pfifteloxin (OBP-702) / Oncolys BioPharma - LARVOL DELTA

Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702). (PubMed, Int J Clin Oncol) - "Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy."

First-in-human • IO biomarker • Journal • Review • Tumor mutational burden • Oncology • Pancreatic Cancer • Solid Tumor • CAFs • CDKN1A • E2F1 • KRAS • TMB • TP53

Collagen depletion by pirfenidone enhances antitumor effect of oncolytic adenovirus against peritoneal metastases of gastric cancer. (PubMed, Mol Ther Oncol) - "Cancer-associated fibroblasts (CAFs) play a crucial role in collagen accumulation, which develops and promotes peritoneal metastasis (PM) in gastric cancer (GC). PFD suppressed collagen production in PM and improved viral penetration into the tumors, which enhanced the antitumor effects of OBP-702 against PM of GC. Collagen depletion by PFD enhances the penetration of OBP-702 into PM of GC, in turn enhancing the antitumor effects of OBP-702 against PM of GC."

IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CAFs

P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors. (PubMed, Anticancer Res) - "Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS."

IO biomarker • Journal • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • PD-L2

Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING. (PubMed, Cancer Immunol Immunother) - "These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • STING • TP53

p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis. (PubMed, Cancer Gene Ther) - "We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine. (PubMed, NPJ Vaccines) - "Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • IL4 • ITGAX

Development of Oncolytic Virus Immunotherapy to Improve the Immunosuppressive Microenvironment in Pancreatic Cancer (PubMed, Gan To Kagaku Ryoho) - "We developed an oncolytic adenovirus, OBP-702, carrying the tumor suppressor gene p53, and report its therapeutic potential to induce cytopathic effects and activate antitumor immunity via p53 induction. In the present study, we investigated the therapeutic potential of epigenetic modulators in oncolytic viral immunotherapy combined with a dendritic cell vaccine."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • TP53

A novel systemic delivery approach for oncolytic adenovirus therapy using tumor-homing mesenchymal stem cells (AACR 2025) - "We previously developed a telomerase-specific OV, Telomelysin (OBP-301), which utilizes the hTERT promoter to drive the expression of E1A and E1B. When MSCs loaded with OBP-702 (MSC-OBP-702) were intraperitoneally injected into an MC38-bearing peritoneal metastasis model, they effectively migrated to metastatic sites, significantly suppressing tumor growth and improving overall survival compared to OBP-702 alone. These findings demonstrate that MSC-OBP-702 has significant potential to overcome the challenges of systemic OV therapy through the tumor-homing capability of MSCs, providing a foundation for future clinical applications."

IO biomarker • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor

A novel combined immunotherapy of gut microbial metabolite butyrate and oncolytic adenovirus in colorectal cancer (AACR 2025) - "The combination therapy of CBM588 and OBP-702 demonstrated similar synergistic antitumor effects in mouse subcutaneous and rectal tumor models. In conclusion, the combination of OBP-702 and butyrate shows promise as a synergistic antitumor strategy and may represent a novel therapeutic approach for colorectal cancer."

IO biomarker • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • TP53

Preoperative p53-armed oncolytic virus therapy enhances the efficacy of postoperative adjuvant ICI therapy (AACR 2025) - "We have developed a telomerase-specific oncolytic virus (OV), OBP-301, and its p53 gene-armed derivative, OBP-702. Bulk RNA-seq of OV treated MC38 tumor with reactome pathway analysis revealed the upregulation of pathways associated with enhanced antitumor immunity.Conclusion : OV therapy not only demonstrated direct antitumor effects but also induced tumor-specific systemic immunity and sustained long-term immune activation. These results suggest that preoperative OV therapy can enhance the effectiveness of postoperative ICI therapy."

Clinical • IO biomarker • Oncolytic virus • Colon Cancer • Colorectal Cancer • Microsatellite Instability • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • MSI

Boosting oncolytic virus-mediated antitumor immunity by dendritic cell vaccine therapy via p53-activated immune response (AACR 2025) - "Our data suggest that immunization with p53-expressing virus-transduced DCs enhances the antitumor efficacy of p53-armed oncolytic adenovirus OBP-702 in murine colorectal cancer models via induction of p53-specific antitumor immune responses."

IO biomarker • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CD86 • CSF2 • IL4 • ITGAE • ITGAX

Autophagy inhibition enhances the antitumor effect of p53-armed oncolytic virotherapy against pancreatic cancer (AACR 2025) - "Our data suggest that autophagy inhibition by CQ enhances the induction of apoptosis and ICD by OBP-702 and the level of MHC-I expression on PDAC cells, probably promoting the antitumor immune responses against PDAC cells. Therefore, we are currently evaluating the combined effect of CQ and OBP-702 using the syngeneic PAN02 subcutaneous tumor models."

IO biomarker • Oncolytic virus • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Combined Efficacy of Dendritic Cell Vaccine and Oncolytic Adenovirus in Colorectal Cancer (PubMed, Gan To Kagaku Ryoho) - "We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction. In this study, we investigated the combined effect of p53-transduced DC vaccine and OBP-702 in colorectal cancer."

Journal • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor • TP53

Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity. (PubMed, Cancer Immunol Immunother) - "We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect."

IO biomarker • Journal • Oncolytic virus • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD63 • CD8 • CD80 • CD83 • CD86 • IFNG

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. (PubMed, Mol Ther Oncol) - "Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS."

Immunogenic cell death • Journal • Oncolytic virus • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8 • HMGB1

Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer. (PubMed, Mol Ther Oncol) - "Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC."

IO biomarker • Journal • Oncolytic virus • Gastric Cancer • Gastrointestinal Cancer • Oncology • Peritoneal Cancer • Solid Tumor • CD163 • CD8

p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression. (PubMed, Acta Med Okayama) - "We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors."

Journal • Oncolytic virus • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • BCL2L1 • TP53

Gut microbial metabolite butyrate facilitates antitumor efficacy of telomerase-specific oncolytic adenovirus via MHC-I and cGAS-STING pathway activation (AACR 2024) - "Butyrate and OBP-702 showed synergistic antitumor effects via activation of systemic antitumor immunity in addition to direct effects of butyrate on viral cytotoxic potential, which provides valuable insights into the development of innovative cancer treatment strategies."

Clinical • IO biomarker • Oncolytic virus • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • TP53

Combination of CDK4/6 inhibitor promotes the antitumor effect of oncolytic adenovirus against canine breast cancer cells (AACR 2024) - "The combination of palbociclib and OBP-301 showed a more profound antitumor effect compared with monotherapy against CMT-U27 and AZA-CB cells. Our results suggest that telomerase-specific oncolytic adenoviruses have cytopathic effect against canine breast cancer cells via virus infection and replication. Furthermore, combination of CDK4/6 inhibitor may be a promising strategy for promoting the antitumor effect of oncolytic adenovirus against canine breast cancers."

Oncolytic virus • Breast Cancer • Oncology • Solid Tumor • TP53

Utility of oncolytic virus as an immunostimulants and potential for combination therapy with ICIs (AACR 2024) - "Among our oncolytic adenoviruses (OVs), OBP-301, in which the human telomerase reverse transcriptase (hTERT) promoter element drives the expression of the viral E1A and E1B genes, is currently undergoing clinical trials. The OVs showed potent and long-term immune activation by inducing CD8 and TRM in tumors as well as direct anti-tumor effects, and synergistic effects with ICI."

Combination therapy • IO biomarker • Oncolytic virus • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD44 • CD8 • TERT • TP53

Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus. (PubMed, Br J Cancer) - "OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer."

Journal • Oncolytic virus • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • TP53

Therapeutic Effect of Oncolytic Adenovirus on Pancreatic Cancer Stroma (PubMed, Gan To Kagaku Ryoho) - "We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF."

Journal • Oncolytic virus • Stroma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • TP53

p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells. (PubMed, PLoS One) - "In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis."

Journal • Oncolytic virus • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • DLD • EGFR • KRAS

Oncolys Research Memo (9): Policy to continue development of next-generation telomelysin within the scope of the grant [Google translation] (Yahoo Finance) - "'OBP-702' was selected as an AMED grant project, and research and development has been carried out mainly by a research group at Okayama University....However, the phase 1 trial was not adopted because it was determined that monotherapy was preferable to combination therapy, and as a result, the clinical trial in 2023 was postponed. In 2024, it seems likely that the company will reapply to AMED for monotherapy with OBP-702. In the US, it is possible to conduct phase 1 clinical trials using combination therapy with immune checkpoint inhibitors, but the company's current financial situation makes it difficult to conduct it alone. In addition, when looking for a joint development partner, it is important to obtain POC in humans, so the company must proceed with phase 1 clinical trials on its own."

New P1 trial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer. (PubMed, Cancer Immunol Immunother) - "Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation."

IO biomarker • Journal • Myeloid-derived suppressor cells • Oncolytic virus • Gastrointestinal Cancer • Hepatology • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CSF2 • TP53