Biosyngen’s CAR-T Therapy BRG01 Cleared for Pivotal Trial in EBV-Positive Nasopharyngeal Carcinoma in China

Biosyngen’s chimeric antigen receptor T-cell (CAR-T) therapy BRG01 has been cleared by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for a pivotal phase 2 clinical trial in patients with Epstein-Barr virus (EBV)-positive relapsed/metastatic nasopharyngeal carcinoma.¹

BRG01 is engineered to target the EBV antigen, which is frequently expressed on nasopharyngeal carcinoma tumor cells. Patients with advanced nasopharyngeal carcinoma have previously been treated with BRG01 in the context of a phase 1 clinical trial (NCT05864924) in China and the United States. As of January 2024, the phase 1 trial had completed enrollment and dosing of patients. Nine patients, all of whom had received at least 1 prior treatment with an immune checkpoint inhibitor, finished undergoing assessments for dose-limiting toxicity and preliminary efficacy in the trial. Biosyngen noted that on PET-CT scans 75% of the patients who were treated at the high-dose in the study demonstrated local tumor shrinkage and reduced metabolic activity, with some showing complete remission of tumor lesions. The company also reported that BRG01 exhibited potent antiEBV activity in the form of significant decreases in EBV viral load in the peripheral blood. Biosyngen also characterized the CAR-T as having shown “excellent safety” in initial data from the trial.

"The approval of the phase 2 clinical trial for BRG01 is a testament to the robust preclinical data and strong early clinical results observed with this innovative therapy" Zhang Li, MD, MSc, the director of the Phase I Ward at the Sun Yat-Sen University Cancer Center and Deputy Director of the Lung Cancer Research Institute at Sun Yat-sen University, and principal investigator for the BRG01 clinical trial, said in a statement.¹ "BRG01 has the potential to be a first-in-class T-cell therapy for EBV-positive tumors, and we are confident in its ability to deliver meaningful clinical benefits to patients with this difficult-to-treat malignancy.”

The FDA previously granted orphan drug designation to BRG01 on June 6, 2023, and fast track designation on July 10, 2023.^2,3 Investigational new drug (IND) application clearance for the phase 1 trial was obtained from the FDA in February 2023. The aforementioned phase 1 trial in China was cleared earlier by the NMPA’s CDE in December 2022. Notably, in April 2023 Biosyngen also received clearance from both the FDA and CDE for phase 1 clinical trials for BRG01 in a new indication: EBV-positive lymphoma. According to the company, the trials in EBV-positive lymphoma are currently in progress.

"The approval of BRG01 for a pivotal phase 2 clinical trial is a major milestone for Biosyngen and underscores our commitment to developing innovative cell therapies to address significant unmet needs in solid tumors,"Michelle Chen, PhD, the cofounder and chief executive officer of Biosyngen, added to the statement.¹ “We plan to continue investing in research and development to expedite the clinical progress and market availability of BRG01, offering more effective treatment options for patients worldwide.”

In addition to BRG01, Biosyngen is also developing BRL03, T-cell receptor T-cell (TCR-T) therapy, for the treatment of solid tumors.⁴ Notably, in September 2023, the company received clearance of an IND application from the FDA for a phase 1/2 clinical trial for BRL03 in lung cancer, gastric cancer, and other advanced solid tumors. BRL03’s development was supported by the use of its IDENTIFIER technology platform that discovers and identifies antigens, antibodies, and TCRs. The company selected TCRs with high specificity and affinity for a wide range of solid tumors with the IDENTIFIER platform to target a broad patient base. Biosyngen has 1 other cell therapy currently in the clinical stage: BST02, a tumor infiltrating lymphocyte therapy being evaluated in a phase 1 clinical trial (NCT06173726) for the treatment of liver cancer.¹

REFERENCES
1. Biosyngen’s BRG01 enters phase II clinical trial, A first-in-kind autologous EBV-specific CAR-T therapy for solid tumors on recurrent/metastatic nasopharyngeal carcinoma. News release. Biosyngen. July 16, 2024. Accessed July 17, 2024. https://firstwordpharma.com/story/5876299
2. Biosyngen’s first-in-class cell therapy BRG01 receives FDA Fast Track designation. News release. Biosyngen. July 10, 2023. Accessed July 17, 2024. https://www.biosyngen.com/index.php?m=home&c=View&a=index&aid=107
3. Biosyngen's Cell Therapy BRG01 Granted Orphan Drug Designation by the U.S. FDA for Treatment of Nasopharyngeal Cancer. News release. Biosyngen. June 6, 2023. Accessed July 17, 2024. https://www.asiaone.com/business/biosyngens-cell-therapy-brg01-granted-orphan-drug-designation-us-fda-treatment
4. Biosyngen received FDA approval for Phase I/II Clinical Trials for BRL03, targeting Lung Cancer, Gastric Cancer and other advanced Solid Tumors. News release. September 11, 2023. Accessed July 17, 2024. https://www.biosyngen.com/index.php?m=home&c=View&a=index&aid=104