On April 18, 2023 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and for the clearance of human papillomavirus and related pre-cancerous cervical lesions, reported new clinical data from a first-in-human, Phase 1 study evaluating PRTX007, an orally administered prodrug of a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida (Press release, Primmune Therapeutics, APR 18, 2023, View Source [SID1234630257]).
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The study was a first-in-human, Phase 1, single-center, prospective, randomized, double-blind, placebo-controlled study with 9 single-ascending dose (SAD) cohorts and 4 multiple-ascending dose (MAD) cohorts where PRTX007 was administered orally to adult HVs. In addition to assessing the clinical safety and tolerability of PRTX007, the study was designed to evaluate the pharmacokinetics of PRTX007 and identify the specific active dosing range for use in future cancer studies.
Consistent with interim results from the Phase 1 study, data show that PRTX007 was well-tolerated and expressed a favorable safety profile in all of the analyzed cohorts, with no serious adverse events (AEs) or AEs at or above grade 3. Every other day (QOD) dosing in the 750mg cohort demonstrated stable systemic induction of the innate and adaptive immune responses, with significant increases in CD8+ T cells and NK cell activation (CD38+ markers) observed from pretreatment to end of dosing in all HVs. There were no systemic increases in proinflammatory factors observed for any dose range in the Phase 1 study. Both the clinical characteristics and unique pattern of immune induction by PRTX007 support its use in combination with immune checkpoint inhibitors.
"These Phase 1 results set the stage for PRTX007 to enable long-term continuous immune induction in combination with other therapeutic modalities including checkpoint inhibitors and as a single agent," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "PRTX007 was shown to activate innate and downstream adaptive immune responses without significant increases in circulating proinflammatory cytokines, demonstrating its potential to deliver the therapeutic benefit that patients need while avoiding dose-limiting adverse events. The Primmune team is encouraged by our positive Phase 1 data and we look forward to the ongoing clinical development of PRTX007."
Presentation details:
Title: Activation of Innate and Adaptive Immune Response with a Clinical Stage TLR7 Agonist Prodrug PRTX007
Presenting Author: Curtis Scribner, M.D., Chief Medical Officer, Primmune
Abstract Number: CT180
Poster Board: 12
Session Title: First-in-Human Phase I Clinical Trials 2
Session Date and Time: Tuesday, April 18, 9:00 a.m. ET to 12:30 p.m. ET
Location: Orange County Convention Center, Poster Section 45
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.
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.
These data justify further exploration of PRTX007 as a potential cancer therapeutic. Primmune plans to conduct a future study evaluating PRTX007 in combination with a checkpoint inhibitor across the active doses identified in the Phase 1 study for the potential treatment of solid tumors.
About PRTX007
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. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-transformed pre-cancerous cervical lesions.