Pexa-Vec (pexastimogene devacirepvec) / SillaJen, Lee's Pharm, GC Biopharma, Transgene - LARVOL DELTA

Liver Transplantation Following Hepatocellular Carcinoma Rupture and Long-Term Immunotherapy: A Case Report. (PubMed, J Gastrointest Cancer) - "ICIs alone or in combination with oncolytic immunotherapy may serve as novel downstaging strategies in advanced, ruptured HCC. Successful LT with long-term disease-free survival challenges traditional concerns about peritoneal seeding. Larger studies are required to define optimal patient selection, timing, and safety of pre-transplant ICIs. A 54-year-old man with advanced, ruptured liver cancer had an unexpectedly stable course over four years while receiving immunotherapy and an oncolytic virus. He later underwent a liver transplant and remains cancer-free two years later, illustrating the unpredictable nature of some severe liver cancer cases."

Journal • Fibrosis • Hepatocellular Cancer • Immunology • Liver Cancer • Oncology • Solid Tumor • Transplant Rejection • Transplantation

Killing to cure: harnessing poxvirus-driven cell death for viral immunotherapy. (PubMed, Immunol Lett) - "We discuss the development of Olvimulogene nanivacirepvec (Olvi-Vec), Pexastimogene devacirepvec (Pexa-Vec), and other candidates; the basic biology of poxviruses; their manipulation of host antiviral defences; and the pathways of regulated cell death they can induce, including apoptosis, necroptosis, pyroptosis, and ferroptosis. We examine the potential for optimising oncolysis through targeted genetic modification and combination therapy, with the aim of enhancing the immunogenicity of cell death to overcome the immunosuppressive tumour microenvironment and to enhance adaptive antitumour immune responses."

Journal • Review • Oncology

Oncolytic Viruses in Cancer Therapy: Mechanisms, Challenges, and Emerging Clinical Applications. (PubMed, Ann Pharm Fr) - "Several OVs, such as herpes simplex virus 1 (HSV-1), human adenovirus type 5 (HAdV-C5), mammalian orthoreovirus type 3 Dearing strain (T3D; pelareorep), and Vaccinia virus-derived platforms (e.g., JX-594/Pexa-Vec), have shown significant therapeutic efficacy. Among them, Talimogene laherparepvec (T-VEC) (a genetically engineered HSV-1) has been approved by the Food and Drug Administration for melanoma treatment...OVT offers a dual-action therapeutic approach and holds significant promise in the field of precision oncology. Continued innovation and clinical validation are essential for its widespread adoption in cancer care."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Jennerex Biotherapeutics | Phase classification: P1b ➔ P1

Phase classification • Colorectal Cancer • Oncology • Solid Tumor • RAS

A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib (clinicaltrials.gov) - P2 | N=129 | Completed | Sponsor: Jennerex Biotherapeutics | Phase classification: P2b ➔ P2

Phase classification • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

JX594-REN026: A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma (clinicaltrials.gov) - P1/2 | N=95 | Completed | Sponsor: SillaJen, Inc. | Active, not recruiting ➔ Completed | Phase classification: P1b/2a ➔ P1/2

Phase classification • Trial completion • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Oncolytic vaccinia virus JX-594 shows subtype-specific activity and candidate biomarkers in gastric cancer cell lines. (PubMed, Sci Rep) - "Notably, JX-594 activity was not correlated with TK1 or EGFR expression, suggesting additional determinants of viral susceptibility in GC. These findings provide preclinical evidence that molecular heterogeneity influences the response of GC to oncolytic virotherapy and support further investigation of JX-594 as a potential therapeutic strategy for gastric cancer."

Journal • Preclinical • Epstein-Barr Virus Infections • Gastric Cancer • Infectious Disease • Microsatellite Instability • Oncology • Solid Tumor • EGFR • IL1A • IL4I1 • MMRN2 • MSI • MX1

Oncolytic virus exhibits potent antitumor and immunomodulatory effects in triple-negative breast cancer using syngeneic and PDX models (AACR 2026) - "Although several studies have explored oncolytic virus–based therapies for TNBC, preclinical validation using PDX models remains extremely limited. Our findings provide robust in vivo evidence supporting the therapeutic potential of JX-594 and establish a translational foundation for advancingoncolytic virotherapy in TNBC."

Immunomodulating • IO biomarker • Oncolytic virus • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD20 • CD31 • CD4 • CD8 • CSF2 • PD-1 • PD-L1 • PECAM1

Vascularized gastric cancer 3D co-culture model using a microphysiological system as an oncolytic virus testing platform (AACR 2024) - "JX-594 had an inhibitory effect on tumor-induced angiogenesis in our vascularized gastric cancer in vitro 3D human cell co-culture model, demonstrating the utility of the platform as a tool to interrogate the effects of an oncolytic virus on both tumor cell killing and tumor-induced angiogenesis."

Oncolytic virus • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Antitumor activity of the oncolytic virus JX-594 in patient-derived xenograft models of triple-negative breast cancer (SABCS 2025) - "This study demonstrates that intratumoral administration of the oncolytic vaccinia virus JX-594 effectively suppresses tumor growth in PDX models of TNBC. JX-594 induces tumor cell death, inhibits proliferation, and disrupts tumor vasculature, collectively contributing to its potential antitumor activity. These findings support the potential of JX-594 as a promising therapeutic strategy for treatment of TNBC."

IO biomarker • Oncolytic virus • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD31 • ER • HER-2 • PECAM1 • PGR

The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management. (PubMed, Cancers (Basel)) - "Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance...Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP)...Advances in delivery, such as convection-enhanced infusion and blood-brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies."

Journal • Review • Brain Cancer • Glioblastoma • Glioma • Herpes Simplex • High Grade Glioma • Infectious Disease • Measles • Oncology • Solid Tumor

BAP1 as a predictive biomarker of therapeutic response to oncolytic vaccinia virus for metastatic renal cell carcinoma therapy. (PubMed, Cancer Immunol Immunother) - "We identified BAP1 as a potential predictive biomarker for JX-594 treatment and explored its underlying mechanisms. However, given that the study used immunodeficient models, the findings reflect tumor-intrinsic interferon responses and require further validation in immunocompetent models to assess immune microenvironment modulation and clinical relevance."

Biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BAP1 • IFNB1 • IRF7

Oncolytic virotherapy and tumor microenvironment modulation. (PubMed, Clin Exp Med) - "Among the most significant advancements, T-VEC, an FDA-approved herpesvirus, has been modified to express GM-CSF, enhancing immune activation in metastatic melanoma. Similarly, JX-594, a vaccinia virus, has been engineered for selective replication in tumor cells, demonstrating the potential of OVs to combine direct oncolysis with immune modulation. Other HSV-based OVs, such as HF10 and HSV1716, further highlight the ability of OVs to enhance immune cell infiltration and increase antigen presentation within the TME...Advances in viral engineering and immunomodulation hold the potential to revolutionize cancer treatment, offering more precise and effective therapeutic options. This review provides a comprehensive analysis of current progress in oncolytic virotherapy, emphasizing its potential to remodel the TME and improve clinical outcomes."

Biomarker • IO biomarker • Journal • Review • Immune Modulation • Immunology • Infectious Disease • Measles • Melanoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Systemically Administered Oncolytic Vaccinia Virus Enhances the In Vivo Antitumor Effects of RTKI and Anti-PD-1 Based Therapies in an Immunocompetent Renal Cancer Model (KCRS 2025) - "In vivo, while Cabozantinib, and treatment doublets had enhanced antitumor activity compared to single agents, the mJX-594, Cabozantinib and anti-PD-1 antibody combination was associated with more profound and prolonged antitumor activity and survival...The non-overlapping mechanisms of VV oncolysis, as well as cabozantinib enhancement of VV tumor penetration, leading to enhanced apoptosis may explain the effects of the virus-drug combination. The superiority of the triplet compared to doublets (C+VV or C+anti-PD-1) suggests that oncolytic viruses, in particular oncolytic VV can synergize with current anti-RCC therapies."

IO biomarker • Oncolytic virus • Preclinical • Genito-urinary Cancer • Infectious Disease • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CSF2

Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus. (PubMed, Molecules) - "Aptamers that specifically bind to the JX-594 strain of the vaccinia virus were developed earlier. The synergistic effect of the VV-GMCSF-Lact combination with the aptamers in the presence of serum was investigated using human glioblastoma cells. This proposed approach allowed us to conduct a preliminary screening of sequences using in silico modeling and experimental methods, and identified potential candidates that are capable of shielding VV-GMCSF-Lact from virus-neutralizing antibodies."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CSF2

Spatial Analysis of Tumor-Infiltrating Lymphocytes in mRCC Patients Treated with Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus plus GM-CSF) and cemiplimab (REGN2810; Anti-PD-1) (EORTC-NCI-AACR 2024) - "AI-powered spatial analysis suggests that combination therapy with Pexa-vec and cemiplimab enhances the immune response, evidenced by increased TIL densities in the tumor microenvironment.Table 1: Changes in TIL Densities from Pre- to Post-TreatmentMeasureCohortPre-Treatment (mm²)(Median, IQR)Post-Treatment (mm²)(Median, IQR)p-value isTILOverall (n = 18)87.53 (179.37-114.65)214.02 (257.50-389.74)0.0040 Arm A (n = 9)41.30 (257.13-81.61)190.17 (830.30-389.34)0.0078 Arm B (n = 9)165.43 (180.52-147.69)390.17 (340.11-387.14)0.1641iTILOverall (n = 18)88.89 (129.08-116.99)161.11 (376.62-321.79)0.0237 Arm A (n = 9)56.42 (125.56-101.70)157.44 (421.03-469.55)0.0273 Arm B (n = 9)96.27 (57.33-132.29)154.92 (194.87-184.03)0.3716sTILOverall (n = 18)100.91 (291.38-193.61)219.37 (370.85-466.27)0.0599 Arm A (n = 9)35.59 (257.13-67.38)140.55 (286.46-157.15)0.0391 Arm B (n = 9)303.37 (171.24-319.84)353.58 (189.15-735.39)0.4961"

Clinical • IO biomarker • Tumor-infiltrating lymphocyte • Oncology • Renal Cell Carcinoma • CSF2

‘Pexa-Vec’ SillaJen, return of bio representative player?... Successful bequest of 100 billion won [Google translation] (Investing.com) - "Shinlazen, which narrowly escaped the crisis after going to the brink of delisting, is showing signs of recovery. It has also succeeded in securing R&D funds by raising paid-in capital of 100 billion won....Sillazen plans to invest nearly 90 billion won of the funds secured this time into R&D for PEXA-VEC, BAL0891, SJ-600 series. The remaining funds are expected to flow into the U.S. subsidiary Sillazen Bio. The plan is to get back on track by focusing resources on anti-cancer R&D, including kidney cancer and solid cancer."

Financing • Kidney Cancer • Oncology • Solid Tumor

SillaJen meets with partner Regeneron at Bio USA [Google translation] (HIT News) - "SillaJen...announced on the 11th that it discussed various cooperation plans with global pharmaceutical companies from each country at the 'Bio International Convention 2024 (hereinafter referred to as Bio USA)' held in San Diego, USA from the 3rd to the 6th...According to the company, this year's event schedule included various discussions on each pipeline (new drug candidate) that was more advanced than before. In the case of Pexa-Vec, which completed phase 2a kidney cancer treatment, a business meeting was held with partner Regeneron. Senior officials from both companies attended and discussed licensing out (L/O) and development expansion....Sillajen announced that in addition to Pexa-Vec, it also held meetings about BAL0891 and SJ-600 series, which Sillajen is developing." "

Clinical • Licensing / partnership • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Gene therapy for people with hepatocellular carcinoma. (PubMed, Cochrane Database Syst Rev) - "The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking."

Clinical • Gene therapy • Journal • Review • Gastrointestinal Cancer • Gene Therapies • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Transplantation

Correlation of distinct circulating cytokine/chemokine profiles with clinical benefits of Pexa-Vec (thymidine kinase-deactivated vaccinia virus plus GM-CSF) and cemiplimab (REGN2810; anti-PD-1) in metastatic or unresectable renal cell carcinoma (mRCC). (ASCO 2024) - "Our findings suggest the potential utility of plasma cytokine and chemokine profiles in clinical benefits of mRCC patient to the combination of Pexa-Vec and cemiplimab, thereby aiding in future personalized treatment approaches."

Clinical • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CCL11 • CSF2 • IFNB1

Clinical efficacy of Pexa-Vec and Libtayo combination confirmed [Google translation] (whosaeng.com) - "Sillajen...will disclose the results of a follow-up analysis of phase 2 kidney cancer conducted jointly with Regeneron at the American Society of Clinical Oncology (ASCO), which will be held in Chicago, USA for 5 days from the 31st of this month....'The results of this study suggest the potential usefulness of plasma cytokine and chemokine profiles that indicate the clinical benefit of Pexa-Vec and cemiplimab combination treatment for mRCC patients, and may contribute to aiding personalized treatment approaches in the future.'"

P2 data • Kidney Cancer • Renal Cell Carcinoma

PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma. (PubMed, Liver Cancer) - "Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies."

Journal • Metastases • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Failure • Oncology • Solid Tumor

SillaJen Submits CSR to the US FDA for REN026 Study in Patients with RCC (Businesswire) - P1/2 | N=89 | NCT03294083 | Sponsor: SillaJen, Inc. | "SillaJen, Inc...has submitted CSR to the US FDA on 06 Feb 2024 for REN026, a phase 1b/2a dose escalation and safety/efficacy evaluation study of Pexa-Vec in combination with cemiplimab in patients with metastatic or unresectable renal cell carcinoma (RCC). The study demonstrated an acceptable safety profile and encouraging efficacy of the combination therapy of Pexa-Vec, an engineered oncolytic vaccinia virus, and Libtayo (cemiplimab), anti-PD-1 monoclonal antibody developed by Regeneron Pharmaceuticals Inc. (NASDAQ: REGN)."

P1/2 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide. (PubMed, Mol Cancer) - "Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10.Intra-tumoral administration of JX-594 in combination with cyclophosphamide and avelumab is safe and capable of modulating the TME in cold STS. However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS."

Biomarker • IO biomarker • Journal • Oncolytic virus • P2 data • Tumor microenvironment • Fatigue • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD8 • CXCL10

Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide (Mol Cancer) - P1/2 | N=197 | METROMAJX (NCT02630368) | "Fifteen patients were enrolled, with the most frequent toxicities being grade 1 fatigue and fever. Fourteen patients were assessable for efficacy analysis. At 6 months, only one patient remained progression-free, indicating that the trial did not meet the first stage endpoint of Simon’s design. Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10."

P2 data • Soft Tissue Sarcoma