Chinese Biotechs Shine at ESMO 2024 with Breakthrough CAR-T, mRNA Cancer Vaccines, and Oncolytic Virus Therapies

ESMO is the largest multidisciplinary conference in the European oncology field.The 2024 European Society for Medical Oncology (ESMO) will be held in Barcelona, Spain, from September 13, 2024, to September 17, 2024.

At this ESMO conference,Unicar-Therapy, ClearPath Biotherapeutics, Rongrui Pharmaceuticals, Virogin Biotech, WestGene Biotech, Akeso Biopharma, Hengrui Medicine, Promab BiotechnologiesChinese companies have brought their painstakingly developedInnovative drugs such as cell therapy, oncolytic viruses, mRNA tumor vaccines, and bispecific antibodiesDebut. They will unveil the latest clinical trial results of these drugs on this global stage, aiming to deliver a strong voice of Chinese innovation to the world.

QH104 is developed byQinghui LianuoIndependently developed a B7H3-targetedAllogeneic Universal TypeCAR-γδ T CellsMedicine,ItsProduction costs are significantly reduced compared to autologous cell therapy, enhancing clinical accessibility.

Results from the first-in-human clinical trial of QH104 in recurrent glioblastoma (rGBM) indicate that QH104 has a favorable safety profile, with observed clinical benefits in the rGBM patient population supporting further clinical development.At this ESMO conference, the clinical data of QH104 will be disclosed for the first time.

The development of QH104 is based on the成果 published in《Nature》by Qinghui Lianuo in collaboration with Tsinghua University — “Revealing the γδ T cell immune recognition mechanism”.

γδ T cells, as a unique subset of T cells, combine adaptive and innate immune functions, enabling precise recognition and elimination of tumor cells. Unlike αβ T cells, which rely on MHC peptide recognition,γδ T cells have a unique recognition method:It can recognize specific metabolic products IPP/DMAPP produced by tumor cells. These substances, known as "phosphoantigens," bind to butyrophilins (especially proteins of the BTN family), inducing the exposure of butyrophilin epitopes extracellularly and enabling γδ T cells to rapidly identify tumor and infected cells.

This mechanism also enables γδ T cells to be applied in allogeneic settings, avoiding the risk of graft-versus-host disease (GvHD).Moreover, γδ T cells possess the natural ability to home to various tissues, thereby demonstrating greater potential than αβ T cells in immune surveillance and the clearance of solid tumors.

Currently, ssCART-19 has been CDEIncluded in the breakthrough therapy category, andReceived FDA Orphan Drug Designation in the United States.

OVV-01 isRongrui PharmaceuticalsSelf-developedWorld's FirstThe attenuated recombinant virus of vesicular stomatitis oncolytic virus (VSV), which is developed based on Rongrui Pharmaceuticals' globally patented new drug development platform OVV-Drive-IO. The platform's mechanism of action is "target + kill," addressing challenges in immunotherapy.The two major pain points: poor efficacy of single-agent therapy and the inability to treat due to the absence of a target.

Target:Oncolytic virus vaccine (OVV) carrying tumor antigens enables tumor cells to specifically express tumor-associated antigens or specific antigens (TAA/TSA), targeting tumor cells.Transform tumors that cannot be targeted into targetable ones.

By targeting tumor cells,Oncolytic viruses can break through the barriers of CAR-T cell therapy for solid tumors, thereby expanding the indications of anti-tumor drugs tenfold.City of Hope Hospital in the United States used oncolytic viruses to express the blood cancer CD19 target on solid tumor cells in mice, and treated solid tumors with a combination of blood cancer CD19-targeted CAR-T therapy. As a result, 60% of the mice experienced complete regression of their solid tumors.

Hunting:After targeting tumor cells, use anti-tumor drugs that target the tumor antigen to identify tumor cells, lyse and kill the tumor.The rupture of tumor cells releases more viruses, and more viruses infect more tumor cells.This triggers a chain reaction, achieving a therapeutic effect of 1+1>2. In animal experiments, the combination of oncolytic virus therapy and immune cell therapies such as CAR-T/TCR-T can achieve efficacy.90%The above.

VG201 is based onFornova HealthA potential First-in-class HSV-1 oncolytic virus candidate product constructed using a self-developed transcription and translation dual-regulation (TTDR) backbone exhibits enhanced oncolytic activity against tumors with specific expression of carcinoembryonic antigen (CEA). It also produces immune-stimulating cytokines IL-12 and IL-15/IL15Rα, thereby modulating the tumor microenvironment.In addition, VG201 is expected to becomeThe FirstTargeted Oncolytic Virus Therapy Based on Tumor Biomarkers.

In addition, VG201, based on the Synerlytic™ technology platform of Virogin Biotech, carries multiple exogenous genes in the hope of synergistically activating innate and adaptive anti-tumor immunity.

The preliminary results of VG201 study confirmed the clinical safety of VG201 and preliminarily showed encouraging tumor efficacy: As of 20April 24,Among 15 evaluable patients, 3 partial responses (PR) and 8 stable diseases (SD) were observed.; Tumor shrinkage was also observed in lesions that were not injected.

Currently, the Phase I clinical trial of VG201 is being conducted at two sites: the First Affiliated Hospital of Zhejiang University School of Medicine in China and the MD Anderson Cancer Center at the University of Texas in the United States.

It is worth mentioning that Virogin Biotech, as one of the few biotechnology companies globally that simultaneously possesses both next-generation oncolytic virus technology and mRNA technology dual platforms,Developing Oncolytic Virus + mRNA Vaccine Combination Therapy(Prime-Boost), which can fully leverage the complementary advantages of oncolytic viruses and mRNA tumor vaccines, working "from within and without" to seek systemic and synergistic activation of anti-tumor immunity.

WGc-043 is produced in China byWisgen BioIndependently developed,The world's first mRNA vaccine for the treatment of EB virus-positive tumors to receive IND approval in both China and the United States.

WGc-043 can activate the patient's own anti-tumor immunity,In vivo generation of cytotoxic T cells that kill tumors, antigen-specific antibodies, and memory T cells,Equivalent to the combined anti-tumor effects of CAR-T and monoclonal antibodies, it can also prevent tumor recurrence. It demonstrates highly efficient anti-cancer effects and superior safety.

WGc-043 has completed investigator-initiated trials (IIT) for nasopharyngeal carcinoma and natural killer T-cell lymphoma, with preliminary data showing good safety and efficacy.These two types of indications are currently the难点 (difficult points) in the clinical treatment of EB virus-related tumors.

The innovative aspects of WGc-043 include:

1) AI-Assisted Antigen Screening: Using AI to screen the broadest and safest protein sequences, and introducing a globally unique immune enhancer (IE) in mRNA molecules to activate patients' anti-tumor immunity. This generates cytotoxic T lymphocytes (CTL), antigen-specific antibodies, and memory T cells, providing highly efficient anti-cancer effects comparable to combination therapies involving CAR-T and monoclonal antibodies, while preventing tumor recurrence.

2) Advanced delivery system: The newly developed LNP delivery system has been patented in China, the United States, Europe, and other regions, and has demonstrated its safety and delivery efficiency in clinical trials of the product.