Slide Harnessing Innate Immunity to Treat Cancer and Viral Infections Primmune Therapeutics is developing small molecule, orally-administered toll-like receptor 7 (TLR7) agonists to attack tumors and potentiate adaptive cancer immunotherapies, such as checkpoint inhibitors, to improve overall response rates and treatment durability. The Company is also developing TLR7 agonists that are suited for prevention and treatment of viral infections as monotherapy or in combination with direct-acting antivirals. Harnessing Innate Immunity to Treat Cancer and Viral Infections Primmune Therapeutics is developing small molecule, orally administered toll-like receptor 7 (TLR7) agonists to attack tumors and potentiate adaptive cancer immunotherapies, such as checkpoint inhibitors, to improve overall response rates and treatment durability. The Company is also developing TLR7 agonists that are suited for prevention and treatment of viral infections as monotherapy or in combination with direct-acting antivirals.

Cancer Science

Recent advances in cancer immunotherapy have resulted in medications that have profound benefit to some patients. Unfortunately, most cancer patients are relatively unresponsive to single agents such as PD-(L)1 checkpoint inhibitors. Literally hundreds of clinical studies are currently being conducted to identify therapeutic combinations that improve the response rate. The vast majority of these immunotherapy combinations affect the adaptive immune system; this represents one arm of the immune system. We focus on the second arm, the innate immune system. It is well-recognized that one of the next big breakthroughs in cancer immunotherapy is likely to involve combinations of agents that activate both innate and adaptive immunity.

Cancer Therapeutics

We are developing an orally administered toll-like receptor 7 (TLR7) agonist for systemic activation of innate immunity. The TLR7 receptor is expressed on plasmacytoid dendritic cells (pDCs) and B-cells. Anti-tumor mechanisms engaged by a TLR7 agonist include:

 

  • Activation of pDCs to produce cytokines and chemokines that up-regulate general cellular responses
  • NK (natural killer) cell activation
  • CTL (cytotoxic T-cell or CD8+ T-cell) activation
  • Enhanced antibody-mediated killing of tumor cells via antibody-dependent cellular cytotoxicity (ADCC), particularly with therapeutic mAbs as well as endogenous antibodies
  • Increase in proliferation and activation of B-cells

Current Challenge

In general, candidate drugs from other leading programs targeting innate immunity must be administered via intratumoral injection. This results in limitations that are circumvented by an orally delivered, systemically distributed TLR7 agonist. Advantages to our approach include an ability to:


  • Access all solid
    tumors


  • Treat blood
    cancers


  • Address all metastatic
    disease


  • Stimulate B-Cell proliferation
    and activation

    most innate immunity approaches do not have an effect on B-Cells


  • Flexibility in dosing

    frequent dosing is difficult with intratumoral injections

Currently there are no other TLR7 agonists approved or in development for cancer therapy that are acceptable for systemic delivery, a key requirement for the treatment of most solid and liquid tumors.

TLR7 Agonists for Acute and Chronic Viral Infections

We have continued our discovery program directed at the creation of new medicines that act via TLR7 agonism to treat acute and chronic viral infections. The role of TLR7 in both alleviating established infections and preventing new infections is well-recognized. For example, acute viral load decreases in excess of 1log10 were observed when patients with chronic HCV were dosed with the TLR7 agonist prodrug ANA773 (Anadys Pharmaceuticals, Inc). Further, ANA773 was safe and well-tolerated in long-term dosing in the clinic. TLR7 agonists are currently in clinical development for the treatment of viral diseases as diverse as chronic hepatitis B and HIV. Primmune’s compounds are expected to have substantial advantages with respect to potency, safety, tolerability and convenience while fully maintaining efficacy when compared to other TLR7 agonists.

Team

Our team is committed to the invention of new medicines to treat people suffering from cancer and viral infections, and to the creation of substantial value for our investors and partners. We have comprehensive experience in the science and business of drug discovery and development.

Contact Us

JLABS San Diego
3210 Merryfield Row
San Diego, CA 92121