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

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

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

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

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma. (PubMed, Cancer Cell Int) - "The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity."

Journal • Metastases • Oncolytic virus • Genito-urinary Cancer • Hepatology • Liver Failure • Oncology • Renal Cell Carcinoma • Solid Tumor

Sillajen's shares soar 30% after positive trial results for Pexa-Vec+Libtayo combo in renal cell carcinoma (Korea Biomedical Review) - P1b/2a | N=89 | NCT03294083 | Sponsor: SillaJen, Inc. | "Sillajen's shares shot up a daily limit of 30 percent to trade at 5,590 won ($4.3) on Monday afternoon, after filing on Friday results of a phase 1b/2a clinical study on Pexa-Vec, a thymidine kinase-deactivated vaccinia virus, combined with Regeneron's checkpoint inhibitor, Libtayo (cemiplimab), for metastatic or unresectable renal cell carcinoma (RCC)....In Arm C treated with the combo in patients not previously treated with immune checkpoint inhibitors, the objective response rate (ORR), the percentage of tumors that shrank in size or disappeared completely, was 23.3 percent and the overall survival (OS) was 25.1 months. Both ORR and OS were the highest compared to other patient groups."

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

Pexa-vec (thymidine kinase-deactivated vaccinia virus plus GM-CSF) in combination with cemiplimab (REGN2810; ANTI-PD-1) for metastatic or unresectable renal cell carcinoma REN026: Results from a phase II study (ESMO 2023) - P1b/2a | "The most common treatment-related adverse event was pyrexia, with a Grade ≥ 3 of 13.3% in Arm A, 0% in Arm B,0% in Arm C, and 3.6% in Arm D. No Grade 5 events occurred in any of the study arms. Table: 1885P Summary of efficacy results Conclusions The combination immunotherapy of IV PV and cemiplimab demonstrated an acceptable safety profile and encouraging efficacy of ORR and survival with durable responses in patients with metastatic or unresectable RCC, regardless of previous ICI treatment."

Combination therapy • Metastases • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CSF2

A Phase I/II Study of Pexa-Vec Oncolytic Virus in Combination With Immune Checkpoint Inhibition in Refractory Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=34 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Checkpoint inhibition • Combination therapy • Oncolytic virus • Trial completion • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KRAS

Korean pharma firms gear up for ESMO 2023, Europe's premier cancer conference (Korea Biomedical Review) - "As the opening of the European Society for Medical Oncology Annual Meeting (ESMO 2023), Europe's largest cancer conference, draws near, attention here is focused on Korean participants....Sillajen will present results from a phase 2 study of kidney cancer patients treated with its anticancer virus Pexavec in combination with Regeneron's immuno-oncology drug Libtayo (cemiplimab). The company will also present the phase 1 design of BAL0891, a new pipeline acquired from Basilea in Switzerland last year."

Clinical protocol • P2 data • Renal Cell Carcinoma

Oncolytic virotherapies for pediatric tumors. (PubMed, Expert Opin Biol Ther) - "We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future."

Journal • Oncolytic virus • Review • Herpes Simplex • Infectious Disease • Measles • Oncology • Pediatrics • Solid Tumor

Scientists discover virus that kills cancer cells, could help develop anti-cancer vaccines [Google translation] (163.com) - "Scientists from the University of California-San Francisco (USA) present research data on how viral infections interact with the immune system to fight cancer cells. The study highlights the ability to combine this form of treatment with existing cancer treatments....Early observations suggested that Pexa-Vec could destroy tumors by destroying the blood vessels that feed it. Now researchers suggest the virus could be treated intravenously. This is an important difference between Pexa-Vec and other viruses capable of killing cancer cells, as they can only be injected directly into tumors, which limits their therapeutic potential."

Preclinical • Oncology

K-Bio to participate in ESMO2023… Latest cancer treatment and diagnosis technology unveiled in Europe [Google translation] (E-Today) - "In addition, EDGC (Eone Diagnomics) plans to disclose the efficacy of its anticancer drug candidates 'EC-352H' and 'EC-374H' on lymphatic cancer, and SillaJen announced the results of a study on Pexa-Vec and Libtayo combination therapy for kidney cancer and 'BAL0891' research overview."

Clinical data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor