Gradalis Highlights Importance of Clonal Neoantigen Targeting for Clinical Benefit of Vigil® in Oncology Reviews Publication

• Evidence from multiple researchers supports Vigil enhancement of clonal neoantigen effector cell response and correlation to relapse free survival and overall survival benefit
• Targeting clonal neoantigens to generate an effector cell response is more effective than targeting subclonal neoantigens
• HRP profile is associated with higher clonal neoantigen profiles compared to HRD/BRCA mutant
• Results of Vigil Phase 2b study in HRP ovarian cancer patients are consistent with these findings

DALLAS, Sept. 28, 2023 (GLOBE NEWSWIRE) — Gradalis, Inc. announced the peer-reviewed publication in Oncology Reviews, a Frontiers Open Access Journal, highlighting Vigil activity in ovarian cancer related to clonal neoantigen expression and the HRP molecular profile. Vigil is a personalized immunotherapy that has been tested in multiple studies in ovarian and other cancer tumor types. The publication entitled, “Rationale of Homologous Recombination Proficient Molecular Profile as Biomarker for Therapeutic Targeting in Ovarian Cancer,” provides further insight into why HRP positive ovarian cancer patients are more likely to respond to Vigil immunotherapy. The full text of the article can be found here.

“There is a rising tide of key research demonstrating the importance of targeting clonal neoantigens in preclinical and clinical studies by multiple investigators and Gradalis,” said John Nemunaitis, MD, CSO of Gradalis, and corresponding author on the paper. “There is a clear opportunity for Vigil to differentiate and address the unmet medical need in HRP ovarian cancer patients. Vigil is designed to improve the immune system’s ability to produce effector cells that travel and bind to clonal neoantigen targets. This activity induces a targeted lethal immune response against cancer. Growing research shows that using clonal neoantigens as a target for tumor cell disruption is critical to effective therapy. Clonal neoantigens can be different for each patient, so a “one size fits all” allogeneic approach may not provide long lasting efficacy in a majority of patients.”

Data supporting efficacy of Vigil in the ovarian cancer population includes Phase 1, 2a and 2b trial results. In the Phase 2b trial, the greatest benefit following Vigil treatment was observed in patients with the highest capacity for DNA repair—those with the HRP molecular profile in both relapsed free survival and overall survival. This effect was durable and continued with long-term follow-up for three years. Results suggest that Vigil treatment in HRP positive ovarian cancer patients enhance immunotherapeutic proficiency that is mediated by the capacity for high clonal neoantigen targeting.

“With over 300,000 newly diagnosed women this year worldwide and over 200,000 expected deaths, ovarian cancer is an indication that is ripe for innovation,” says Rodney Rocconi, MD, Director of the University of Mississippi Medical Center Cancer Center and Research Institute and study investigator. “Further, although checkpoint inhibitors and other immunotherapy approaches are great advancements to the field, several large studies have failed to show meaningful clinical benefits in ovarian cancer. Therefore, the demonstration of relapse free and overall survival improvement with Vigil is a remarkable achievement that underscores Vigil’s unique mechanism of action and potential to address this growing unmet medical need for differentiated therapeutic options. This is particularly important in the HRP population where the durable effect with Vigil has been observed over multiple years of follow up.”

About Ovarian Cancer
Ovarian cancer patients are composed of two groups with differing levels of DNA repair capability, each representing about 50% of ovarian cancer patients: HRP – good DNA repair; HRD/BRCA-mutant – poor DNA repair. HRP tumors are better able to repair DNA and the clonal neoantigens are better preserved. Patients with the HRD/BRCA-mutant profile have an impaired DNA repair that is associated with higher subclonal neoantigen profiles compared to the HRP profile. As a result, HRP patients’ tumors should respond better to Vigil therapy than HRD/BRCA-mutant patients. Results of Vigil in a Phase 2b study in HRP ovarian cancer patients are consistent with these findings.

About Vigil
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. Vigil therapy has been well tolerated in Phase 1, 2a and 2b clinical studies.

In VITAL, a multicenter, randomized, double-blind, placebo-controlled Phase 2b trial in Stage III/IV newly diagnosed, frontline ovarian cancer patients, Vigil showed a positive trend in the primary endpoint of recurrence free survival (RFS) in the overall population and a statistically significant improvement in the secondary endpoint of recurrence free survival and overall survival (OS), with a median survival time of three years to date, in patients with the BRCAwt molecular profile. Importantly in patients with tumors of the HRP type, where there is a high unmet medical need, a statistically significant improvement was seen in RFS and OS.

Additionally, Phase 1 results in an “all-comer” clinical trial have shown positive signals of activity in 19 tumor types and some patients treated with Vigil remain in the study 48 months later. The company is preparing to initiate a Phase 2 clinical study in platinum sensitive recurrent ovarian cancer patients with the HRP molecular profile.

About Gradalis, Inc.
Founded in 2006, Gradalis is a privately held, clinical stage biotechnology company developing a personalized immunotherapy called Vigil, that has been tested in multiple studies in ovarian and other cancer tumor types. Vigil is the first cellular immunotherapy to demonstrate 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 and presented at the American Society of Clinical Oncology. Vigil has shown positive results in combination with checkpoint inhibitors.

Gradalis’ Vigil platform uses the patient’s immune system to target the entire tumor. Based on multiple clinical studies, Gradalis has developed an oncology platform that is designed to decloak the full repertoire of a patient’s tumor antigens, including all clonal neoantigens, reactivate the immune system, and summon key effector cells to deliver a durable clinical response. When combined, these are a powerful Trifecta of anticancer activities, potentially eliminating even the elusive metastatic cells, and as shown in Phase 2 clinical studies in ovarian cancer, a potential gamechanger in oncology. Our clinical trials have also demonstrated that Gradalis’ platform is better tolerated compared to standard cancer treatments since Vigil uses the patient’s immune system operating within its natural state of balance rather than in an artificial overdrive as with some technologies. Vigil utilizes proprietary bi-shRNA technology that has been proven to silence multiple genes in a variety of cancers and has the potential to be used in other diseases.

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

LifeSci Advisors Contact
Joyce Allaire
+1 (617) 435-6602
jallaire@lifesciadvisors.com