Delving into the Latest Updates on Recombinant human GM-CSF oncolytic herpes simplex virus type 2 (Binhui Bio) with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

OH2 Oncolytic Viral Therapy, rHSV2hGM-CSF

+ [5]

Target

CSF-2R

Mechanism

CSF-2R stimulants(Granulocyte-macrophage colony-stimulating factor receptor stimulants)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesDigestive System Disorders+ [6]

Active Indication

MelanomaColorectal Liver MetastasesBladder Cancer+ [15]

Inactive Indication

Advanced Colorectal AdenocarcinomaPancreatic Cancer

Originator Organization

Wuhan Binhui Biopharmaceutical Co., Ltd.

Active Organization

Wuhan Binhui Biopharmaceutical Co., Ltd.

Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationFast Track (US), Orphan Drug (US), Breakthrough Therapy (CN)

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Author: Hu, Han ; Peng, Yichen ; Li, Wenbin ; Yu, Jianyu ; Song, Lairong ; Li, Xiaojie ; Wang, Liang ; Zhang, Botao ; Xie, Lei ; Wang, YaLi ; Zhu, Sipeng ; Zheng, Yi ; Ji, Qiang ; Zhang, Ziyi ; Chen, Feng ; Wu, Zhen ; Yu, Chunna ; Fang, Aizhong ; Wang, Xiaomin ; Zhou, Lili ; Lin, Yi ; Liu, Binlei ; Xu, Xiaoying

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4⁺ and CD8⁺ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

01 Jan 2023·Pharmacological Research

Transarterial viroembolization improves the therapeutic efficacy of immune-excluded liver cancer: Three birds with one stone

Article

Author: Kan, Xuefeng ; Zheng, Chuansheng ; Ouyang, Tao ; Cai, Linkang ; Liu, Binlei ; Cao, Yanyan ; Yang, Junhan ; Wang, Runyang ; Xiong, Fu ; Liang, Bin ; Guo, Xiaopeng

OBJECTIVETo investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models.MATERIALS AND METHODSSubcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured.RESULTSThe optimal viral titer of OH2 was 1 × 10⁷ CCID₅₀. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies.CONCLUSIONTAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice.DATA AVAILABILITYData is available from the corresponding author upon requirement.

01 Nov 2022·Cancer MedicineQ3 · MEDICINE

A novel oncolytic virus induces a regional cytokine storm and safely eliminates malignant ascites of colon cancer

Q3 · MEDICINE

ArticleOA

Author: Cai, Qian ; Zhou, Fuxiang ; Dong, Shuang ; Zhong, Yi ; Liu, Binlei ; Wang, Jun ; Qian, Yu ; Guo, Fang ; Zhang, Siqi ; Hu, Sheng

AbstractBackgroundGiven malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity.MethodsWe established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single‐cell RNA sequencing. Furthermore, anti‐interleukin (IL)‐6R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL‐6 hypersecretion.ResultsOH2 was able to eliminate ascites and significantly prolong the survival of mice‐bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro‐inflammatory cytokines, mainly IL‐6, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5‐fluorouracil or nonresponders. Furthermore, the initial‐stage blocking of the IL‐6 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single‐cell RNA sequencing.ConclusionsOH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL‐6, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy.

100 Deals associated with Recombinant human GM-CSF oncolytic herpes simplex virus type 2 (Binhui Bio)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 3	CN	Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch	23 Feb 2023
Colorectal Liver Metastases	Phase 2	CN	Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch	20 Oct 2022
Non-Muscle Invasive Bladder Neoplasms	Phase 2	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	11 Jul 2022
Bladder Cancer	Phase 2	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	25 May 2022
Locally Advanced Bladder Carcinoma	Phase 2	CN	Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch	23 May 2022
Metastatic Neoplasm to the Bladder	Phase 2	CN	Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch	23 May 2022
Central Nervous System Neoplasms	Phase 2	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	16 Nov 2021
Advanced Colorectal Adenocarcinoma	Preclinical	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	17 Oct 2023
Colorectal Cancer	Preclinical	CN	Wuhan Binhui Biotechnology Co., Ltd. Biological Innovation Park Branch	17 Oct 2023
Pancreatic Cancer	Preclinical	CN	Wuhan Binhui Biopharmaceutical Co., Ltd.	02 Feb 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04616443 (Corporate Publications) Manual	Phase 1	Melanoma	-	OH2	(uderzwhatr) = fkttcdgyiq pnlntjagkl (vzsieypcmm )	Positive	06 Nov 2022
NCT04616443 (Corporate Publications) Manual	Phase 1	Melanoma	-	OH2 (接受PD-1治疗失败且疾病分期为III-IVM1a的亚组人群)	(uderzwhatr) = mvfafzesws pnlntjagkl (vzsieypcmm )	Positive	06 Nov 2022
NCT04386967 (ASCO2022) Manual	Phase 1	Unresectable Melanoma	35	OH2	(ymfzmijwtk) = xipkuykowp lsthyrsdvi (cgwrrppatq ) View more	Positive	02 Jun 2022