The TLR7 Pathway – Novel Mechanism Ideally Suited to Treat Cancers
TLR7 agonists engage a variety of antitumor responses, the most important of which are initiated by activation of plasmacytoid dendritic cells (pDCs). The activation of pDC’s mediates direct killing of tumor cells by the production of soluble factors including Type I and III IFN’s as well as therapeutic engagement of NK cells and other elements of the antitumor innate immune response. Activated pDC’s also drive a coordinated adaptive immune response resulting in the activation of B cells, cytotoxic T cells and the downstream differentiation of Th1 cells which is critical to long-term disease control.
PRTX007: Clinical Validation of Primmune’s TLR7 Agonist
PRTX007 (prodrug) is Primmune’s lead clinical development candidate which upon oral administration systemically delivers PRX034, a tuned TLR7 agonist. PRTX007 administration uniquely activates pDCs, leading to a systemic immune poly-IFN response without stimulating production of NF-κB driven proinflammatory factors like IL-6, TNFα or IL-1β. Activated pDCs directly deliver interferons to target cells by paracrine transfer; functionally equivalent to administering a cocktail of all Type I/III IFN while avoiding the associated side effects and adverse events.
Preclinical data for PRTX007 have demonstrated the systemic distribution and activation of target cells and the ability to maintain immune pressure without activating proinflammatory cytokines. Published interim clinical data from the PRTX007 first-in-human (FIH) study in healthy volunteers demonstrates:
- A favorable safety profile; no apparent overlapping mechanistic toxicity with that of known checkpoint inhibitors
- Dose-dependent systemic exposure and activation of the innate immune response without production of proinflammatory cytokines
- Breadth of immune induction and a coordinated downstream adaptive immune response
Click here for publications highlighting Primmune’s published clinical data.
Primmune’s Therapeutic Focus
PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearance of pre-cancerous cervical lesions caused by human papillomavirus (HPV).
By combining PRTX007 with checkpoint inhibitors, Primmune is seeking to improve overall response rates and treatment durability. Because PRTX007 is orally delivered and systemically distributed, it has the advantage of potentially accessing multiple tumor types as well as metastatic disease. Additionally, PRTX007 was designed to maintain constant immune pressure without driving immune exhaustion or a proinflammatory response and therefore will be studied as a potential long-term treatment.
PRTX007 is also suited as an early monotherapy treatment for cervical pre-cancerous lesions given the anti-viral and anti-tumor aspects of the TLR7 pathway via pDC activation.
Our team is committed to the invention of new medicines to treat people suffering from cancer and viral infections and to create substantial value for our investors and partners. We have comprehensive experience in the science and business of drug discovery, development, and commercialization.
Primmune Therapeutics, Inc.
2333 State Street, Suite 203
Carlsbad, CA 92008