- Results demonstrate a significant survival benefit in the cTMB-H / HRP subset: median OS of almost 6 years (68 months) with Vigil vs. less than 2 years (19 months) for placebo (HR=0.23; p=0.008)
- 7-year OS rate of 45% with Vigil compared to 8% with placebo in cTMB-H / HRP subset
- Mechanistic mutation signatures (cTMB-H / HRP) linked to OS advantage from the Vigil Vital trial provide a foundation for future success
- Very favorable safety profile across all 91 patients enrolled with no Grade 3 or greater treatment-related toxicities and a median follow-up of 8.4 years
- FDA RMAT designation supports expedited development toward Phase 3 confirmatory trial for patients with cTMB-H / HRP ovarian cancer
DALLAS, Jan. 14, 2026 (GLOBE NEWSWIRE) -- Gradalis, Inc., a clinical-stage biotechnology company developing personalized anti-cancer therapies, announced compelling results from the Phase 2b VITAL trial evaluating Vigil (Gemogenovatucel-T), an autologous tumor-cell immunotherapy, as maintenance therapy in newly diagnosed Stage IIIb–IV epithelial ovarian cancer patients. The updated analysis, published in the JCO – Precision Oncology, highlights a clinically meaningful and statistically significant overall survival (OS) benefit in patients with clonal tumor mutational burden-high (cTMB-H) and homologous recombination proficient (HRP) molecular profile. The full text of the article can be found here.
John Nemunaitis, MD, Gradalis’ Chief Scientific Officer and co-founder stated: “Frontline ovarian cancer treatment protocols involving bevacizumab, PARP inhibitors and PD-1/PD-L1 inhibitors have failed to improve overall survival in patients with HRP tumors. To determine mechanistic mutation signatures associated with OS advantage, we conducted blinded post-hoc analyses of the 91 patients treated in the VITAL trial. Based on these data, we hypothesized that patients with an HRP profile and high clonal tumor mutation burden might achieve greater response when undergoing maintenance therapy with Vigil. Results published today validate our hypothesis demonstrating that Vigil delivered a median OS of nearly six years compared to less than two years with placebo. With FDA RMAT Fast Track designation, we are positioned to accelerate development and bring this innovative therapy to patients sooner.”
Overview of data:
- Patient population: The randomized, double-blind, placebo-controlled Phase 2b VITAL trial (NCT02346747) enrolled 91 patients with newly diagnosed Stage IIIb–IV epithelial ovarian cancer who achieved a clinical complete response following debulking surgery and frontline platinum-based chemotherapy (carboplatin/paclitaxel). Patients were randomized to receive gemogenovatucel-T (Vigil) (n=47) or placebo (n=44) as maintenance therapy. Across all 91 patients enrolled, the majority (>90%) had high-grade serous ovarian cancer and received standard frontline platinum-based chemotherapy before entering the study.
- Efficacy: Vigil demonstrated a substantial survival advantage in the cTMB-H / HRP patient subset (Vigil: 11; Placebo: 12), with a median overall survival of 68 months versus 19 months for placebo (HR=0.23; p=0.008) and a 7-year OS rate of 45% compared to 8%. Recurrence-free survival also favored Vigil (10 vs. 6 months; HR=0.41), and benefit was confirmed by Restricted Mean Survival Time (RMST) analysis. Exploratory biomarker analyses reinforced the specificity of benefit to HRP tumors with high clonal mutational burden.
- Safety: Safety analyses were conducted on the entire randomized population of 91 patients, ensuring a comprehensive assessment of tolerability beyond the molecularly defined efficacy subsets. Treatment was well-tolerated, with no Grade 3 or greater related adverse events and no long-term safety signals such as MDS or AML over 8.4 years of follow-up. The most common events were mild injection-site reactions, and no discontinuations were attributed to toxicity.
- Translational Findings: Molecular profiling confirmed that the vaccine preserved the patient’s clonal mutational and neoantigen profile (R²=0.98). Higher clonal neoantigen load and lower intratumor heterogeneity correlated with improved outcomes, supporting the mechanistic rationale for targeting clonal signals to drive durable immune responses.
- Blinded post-hoc bioinformatic analyses: To determine mechanistic mutation signatures associated with OS advantage, a whole exome sequencing bioinformatic pipeline assay was used to analyze all 91 patients. Data indicated that patients with clonal tumor mutational burden-high (cTMB-H) and homologous recombination proficient (HRP) disease might achieve greater response when undergoing maintenance therapy with Vigil.
About Vigil (gemogenovatucel-T)
Vigil® is a novel, triple function immunotherapy platform that modifies a patient’s tumor by using bi-shRNA to reduce furin, an enzyme which facilitates immunosuppressive TGF beta protein production, and to maximize DNA expression of GM-CSF, which stimulates the immune system and attracts key immune system effector cells, including T-cells. By utilizing the patient's own tumor as the antigen source, Vigil is designed to elicit an immune response that is specifically targeted and broadly relevant to each patient's unique clonal tumor neoantigens. In patients with HRP ovarian cancer and high clonal tumor mutational burden, where there is a high unmet medical need, Vigil has been granted a Regenerative Medicine Advanced Therapy designation by the FDA on the basis of a statistically significant and clinically meaningful improvement in OS.
Additionally, Phase 1 results in an “all-comer” clinical trial showed positive signals of activity in several different tumor types. Vigil has also demonstrated safety and benefit in two separate pilot studies when administered concurrently or in sequence prior to treatment with check point inhibitor therapy. The sequential treatment results support the hypothesis that Vigil administration prior to starting checkpoint inhibitor therapy may focus the immune effector population to the cancer, potentially enhancing activity and limiting off target side effects.
Vigil is the first cellular immunotherapy to demonstrate longer-term survival benefits in a randomized controlled trial of patients with solid tumors. The results of the company’s Phase 2b study have been published in Lancet Oncology, Gynecologic Oncology and presented at the American Society of Clinical Oncology.
About bi-shRNAi
Gradalis’ patented bi-functional short hairpin RNA interference (bi-shRNAi) technology platform is a DNA vector-based technology that produces both siRNA-like and miRNA-like molecules in cells for degrading certain mRNA targets. By utilizing both the siRNA and miRNA modes of action, the bi-shRNAi technology enables and enhances RNAi drug action in a broad spectrum of diverse cell populations resulting in wide bioavailability and pharmacodynamics and pharmacokinetics. As a DNA vector-based technology, bi-shRNAi technology can be constructed within a single plasmid to impact multiple targets thereby further broadening the range of drug action.
About Gradalis, Inc.
Gradalis is a clinical-stage biotechnology company advancing Vigil®, a Phase 3–ready, personalized immunotherapy built on its proprietary bi-shRNA platform. Vigil harnesses the patient’s own tumor clonal neoantigens - without requiring new targets for each indication - to activate the immune system and deliver durable antitumor responses. In the Phase 2 VITAL trial, Vigil demonstrated a statistically significant and clinically meaningful overall survival benefit in ovarian cancer patients who are homologous recombination proficient (HRP, which includes BRCA wild type) and have high clonal tumor mutation burden (cTMB-H). The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to Vigil on the basis of these results. HRP status occurs in many solid tumor indications, and combined with cTMB, enables Gradalis to identify the right patients for its therapy. Early clinical experience has shown signs of efficacy across several different solid tumors of high unmet need, underscoring Vigil’s potential for broad use and long-term value creation. Learn more at www.gradalisinc.com.
Forward-Looking Statements
This press release contains forward-looking statements, including, without limitation, statements regarding the success, cost, and timing of our product development activities and clinical trials, our plans to research, develop, and commercialize our product candidates, and our plans to submit regulatory filings and obtain regulatory approval of our product candidates. These forward-looking statements are based on Gradalis’ current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include but are not limited to: (a) the timing, costs, and outcomes of our clinical trials and preclinical studies, (b) the timing and likelihood of regulatory filings and approvals for our product candidates, and (c) the potential market size for our product candidates. These forward-looking statements speak only as of the date made and, other than as required by law, we undertake no obligation to publicly update or revise any forward-looking statements. This press release does not constitute an offer to sell, or a solicitation of an offer to buy, any securities.
Gradalis Contact
Mark Early
(214) 442-8161
mearly@gradalisinc.com
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