Gradalis Awarded $9.9 Million Grant From the Cancer Prevention and Research Institute of Texas

DALLAS, Nov. 16, 2023 (GLOBE NEWSWIRE) -- Gradalis, Inc., a leader in the development of personalized anti-cancer cellular therapies for patients with solid tumors, announced today that it has been awarded a $9.9 million Product Development Research grant from the Cancer Prevention and Research Institute of Texas (CPRIT). The funds will be used to support the company's Phase 2 clinical study of Vigil® in platinum-sensitive patients who have recurrent ovarian cancer with a homologous recombination proficient (HRP) molecular profile. These patients face an acutely high unmet medical need due to the removal of PARP inhibitor therapies in 2022. The study is designed as a pivotal trial to confirm the positive survival results seen in ovarian cancer patients with the HRP profile tumors in Gradalis’ earlier VITAL study in frontline maintenance therapy. The company intends to pursue accelerated approval based on positive results.

The company’s pioneering immuno-oncology therapy, Vigil, decloaks the full repertoire of tumor antigens, including the patient’s clonal neoantigens, reactivates the immune system, and summons key effector cells to deliver a durable clinical response. Vigil’s approach enables the very powerful immune system, which has been honed over eons to specifically identify the optimal targets on tumor cells required to destroy the tumor cells.

The result is a dramatic expansion of the effector cell population targeting clonal neoantigens throughout the body and destroying metastasized tumor cells. The company has shown in multiple studies that Vigil therapy causes the immune system to generate a reliable increase in T-cells that specifically target the tumor cells. In Phase 1, 2A and 2B studies, Vigil has been shown to be well tolerated – no Grade 3 or 4 treatment related adverse events were seen and no dose modifications were required.

“We are honored to have been approved by CPRIT for this award which provides additional capital to support the clinical development of Vigil and external validation of our technology by the world class experts who conducted medical, scientific and commercial diligence on behalf of CPRIT,” said Steve Engle, CEO of Gradalis.

Clonal neoantigens are tumor initiating mutations, and research by others has shown that the targeting of clonal neoantigens predicts survival in cancer patients. This targeting is critical to achieving durable efficacy. By utilizing the patient’s own tumor as the source for immunologic targets, Vigil is designed to elicit an immune response that is specifically targeted and broadly relevant to each patient's unique “clonal” tumor neoantigens. Other engineered therapeutic approaches including CAR-T, TILs and some cancer vaccines may be limited by an inability to identify or target the key clonal neoantigens.

“This award will accelerate the start-up of our Phase 2 study in recurrent ovarian cancer patients who face a very difficult path due to the limited effectiveness of chemotherapy and the recent withdrawals of PARP inhibitors. We expect the study will confirm Vigil’s ability to target each patient’s unique clonal neoantigens, the elimination of which has been shown by other research to be critical in achieving a durable overall survival benefit,” commented John Nemunaitis, MD, Gradalis’ Chief Scientific Officer and co-founder.

“Following the extensive review of several drug development opportunities, CPRIT was impressed with Gradalis' Vigil product activity and clinical benefit results. We look forward to continued relationship with Gradalis as results of the Phase 2 trial unfold,” said Ken Smith, Ph.D., Chief Product Development Officer at CPRIT.

About the Cancer Prevention and Research Institute of Texas
Since its founding in 2007, CPRIT has awarded more than $3 billion in grants to Texas research institutions and organizations through its academic research, prevention, and product development research programs. CPRIT has also recruited 293 distinguished researchers to Texas, supported the establishment, expansion, or relocation of 56 companies to Texas, and supported nearly 9 million prevention services reaching all 254 counties in Texas. In 2019, Texas voters approved a constitutional amendment to provide an additional $3 billion to CPRIT for a total $6 billion investment in cancer research and prevention.

About Ovarian Cancer
In the US, over 20,000 patients are diagnosed with ovarian cancer each year. The majority of women (65%) diagnosed with ovarian cancer present in an advanced stage (Stage III/IV). Even with current therapies, 65% will recur within two years and 14,000 patients will succumb to the disease each year. Over 230,000 patients are living with ovarian cancer in the U.S.

Ovarian cancer patients are composed of two groups with differing levels of DNA repair capability, each representing about 50% of ovarian cancer patients: the HRP group has good DNA repair capability and the HRD/BRCA-mutant group has poor DNA repair capability. Virtually all ovarian cancer patients are tested for HRP/HRD and reimbursement is covered by payors.

Because HRP tumors are better able to repair DNA, the clonal neoantigens are better preserved. Patients with the HRD/BRCA-mutant profile have an impaired DNA repair mechanism that is associated with a smaller proportion of clonal neoantigens compared to the patients with the HRP profile. As a result, HRP patients’ tumors would be expected to 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. The company is preparing to initiate a Phase 2 clinical study in platinum-sensitive recurrent ovarian cancer patients with the HRP profile.

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 RFS and overall survival (OS), with a median survival time of three years to date, in patients with the BRCAwt molecular profile. Most importantly in patients with tumors of the HRP molecular profile 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 different tumor types and some patients treated with Vigil remain in the study 48 months later. Vigil has also demonstrated safety and benefit in two separate 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.

The Vigil manufacturing process takes two days. It does not require the bioreactors and other time consuming and costly processes required by other cell therapies. Following the initial removal of the tumor, a small amount of tumor tissue is shipped to the company’s manufacturing plant in Dallas, Texas where its genetics are modified to produce the immune system enhancing effects. It is then put in vials and stored for in-office intradermal administration by the patient’s physician every three to four weeks for an average four to six month course of treatment.

About Gradalis, Inc.
Founded in 2006, Gradalis is a privately held, clinical stage biotechnology company developing a new category of 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 longer-term overall 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 a pioneering 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

LifeSci Advisors Contact
Joyce Allaire
+1 (617) 435-6602

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