumbing to this disease every year. To date, immunotherapies such as anti-PD-1 and anti-CTLA-4 have shown some advancement toward treating certain cancer types, but efficacy is typically reserved for a small subset of cancer patients. Recent clinical trials have shown that melanoma and renal cell carcinoma patients had some of the highest rates of response to checkpoint treatment, but even then, the rate of response was only 20% and 22%, respectively. Furthermore, immunotherapies can lead to severe adverse reactions due to their ability to activate non-specific immune responses. Inimmune has developed and tested a novel TLR7/8 agonist as an immunotherapy for cancer. In vivo mouse studies demonstrated that IV treatment with our novel, synthetic TLR7/8 agonist in combination with anti-PD-1 resulted in increased efficacy in eliminating tumors or slowing tumor growth over anti-PD-1 treatment alone in B16F10 and MC38 tumor models in C57BL/6 mice. Furthermore, lead formulations of our novel, synthetic TLR7/8 agonist demonstrated efficacy as a monotherapy in BALB/c mice inoculated with a highly tumorigenic Lewis Lung Carcinoma (LLC) cell line. Taken together, our data indicate that this novel, synthetic TLR7/8 agonist was tolerated systemically, functioned as a monotherapy, and synergized well with anti-PD-1 treatment in various mouse syngeneic tumor models. As we move this compound to Phase 1 clinical trials, these data suggest that our TLR7/8 agonist can be dosed safely as a monotherapy or in combination with checkpoint therapy and may drive efficacious anti-tumor responses in humans.