Telomelysin (suratadenoturev) / Oncolys BioPharma, Medigen Biotech - LARVOL DELTA

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

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

NRG-GI007: Secondary endpoints of safety assessment and clinical complete response (cCR) of chemoradiation with endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer. (ASCO-GI 2025) - P1 | "The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that 58% of control arm Pts have locally persistent disease... In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 was added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fxs) for medically inoperable EC Pts with pathologically proven adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus or Siewert Type I/II gastroesophageal junction... OBP-301 + CRT is safe and the preliminary cCR rate compares favorably to the historical control from NRG/RTOG 0436. Updated safety and cCR data will be presented. A randomized study is being planned."

Clinical • Oncolytic virus • Esophageal Cancer • Gastrointestinal Cancer • Oncology • TERT

Announcement of OBP-301 presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium [Google translation] (Oncolys BioPharma Press Release) - P1 | N=16 | NCT04391049 | "We are pleased to announce that the results of a Phase 1 investigator-initiated clinical trial of OBP-301...This study enrolled a total of 15 patients, including 12 esophageal cancer patients and 3 gastroesophageal junction cancer patients...Preliminary efficacy was evaluated in 13 patients, as two of the 15 enrolled patients died before the therapeutic effect of this study could be confirmed...Efficacy was assessed by endoscopic findings and pathological biopsy, and the disappearance of tumors at the site of OBP-301 administration (clinical complete response: cCR) was confirmed in all 13 patients....'The results of this study not only show that OBP-301 can be safely combined with radiochemotherapy in the future, but also show an unprecedentedly high therapeutic effect with a 100% response rate. The 5-year survival rate for esophageal cancer is still not high, so we will continue to consider the next step in clinical trials...'"

P1 data • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma

Notification regarding the status of preparations for establishing a logistics system for the oncolytic virus OBP-301 [Google translation] (Nikkei) - "We are pleased to announce that we have established a system that complies with GCTP (Good Gene, Cellular, and Tissue-based Products Manufacturing Practice), a standard for manufacturing and quality control of regenerative medicine products, at the facility of Mitsui-Soko Holdings Co., Ltd. (hereinafter 'Mitsui-Soko HD') in Kobe City, Hyogo Prefecture, which is entrusted with the logistics operations of packaging, storage, and transportation of the oncolytic virus OBP-301 for which we are aiming to apply for approval...OBP-301 has completed the 'Phase 2 clinical trial for esophageal cancer combined with radiation (OBP101JP trial)'....We will continue to work with Mitsui-Soko HD to develop a stable and high-quality logistics system. We will also work hard to apply for approval of OBP-301."

Commercial • Trial completion • Esophageal Cancer

Oncolys Grants Telomelysin Commercial Rights to Medigen in Taiwan (Pharma Japan) - "Tokyo-based biotech Oncolys BioPharma said on December 20 that it is granting the rights to market its investigational oncolytic virus telomelysin in Taiwan to its long-term local partner Medigen Biotechnology."

Commercial • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • Squamous Cell Carcinoma of Head and Neck

Notice regarding outlook for approval of OBP-301 in Japan [Google translation] (Nikkei) - "We have been conducting advance consultations with the Pharmaceuticals and Medical Devices Agency...regarding clinical, non-clinical, and quality. As a result, we have agreed with PMDA to start 'Sakigake Comprehensive Evaluation Consultations' prior to the domestic approval application of OBP-301. We plan to start 'Sakigake Comprehensive Evaluation Consultations' in the first half of 2025...The 'Sakigake Comprehensive Evaluation Consultation' will evaluate not only the results of numerous clinical trials conducted to date, but also the detailed content of clinical trial plans to be implemented after marketing. In addition, non-clinical trials and quality will also be evaluated in sequence. After these evaluations are completed, OBP-301 is expected to be applied for approval, approved, listed on the drug price list, and released for sale. At this stage, the goal is to apply for approval of OBP-301 in the fiscal year ending December 2025."

Japan filing • Solid Tumor

Notice regarding business license application for regenerative medicine product manufacturers and distributors [Google translation] (Oncolys BioPharma Press Release) - "Our company has applied to the Tokyo Metropolitan Government for business license as a manufacturer and distributor of regenerative medicine products...We are currently in discussions with the Pharmaceuticals and Medical Devices Agency. In the future, OBP-301 will be approved as a regenerative medicine product. Once approved, we will be positioned as the manufacturer and distributor responsible for shipping OBP-301 within Japan...Therefore, we have received the GQP (Good Quality Practice) from the Tokyo Metropolitan Government. Compliance with 'GVP (Good Vigilance Practice)' and 'GVP (Good Vigilance Practice: Standards for post-marketing safety management)'. It is necessary to undergo an examination regarding which requirements and obtain permission to manufacture and sell regenerative medicine products."

Commercial • Oncology • Solid Tumor

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

Announcement of the conference presentation of oncolytic virus OBP-301 at the 62nd Annual Meeting of the Japanese Society for Cancer Therapy [Google translation] (Nikkei) - "The Company conducted a Phase 2 study (hereinafter referred to as the 'OBP101JP study') using oncolytic virus OBP-301 in combination with radiotherapy, with the aim of developing a new treatment method for locally advanced esophageal cancer. At the organ-specific symposium of the 62nd Academic Meeting of the Japanese Society for Cancer Therapy, which will be held from October 24th (Thursday) to October 26th (Saturday), 2024, Dr. Koki Watanabe, Department of Gastroenterology, Kitasato University School of Medicine, will be speaking. We would like to inform you that an academic conference presentation will be held regarding the results of the OBP101JP exam."

P2 data • Esophageal Cancer • Oncology • Solid Tumor

Announcement regarding the status of system development for proper post-marketing use of oncolytic virus OBP-301 [Google translation] (Nikkei) - "Regarding the oncolytic virus OBP-301, for which the Company aims to apply for approval, the Company has entered into a safety information agreement...that stipulates the handling of safety information generated after marketing in the medical field. We would like to inform you that we have decided to enter into an agreement with Fujifilm Toyama Chemical Co., Ltd...Clinical trials conducted before an application for approval are conducted on a limited number of patients based on the clinical trial protocol. On the other hand, after marketing, the drug will be administered to patients of various ages, medical conditions, complications, concomitant medications, etc., so there is a possibility that safety issues that were not recognized in clinical trials may arise....Based on this agreement, the Company will establish a system to promote the proper use of OBP-301....and promptly respond to the Pharmaceuticals and Medical Devices Agency in accordance with regulations."

Licensing / partnership • Oncology • Solid Tumor

[Announcement] The first phase of the clinical trial of OBP-301, a new drug developed in China, initiated by the host of the United States and combined with chemotherapy and radiotherapy for the treatment of esophageal cancer, has completed the enrollment of subjects. [Google translation] (stock.yahoo) - "Oncolys announced today (August 06, 2024) that the new viral drug OBP-301 (Telomelysin) will be implemented in the United States...The first phase clinical trial of OBP-301 combined with chemoradiotherapy for the treatment of esophageal cancer...initiated by the host has been completed...A total of 15 subjects were included...The target patients of this trial are patients with inoperable esophageal cancer or gastroesophageal junction (GEJ) cancer...After demonstrating safety in a dose finding cohort trial involving 6 subjects, the number of the expansion cohort included 9 subjects to further evaluate the combination of OBP-301 and chemoradiation therapy safety and preliminary effectiveness. This trial hopes to obtain OBP-301 and combine it with chemotherapy and radiotherapy in cases where treatment is not possible."

Enrollment closed • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

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

NRG-GI007: Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: NRG Oncology | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Surgery • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Keya's OBP-301 has enrolled the first subject in a Phase II clinical trial initiated by researchers in the United States. [Google translation] (MoneyDJ) - "The new drug under development OBP-301 is in the United States. The researcher initiated the second phase of clinical trials and enrolled the first subject...Gene Biotechnology and Japanese listed company Oncolys Oncolys announced today (June 03, 2024), a new oncolytic virus drug OBP-301 (Telomelysin) jointly developed by BioPharma...that OBP-301 combined immune checkpoint inhibition was performed at Cornell University in the United States. Researchers of the drug to treat gastric cancer and gastroesophageal junction cancer...patients with anti-PD-1/PD-L1 antibodies initiated a phase 2 clinical trial and enrolled the first subject....The purpose of this trial is to verify the effectiveness and safety of using OBP-301 in combination with an immune checkpoint inhibitor (pembrolizumab) in patients with gastric cancer and gastroesophageal junction cancer who are resistant to immune checkpoint inhibitor treatment. It is expected that the maximum 27 patients were included."

Enrollment open • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of Suratadenoturev (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: Weill Medical College of Cornell University | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

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

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

Study of Suratadenoturev (OBP-301) in Combination With Pembrolizumab in Esophagogastric Adenocarcinoma (clinicaltrials.gov) - P2 | N=27 | Not yet recruiting | Sponsor: Weill Medical College of Cornell University

New P2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus. (PubMed, PLoS One) - "For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication...OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas."

Journal • Oncolytic virus • Infectious Disease • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TERT

Genya: The sales cooperation agreement for the development of new Chinese medicine OBP-301 in Japan has been signed [Google translation] (MoneyDJ) - "Gene Biotechnology and Japanese listed company Oncolys BioPharma...jointly developed Oncolys announced today (February 7, 2024) that OBP-301 (Telomelysin), a new oncolytic virus drug, has reached an agreement with Japan's FUJIFILM Toyama Chemical Co., Ltd. (hereinafter referred to as FUJIFILM Toyama Chemical) for OBP-301. In the cooperation agreement for sales in Japan, Oncolys will be responsible for OBP-301 application for marketing approval and supply of OBP-301 in the future, and FUJIFILM Toyama Chemical will be responsible for sales and promotion to medical institutions. This agreement is a sales cooperation agreement and there is no upfront. However, if the marketing approval and predetermined sales targets are achieved in the future, Oncolys can receive a maximum cumulative milestone payment of 1.7 billion yen."

Licensing / partnership • Oncology • Solid Tumor

Initial safety assessment of the endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer: NRG-GI007. (ASCO-GI 2024) - P1 | "The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that about half of Pts have locally persistent disease...OBP-301 was previously studied with RT in Japanese esophageal cancer Pts and shown to be safe and has promising activity.1 In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 is added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fractions) for Pts with medically inoperable EC... No DLTs in the 6 evaluable Pts were observed and it is concluded that the initial OBP-301 dose level is safe. NRG-GI007 was reopened on August 7, 2023 to the expansion cohort. Full toxicity and treatment data will be presented."

Clinical • Oncolytic virus • Esophageal Cancer • Gastrointestinal Cancer • Oncology • TERT

Announcement of Investigator-Initiated Phase 2 Clinical Trial Agreement For Immunotherapy refractory Esophagogastric adenocarcinoma (Oncolys BioPharma Press Release) - "Oncolys BioPharma Inc...is pleased to announce that the investigator-initiated Phase 2 clinical trial (hereinafter 'this clinical trial') agreement with Weill Cornell Medicine, for Immunotherapy refractory Esophagogastric adenocarcinoma has been executed. This clinical trial is led by Dr. Manish Shah...This agreement establishes a collaborative development framework for Suratadenoturev (OBP-301) and Pembrolizumab among three parties: Oncolys, Weill Cornell Medicine and Merck & Co., Inc.'s ('Merck'). Costs of this study will be shared between Oncolys and Merck....This new phase II multi-center clinical study of suratadenoturev (OBP-301) with an anti-PD-1 therapy in an immunotherapy (IO) refractory advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma patients, targets an important unmet need in drug development."

Licensing / partnership • New P2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

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