The Importance of Plasmacytoid Dendritic Cells (pDCs)
Plasmacytoid dendritic cells are immune cells that are activated by the presence of viral infections or tumor cells. The detection of viral infections or tumor cells is carried out by a narrow set of proteins, including toll-like receptors (TLRs) such as TLR7, which activate pDCs. Once activated, pDCs mediate 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 cytotoxic T cells and the downstream differentiation of Th1 cells which is critical to long-term disease control.
Systemic activation of pDCs is especially important as this provides a benefit to cancer treatment in two important ways: first by reversing immunosuppression by exhausted pDCs in the tumor microenvironment and secondly by initiating surveillance by activating circulating pDCs.
PRTX007: Clinical Validation of Primmune’s TLR7 Agonist
PRTX007 is a tuned TLR7 agonist and Primmune’s lead clinical development candidate. PRTX007 is administered orally and uniquely activates pDCs, leading to a systemic immune poly-IFN response without stimulating systemic 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 systemic 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 – Virally-Mediated Cancers
The global burden of HPV-caused cancers is significant and includes cervical, vaginal, vulvar, penile, anal and oropharynx cancers. The U.S. incidence of oropharyngeal cancers alone is >54,000 new cases per year. More than 70% of oropharyngeal cancers are caused by HPV and while vaccination has been helpful, it’s not expected to reverse the increasing rates of oropharyngeal cancers until well after the year 2045.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. The U.S. incidence of HCC is >47,000 new cases per year and is expected to grow 55% by the year 2050. The primary cause of HCC in the U.S. is Hepatitis C (HCV). While there is a treatment for HCV, 75% of individuals who have HCV are unaware that they have it and only 1 in 3 individuals infected with HCV have been cured in the 10 years since direct-acting antiviral treatment has been available. Hepatitis B (HBV) is also a cause of HCC despite the availability of the HBV vaccine since the early 1980’s.
PRTX007 is being rapidly advanced towards clinical trials for HPV-caused oropharyngeal cancer and HCC.
Our team is committed to the invention of new medicines to treat people suffering from cancer 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