Vigil (gemogenovatucel-T) / Gradalis - LARVOL DELTA

VITAL: A Trial of Vigil for Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=92 | Active, not recruiting | Sponsor: Gradalis, Inc. | Trial completion date: Dec 2025 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation. (PubMed, Hereditas) - "These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • TGFB1 • TGFB2 • TLN1

FANG Ovarian: A Trial of FANG™ Vaccine for Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=39 | Completed | Sponsor: Gradalis, Inc. | N=145 ➔ 39

Enrollment change • Oncology • Ovarian Cancer • Solid Tumor

Exome sequencing shows same pattern of clonal tumor mutational burden, intratumor heterogenicity and clonal neoantigen between autologous tumor and Vigil product. (PubMed, Sci Rep) - "Correlation between tumor and Vigil for the cNEO and ITH metrics, showed R2 values of 0.95 and 0.87, respectively. The consistency of the Clonal Neoantigen pipeline results with previously published data as well as the agreement between results for tumor and Vigil for the entire system provide a strong basis of support for utilization of this pipeline for prospective determination of cTMB, cNEO, and ITH values in clinical tumor tissue in order to explore possible correlative relationships with clinical response parameters."

IO biomarker • Journal • Tumor mutational burden • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • TMB

Gradalis Announces Development of Clinically Relevant Exome Sequencing Bioinformatics Pipeline to Determine Clonal Tumor Mutation Burden (GlobeNewswire) - "Gradalis, Inc...announced a peer-reviewed publication in Scientific Reports. The paper details the methods and validation of Gradalis’ exome sequencing procedure and associated bioinformatics pipeline for identifying signal patterns that drive cancer growth and spread....The study highlights a novel approach to identify clonal mutation signals which provide the greatest potential to result in clinical benefit to immunotherapy as well as the optimal cancers amenable to this therapeutic approach. Furthermore, the research offers a deeper mechanistic insight into the effects observed with Gradalis’ Vigil, an investigational immunotherapy platform being developed for various cancers."

Clinical • Oncology

Gradalis Secures FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for Vigil (Gemogenovatucel-T): An Investigational Personalized Immunotherapy for Advanced Ovarian Cancer (GlobeNewswire) - "Gradalis, Inc., a clinical-stage biotechnology company developing personalized anti-cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted Gradalis’ personalized investigational cellular immunotherapy, Vigil (Gemogenovatucel-T) Regenerative Medicine Advanced Therapy (RMAT) designation based on favorable clinical results from the ongoing Phase 2b VITAL trial."

FDA event • Ovarian Cancer

Repair Assisted Damage Detection (RADD) as a predictive biomarker for immunotherapy response in ovarian cancer. (PubMed, Gynecol Oncol) - P2 | "RADD revealed DNA repair proficiency without mutation signatures or expression profiling. High DNA damage levels show improved survival for Vigil maintenance therapies and are correlated with immune evasion proteins. The persistence of DNA lesions in the genomic DNA offers a new biomarker for immunotherapy patient stratification."

Biomarker • IO biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • ENTPD1

Gemogenovatucel-T (Vigil): bi-shRNA plasmid-based targeted immunotherapy. (PubMed, Future Oncol) - "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."

Journal • Review • Oncology • FURIN • TGFB1 • TGFB2

3D engineered scaffold for large-scale Vigil immunotherapy production. (PubMed, Sci Rep) - "Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor

Clonal Neoantigen: Emerging "Mechanism-based" Biomarker of Immunotherapy Response. (PubMed, Cancers (Basel)) - "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."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Tumor-specific neoantigens • Oncology • Ovarian Cancer • Solid Tumor • TMB

Gradalis Awarded $9.9 Million Grant From the Cancer Prevention and Research Institute of Texas (GlobeNewswire) - "Gradalis...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."

Financing • Ovarian Cancer

Gradalis to Host Virtual KOL Discussion on the Vigil Platform Entering Phase 2 for Platinum-Sensitive Recurrent Ovarian Cancer on October 25, 2023 (GlobeNewswire) - "Gradalis, Inc. announced that it will host a virtual KOL discussion on the Vigil^® platform entering Phase 2 for platinum-sensitive recurrent ovarian cancer on Wednesday, October 25, 2023 at 11:00am ET....The event will feature Rodney P. Rocconi, M.D., Director, Cancer Center & Research Institute and Professor, Gynecologic Oncology at the University of Mississippi Medical Center, who will discuss the unmet medical need and current treatment landscape for patients suffering from ovarian cancer, along with the potential for Vigil, a fully personalized, patient-specific cancer immunotherapy with applications across multiple solid tumor types including ovarian cancer."

P2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Advances in Targeted Therapy for the Treatment of Cervical Cancer. (PubMed, J Clin Med) - "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."

Journal • Review • Cervical Cancer • Oncology • Solid Tumor

Gradalis Highlights Importance of Clonal Neoantigen Targeting for Clinical Benefit of Vigil in Oncology Reviews Publication (GlobeNewswire) - "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...'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..."

Media quote • Gynecologic Cancers • Oncology • Ovarian Cancer

Gradalis Highlights Importance of Clonal Neoantigen Targeting for Clinical Benefit of Vigil in Oncology Reviews Publication (GlobeNewswire) - "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....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."

Review • Gynecologic Cancers • Oncology • Ovarian Cancer

VITAL: A Trial of Vigil for Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=92 | Active, not recruiting | Sponsor: Gradalis, Inc. | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Surgery • Trial completion date • Trial primary completion date • Tumor cell • Oncology • Ovarian Cancer • Solid Tumor

VITAL: A Trial of Vigil for Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=92 | Active, not recruiting | Sponsor: Gradalis, Inc. | Trial completion date: Jul 2023 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

ENTPD1/CD39 as a predictive marker of treatment response to gemogenovatucel-T as maintenance therapy in newly diagnosed ovarian cancer. (PubMed, Commun Med (Lond)) - P2 | "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."

Biomarker • IO biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • CSF2 • ENTPD1 • TGFB1 • TGFB2

A Trial of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Gradalis, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ May 2022

Biomarker • Metastases • Trial completion • Trial completion date • Cervical Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer • PD-L1

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide (clinicaltrials.gov) - P3 | N=32 | Terminated | Sponsor: Gradalis, Inc. | N=114 ➔ 32 | Active, not recruiting ➔ Terminated; Slow accrual and as a result, a strategic business decision was made to terminate enrollment.

Combination therapy • Enrollment change • Trial termination • Tumor cell • Ewing Sarcoma • Oncology • Rare Diseases • Sarcoma • Solid Tumor

Evaluation of a 293 gene oncology-focused exome sequencing panel for screening of ovarian cancer patients for BRCA mutations as a prerequisite for autologous cellular immunotherapy manufacturing (AACR 2023) - "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."

Clinical • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • CSF2 • FURIN • TGFB1

Here to Stay: Progress Solidifies the Future of Cell Therapy (CGTLive) - "'What is interesting about SS is that if you can find a patient that's HLA-A*02, they have about 60% to 80% chance of expressing the target. This happens across all solid tumors, but not at this rate. It may be 1%, it may be 2%, but we need to identify these patients. There are a lot of screening efforts going on, because not only is this a wonderful therapy with durability, [but] some patients are now doing well after a single treatment at 3 years. Afami-cel is going to go across solid tumors once we can find and identify those patients,' SPEARHEAD-1 study investigator Brian Van Tine, MD...told CGTLive....Sarcoma trials are so hard to do, because it's such a rare disease. And so just the fact that they've been able to even get this done is just a huge accomplishment,” Betof Warner said, referring to the SPEARHEAD-1 trial."

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A Trial of FANG™ Vaccine for Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=145 | Completed | Sponsor: Gradalis, Inc. | Active, not recruiting ➔ Completed | N=44 ➔ 145

Enrollment change • Trial completion • Tumor cell • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor

Gradalis Announces Publication in Clinical Cancer Research Featuring Positive Results from a Study Evaluating Vigil in Combination Therapy for Patients with Recurrent Ewing's Sarcoma (GlobeNewswire) - P3 | N=114 | VITA (NCT03495921) | Sponsor: Gradalis, Inc. | "Gradalis, Inc...announced that data from a pilot study evaluating Vigil in combination therapy for the management of recurrent Ewing’s Sarcoma was published online in Clinical Cancer Research....Efficacy: Observed two partial response (PR) patients by RECIST, both showed histological complete response (CR) without additional cancer therapy at long term follow up. Median PFS was 8.2 months (95% CI, 4.3-NA). Five of eight patients showed stable disease (SD) or better for ≥ 6 months. Patient specific EWS/FLI1 ctDNA was detectable in all eight evaluable patients at baseline."

P3 data • Ewing Sarcoma • Oncology • Sarcoma

ENTPD1 as predictive marker of treatment response to Gemogenovatucel-T (Vigil) in newly diagnosed ovarian cancer (SITC 2022) - P2 | "ENTPD1 high may predict a more sensitive OC population to Vigil. Trial Registration NCT02346747"

Biomarker • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • CSF2 • ENTPD1 • TGFB1 • TGFB2