Gradalis Announces Publication of Two Studies Demonstrating the Positive Results of Vigil® in Combination with Checkpoint Inhibitors

• In both studies, Gradalis’ lead program, Vigil,demonstrated a favorable safety profile when used in combination with checkpoint inhibitors, durvalumab or atezolizumab, without evidence of incremental toxicity relative to checkpoint inhibitors alone
• Administration of Vigil with durvalumab improved progression free survival in patients with PD-L1 positive tumors compared to those with PD-L1 negative tumors
• Administration of Vigil before atezolizumab showed increased overall survival and improved safety over atezolizumab before Vigil suggesting Vigil may heighten checkpoint inhibitor benefit

DALLAS, Oct. 03, 2022 (GLOBE NEWSWIRE) -- Gradalis, Inc., a privately held, late-stage clinical biotechnology company, today announced a peer-reviewed publication in Clinical Medicine Insights: Oncology demonstrating positive results from a pilot study investigating Vigil^® in combination with a PD-L1 checkpoint inhibitor, durvalumab (Imfinzi® - AstraZeneca), in patients with advanced triple negative breast cancer (TNBC) or recurrent/refractory ovarian cancer (OC). This study also suggests that administration of Vigil with durvalumab improved progression free survival (PFS) in patients with PD-L1 positive tumors compared to those with PD-L1 negative tumors.

Vigil is a novel, personalized cellular immunotherapy platform that is designed to decloak the full repertoire of a patient’s tumor neoantigens, reactivate the immune system, and summon key effector cells to deliver a durable clinical response. Vigil is the first cellular immunotherapy to demonstrate survival benefits in a randomized controlled trial of patients with solid tumors. The results of the Gradalis Phase 2b trial evaluating Vigil as frontline maintenance therapy in patients with ovarian cancer have been published in Lancet Oncology and presented at the American Society of Clinical Oncology. Vigil is also being studied in other cancer types.

“There is an unmet need for treatment of triple negative breast cancer and ovarian cancer tumors, which generally are poorly immunogenic and have shown limited response to checkpoint inhibitor therapy,” said Minal Barve, M.D., Chief Medical Officer for Mary Crowley Cancer Research, and principal investigator of the Vigil and durvalumab trial. “These initial results are exciting and suggest that Vigil in combination with durvalumab has the potential to enhance the patients’ immune response to their tumors relative to historical checkpoint inhibitor trials and speak to the promise of Vigil-based combination therapies.”

A second study published earlier this year in Cancer Gene Therapy, evaluated the impact of the administration of Vigil before and after atezolizumab (Tecentriq^® - Roche) to explore targeted effector cell expansion prior to checkpoint inhibition. This study demonstrated a trend toward increased overall survival (OS) and improved safety in the group that received atezolizumab first.

John Nemunaitis, M.D., Chief Scientific Officer of Gradalis commented, “These two clinical trials underscore the therapeutic utility of combining Vigil and checkpoint inhibitors without generating incremental toxicity relative to that shown with single agent checkpoint inhibitor therapy. The results of the atezolizumab study suggest that priming the immune system with Vigil prior to the administration of the checkpoint inhibitor may enhance overall efficacy and reduce adverse effects associated with checkpoint inhibitor therapy. This is very encouraging for the future development of Vigil for use in a sequential combination approach to synergistically enhance the benefit/risk profile for checkpoint inhibitor therapies.”

Vigil plus Durvalumab Combination Study

A single-arm pilot study investigating Vigil used in combination with durvalumab, a PD-L1 checkpoint inhibitor, evaluated the safety profile and preliminary efficacy of Vigil in 13 patients with advanced BRCA-wt triple negative breast cancer or recurrent/refractory ovarian cancer. The number of prior lines of chemotherapy in the intent to treat population was four and the median number of cycles of Vigil and durvalumab was six.

When used in combination with durvalumab, Vigil demonstrated a favorable safety profile. The results showed prolonged PFS in the intent to treat population, with a median PFS of 7.1 months and a median OS period that had not been reached after 14.7 months (the median follow-up period for all patients).

The durvalumab study also examined the impact of PD-L1 positivity on the patients' response. Generally, a PD-L1 positive patient is more likely to respond to a PD-L1 checkpoint inhibitor therapy. Median PFS had not been reached after 14.7 months in patients with PD-L1 positive tumors (n=8) compared to 1.61 months for PD-L1 negative patients (n=5), HR=0.304, 95% CI [0.0593-1.56], one-sided p=0.04715).

Vigil in combination with durvalumab demonstrated no grade 3 or greater adverse events that were attributed to Vigil by the investigators. Three study patients (23%) had a single grade 3 adverse event, all of which were attributed to durvalumab. These data demonstrate a safety profile that is at least comparable to the PACIFIC registrational trial of durvalumab monotherapy in non-small cell lung cancer that led to the approval of durvalumab. In that trial, 29.9% of patients had grade 3 or 4 toxic events.

These results were published in Clinical Medicine Insights: Oncology in an article entitled, “Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women with Relapsed BRCA-wt Triple Negative Breast or Ovarian Cancer.” The full text of the article can be found here: https://journals.sagepub.com/doi/10.1177/11795549221110501

Vigil plus Atezolizumab Combination Study

A two-arm pilot study of Vigil in combination with the checkpoint inhibitor, atezolizumab, demonstrated a trend towards increased overall survival and improved safety in the group that received atezolizumab first. This study was designed to evaluate the impact of the administration of Vigil before and after atezolizumab to explore targeted effector cell expansion prior to checkpoint inhibition. Checkpoint inhibitors are associated with a more generalized immune response, which can affect both healthy and tumor cells. Vigil is designed to focus immune response on only tumor cells and would be expected to reduce “off-target” effects on healthy cells associated with checkpoint inhibitor therapy.

In the 11 ovarian cancer patients receiving Vigil before atezolizumab, median OS had not been reached after 21.3 months (the median follow-up period for all patients) compared to 10.8 months in patients receiving atezolizumab before Vigil (n=10).

Regarding safety, atezolizumab attributed adverse events were observed in 61.3% of the Vigil first group compared to 96.7% of the atezolizumab first group. Grade 3 or higher treatment-related adverse events attributable to atezolizumab also tended to be observed at a lower rate in the Vigil first patient group (5.1%) compared to the atezolizumab first patient group (17.2%). This evidence supports 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.

The results of the Vigil and atezolizumab combination study were published in Cancer Gene Therapy in an article entitled, “Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer.” The full text of the article can be found here: https://www.nature.com/articles/s41417-021-00317-5

About Gradalis, Inc.

Founded in 2003, Gradalis is a privately held, late-stage clinical biotechnology company developing a personalized immunotherapy called Vigil, that has been tested in multiple studies in ovarian and other cancer tumor types. Based on its Phase 2b clinical trial results, the company is preparing to initiate a Phase 3 trial designed for product registration of Vigil in patients with ovarian cancer. 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 trial evaluating Vigil as frontline maintenance therapy in patients with ovarian cancer have been published in Lancet Oncology and presented at the American Society of Clinical Oncology. Vigil is being studied in other cancer types and 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 neoantigens, reactivate the immune system, and summon key effector cells to deliver a durable clinical response. When combined, these are a powerful Trifecta of anti-cancer activities, potentially eliminating even the elusive metastatic cells, and as shown in Phase 2 clinical studies in ovarian cancer, a potential gamechanger in oncology. Clinical trials of Vigil 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.

About Vigil

Vigil® is a novel, personalized immunotherapy platform designed to achieve a Trifecta of immune anticancer activity using a unique bi-shRNA DNA based plasmid and the patient’s own tumor tissue. The Trifecta of systemic activity involves knock down of TGFβ1 and TGFβ2 which function as tumor suppressor cytokines, increased GM-CSF expression to enhance local immune function and presentation of the patient’s clonal neoantigen epitopes via use of autologous cancer tissue. 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 (NCT02346747), Vigil showed a positive trend in the primary endpoint of recurrence free survival (RFS) in the overall population and a statistically significant improvement in RFS and overall survival (OS), with a median time of three years to date, in a pre-planned subgroup analysis of Stage III/IV newly diagnosed ovarian cancer patients with the BRCAwt molecular profile. In patients with tumors of the HRP type, significant additional improvement was seen in RFS and OS.

Additionally, Phase 1 results in a “basket” clinical trial have shown positive signals of activity in 19 tumor types and some patients treated with Vigil remain in the trial 48 months later. The company is preparing to initiate a clinical trial intended for product registration in patients with the HRP subtype ovarian cancer.

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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