— PRTX007 demonstrated a favorable safety profile for all analyzed cohorts with no serious adverse events (SAEs) observed —
— Well-controlled activation of innate and adaptive immune response observed without increases in proinflammatory factors —
— Data support suitability of PRTX007 for investigation as a key component of combination therapy for curative treatment of chronic hepatitis B virus (HBV) infection —
SAN DIEGO, November 10, 2023 – Primmune Therapeutics, a biotech company harnessing the power of the innate immune system, today presented clinical data from its first-in-human, Phase 1 study of PRTX007, an orally administered prodrug of a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist, at the 2023 American Association for the Study of Liver Diseases (AASLD) Annual Meeting (The Liver Meeting). The data presented highlight the suitability of PRTX007 for investigation as a combination therapy for curative treatment of chronic hepatitis B virus (HBV) infection.
This was a first-in-human, phase 1, single-center, prospective, randomized, double-blind, placebo-controlled study of 9 single-ascending dose (SAD) cohorts and 4 multiple-ascending dose (MAD) cohorts of PRTX007 administered orally every other day (QOD) to adult healthy volunteers. In addition to the primary objective of assessing the clinical safety and tolerability of PRTX007, the study was designed to evaluate the pharmacokinetics and pharmacodynamics of PRTX007 and PRX034, and identify the specific active dosing range for use in future infectious viral disease studies via pharmacodynamic and immune markers.
Data show that PRTX007 demonstrated a favorable safety profile in all of the analyzed cohorts with no serious adverse events (SAEs) observed. QOD dosing was shown to activate the innate and adaptive immune responses, with significant increases in CD8+ T-cell and NK cell activation observed from pretreatment to end of dosing in all healthy volunteers. There were no clinically relevant increases in expression or circulating levels of proinflammatory cytokines observed for any dose range in the study.
“We are encouraged by the results of this Phase 1 study which demonstrate the safety and tolerability of PRTX007 administration in healthy volunteers. These results should translate to treatment of patients with acute and chronic viral diseases, including chronic HBV infection, and support further exploration of PRTX007 in future infectious viral disease studies,” said James Appleman, Ph.D., Co-founder and Chief Scientific Officer at Primmune Therapeutics. “Well-controlled, coordinated activation of the innate and adaptive immune response was observed without increases in proinflammatory factors, signaling the potential of PRTX007 to be a key component of a combination therapy resulting in a functional cure of chronic HBV infection.”
Title: Clinical validation of an orally-delivered, systemically activated TLR7 agonist to boost host immune response to chronic viral diseases, including hepatitis B virus
Presenting Author: Curtis L. Scribner, M.D.
Poster ID: 1463-C
Presentation Date and Time: Friday, November 10 – 12:00 PM – 1:00 PM ET
Location: Hynes Convention Center, Hall C (second floor)
Additional highlights from the poster presentation include:
- PRTX007 demonstrated a favorable safety profile when administered orally to all 9 SAD and 4 MAD cohorts tested. Most AEs were mild and not dose-related, with no instances of dose modification or discontinuation due to treatment-related AEs throughout the study. The most common drug-related AE was headache, seen across both treated and placebo groups independent of dose.
- Repeated oral QOD doses of PRTX007 increased the magnitude of antiviral mRNA response. The short half-life of PRTx007 enables a targeted, short pulse of exposure to the active agonist without accumulation of the drug between doses.
- PRTX007 demonstrated well-controlled expression of interferon-stimulated genes (ISGs) independent of dose, without significant increases in circulating IFNs. There was no increase in expression or circulating levels of proinflammatory cytokines (e.g., TNFα, IL-6, IL-1β).
- CD8+ T cells and NK cell activation (CD38+ markers) increased markedly from pretreatment to end of dosing in all HVs.
PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 administration uniquely activates plasmacytoid dendritic cells (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. Conceptually, this is equivalent to administering a therapeutically effective cocktail of all Type I/III IFNs while avoiding the associated side effects and adverse events. Furthermore, PRTX007 administration leads to systemic activation of anti-tumor effector CD8+ T cells and NK cells.
About Primmune Therapeutics
Primmune Therapeutics is a clinical-stage biotech harnessing the power of the innate immune system by developing small molecule, orally administered toll-like receptor 7 (TLR7) agonists. For more information, please visit https://www.primmunerx.com/.