IMNN-001

Overview

IMNN-001 (formerly GEN-1) is an investigational, intraperitoneal DNA‑mediated interleukin‑12 (IL‑12) gene therapy being developed for newly diagnosed advanced epithelial ovarian cancer, given with standard neoadjuvant/adjuvant carboplatin–paclitaxel. A randomized Phase I/II study (OVATION‑2; n=112) reported numerically improved progression-free and overall survival versus chemotherapy alone; results were published in Gynecologic Oncology in June 2025 and presented at ASCO 2025. A pivotal Phase 3 study (OVATION‑3) has begun enrollment. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

IMNN‑001 consists of a plasmid encoding human IL‑12 formulated in a synthetic lipopolymer (TheraPlas) and delivered intraperitoneally to drive local IL‑12 expression in the peritoneal tumor microenvironment. The goal is to remodel an immunosuppressive milieu by inducing downstream cytokines (e.g., interferon‑γ, TNF‑α) and enhancing antitumor immune activity while minimizing systemic IL‑12 toxicity observed with recombinant cytokine administration. Translational readouts from OVATION‑2 showed marked, localized increases of IL‑12 (~27‑fold), IFN‑γ (~62‑fold), and TNF‑α (~36‑fold) in peritoneal fluid after treatment. (aacrjournals.org)

Efficacy

• Randomized Phase I/II (OVATION‑2; n=112):
• Median PFS: 14.9 months with IMNN‑001 + chemo vs 11.9 months with chemo alone; HR 0.79 (95% CI 0.51–1.23). (pubmed.ncbi.nlm.nih.gov)
• Median OS: 46.0 vs 33.0 months; HR 0.69 (95% CI 0.40–1.19). R0 (no residual) resection rate at interval debulking: 64.6% vs 52.1%. Study was not powered for statistical significance. (pubmed.ncbi.nlm.nih.gov)

• In patients receiving PARP‑inhibitor maintenance, median PFS was 33.8 vs 22.1 months (HR 0.80), and OS was not estimable vs 37.1 months (HR 0.38), favoring IMNN‑001. (pubmed.ncbi.nlm.nih.gov)

• Phase Ib dose‑escalation (OVATION‑1; n=18):

• Among 14 evaluable patients pre‑surgery, radiologic responses were 86% (2 complete, 10 partial); 9/14 achieved R0 resection; median time to treatment failure was 18.4 months (ITT). (pubmed.ncbi.nlm.nih.gov)

Safety

• OVATION‑2: The regimen was generally well tolerated. The most common treatment‑emergent adverse events were gastrointestinal symptoms and cytopenias; no cytokine release syndrome or increased risk of serious immune‑related events was observed. (pubmed.ncbi.nlm.nih.gov)
• OVATION‑1: No dose‑limiting toxicities were reported across four dose levels (36–79 mg/m²). Grade 4 neutropenia occurred in eight patients and was attributed to chemotherapy; common related AEs included nausea, fatigue, abdominal pain/cramping, anorexia, diarrhea, and vomiting. (pubmed.ncbi.nlm.nih.gov)

Development status and dosing

IMNN‑001 has been evaluated as weekly intraperitoneal doses (Phase 2 used 100 mg/m²) given for up to 17 weeks across neoadjuvant and adjuvant periods alongside carboplatin–paclitaxel. A pivotal Phase 3 trial (OVATION‑3) in newly diagnosed advanced ovarian cancer is underway, with the first patient dosed on July 30, 2025. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Gynecologic Oncology (2025): OVATION‑2 randomized Phase I/II results and safety. (pubmed.ncbi.nlm.nih.gov)
• Clinical Cancer Research (2021): OVATION‑1 Phase Ib dose‑escalation study with clinical and immunologic data. (pubmed.ncbi.nlm.nih.gov)
• Review of GEN‑1/IMNN‑001 platform and intraperitoneal IL‑12 rationale. (pubmed.ncbi.nlm.nih.gov)
• Company communications on OVATION‑2 translational biomarkers and Phase 3 initiation (context on dosing and trial status). (investors.imunon.com)

Notes: OVATION‑2 was not powered for statistical significance; observed survival and surgical outcomes were numerically favorable and hypothesis‑generating pending confirmation in Phase 3. (pubmed.ncbi.nlm.nih.gov)

Last updated: Oct 2025