Vigil (gemogenovatucel-T)

Transfected plasmid components contain an expressive human GMCSF DNA segment to enhance anticancer immune functional response and a second component expressing bi-shRNAfurin which reduces TGFβ isomers (TGFβ1 and TGFβ2) thereby reducing cancer inhibition of the targeted immune response. Results generated to date justify advancement to confirmatory clinical trials supporting product regulatory approval.

Vigil is an autologous cellular immunotherapy which is designed to carry the full set of personal clonal neoantigens. Phase 2b results demonstrate a durable recurrence-free survival (RFS) and overall survival (OS) advantage for Vigil in a subset ovarian cancer population with an HRP cancer profile.

We have consolidated information regarding the role of the immune system in both disease progression and disease clearance with the aid of targeted therapies and immunotherapeutic agents. Additionally, we have characterized the treatment modalities currently indicated as the standard of care-such as bevacizumab and the immune CPIs-and those recently approved or in development, including Tivdak, Vigil, and chimeric antigen receptor (CAR) T-cells.

P2, N=92, Active, not recruiting, Gradalis, Inc. | Trial completion date: Jul 2023 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

NSA should be considered for application to investigational targeted therapies in order to identify populations most likely to benefit from treatment, in preparation for efficacy conclusive trials.

Results demonstrated safety of combination Vigil/TEM/IRI.

P2, N=25, Completed, Gradalis, Inc. | Active, not recruiting --> Completed | Trial completion date: Sep 2022 --> May 2022

Gemogenovatucel-T is a cellular immunotherapy manufactured from harvested tumor tissue transfected with a plasmid which encodes granulocyte macrophage colony stimulating factor (GM-CSF) and a short harpin RNA which specifically reduces the expression of furin and downstream targets TGF-β1, and TGF- β2...The entire process starting with blood DNA extraction and ending with report generation can be completed in about 3.5 days. The results show that a comprehensive oncology-focused sequencing panel can be an effective tool for focused gene-specific variant analysis.

At the same time, treatment with the Gemogenovatucel-T (Vigil) is safer than other treatment modalities and does not have any toxic effects. https://www.crd.york.ac.uk/prospero/, identifier (CRD42022300367).

ENTPD1 high may predict a more sensitive OC population to Vigil. Trial Registration NCT02346747

Using the NanoString Statistical Algorithm (NSA), we identify high expression of ENTPD1/CD39 (which functions as the rate-limiting step in the production of the immune suppressor adenosine from ATP to ADP) as a presumptive predictor of response to Vigil versus placebo regardless of HRP status on the basis of relapse free survival (median not achieved vs 8.1 months, p = 0.00007) and overall survival (median not achieved vs 41.4 months, p = 0.013) extension. NSA should be considered for application to investigational targeted therapies in order to identify populations most likely to benefit from treatment, in preparation for efficacy conclusive trials.

Further evidence of clinical benefit and safety has been demonstrated in combination with atezolizumab. Prolonged progression-free survival was improved in patients with PD-L1+ tumors (n = 8, hazard ratio = 0.304, 95% confidence interval, 0.0593-1.56, 1-sided P = .04715) compared with those with PD-L1- tumors. Vigil plus durvalumab was well tolerated and showed promising clinical activity in advanced BRCA-wt TNBC and stage III-IV recurrent/refractory OC patients.

P2, N=44, Active, not recruiting, Gradalis, Inc. | Trial completion date: Dec 2021 --> Jun 2023 | Trial primary completion date: Dec 2021 --> Jun 2023

In conclusion, results suggest durable activity of Vigil on RFS and OS and support further evaluation of Vigil in HRP ovarian cancer.

Results suggest a subset of ovarian cancer patients with enhanced susceptibility to Vigil immunotherapy. The hypothesis-generating data presented invites a validation study of Vigil in target identified populations, and supports clinical consideration of STRING-generated network application to biomarker characterization with other cancer patients targeted with Vigil.

Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed clinical benefit in both BRCA-wt and HRP molecular profile patients . Results suggest a unique molecular network that enhances sensitivity to Vigil therapy.

Vigil exhibited clinical benefit in HRP molecular profile patients.

P2, N=25, Active, not recruiting, Gradalis, Inc. | Trial completion date: Feb 2021 --> Sep 2022 | Trial primary completion date: Jan 2020 --> Jan 2021

Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted.

P2, N=44, Active, not recruiting, Gradalis, Inc. | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

Vigil immunotherapy as 1L maintenance in Stage III/IV ovarian cancer is well tolerated and showed significant RFS clinical benefit, particularly in BRCA1/2-wt disease.

The combination of Vigil immunotherapy and checkpoint inhibitor atezolizumab in recurrent OvC demonstrated safety and suggest a lower toxicity profile and a significant OS advantage in recurrent BRCA1/2-wt OvC patients treated with Vigil first followed by the combination of Vigil and Atezolizumab. Research Funding: None

Front-line use of vigil immunotherapy as maintenance in stage III–IV ovarian cancer is well tolerated and showed trend in RFS clinical benefit. Specifically, BRCA1 and BRCA2wt disease showed statistically significant benefit.

Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed RFS clinical benefit, particularly in BRCA1/2-wt disease. Research Funding: None

Front-line use of vigil immunotherapy as maintenance in stage III–IV ovarian cancer is well tolerated and showed trend in RFS clinical benefit. Specifically, BRCA1 and BRCA2wt disease showed statistically significant benefit.