SCG Cell Therapy Unveils Promising Phase 1 Data for HBV TCR-T Therapy at 2024 AASLD Meeting

SCG Cell Therapy Pte Ltd (SCG), a biotechnology firm at the clinical trial stage, is pioneering innovative immunotherapies targeting infectious diseases and related cancers. The company recently unveiled promising data from its Phase 1 trial of SCG101, an advanced T-cell receptor-engineered T Cell (TCR-T) therapy designed to combat hepatitis B virus (HBV). This groundbreaking therapy aims at reducing hepatitis B surface antigen (HBsAg), providing hope for patients with advanced HBV-related hepatocellular carcinoma (HBV-HCC). The findings were shared at the 2024 AASLD Liver Meeting in San Diego, USA.

In the Phase 1 trial, SCG101 demonstrated notable antiviral efficacy in patients suffering from advanced HBV-HCC. The study involved 12 patients who received a single intravenous dose of SCG101 ranging from 5.0×10^7 to 1.0×10^8 TCR+ T cells/kg. Remarkably, all participants showed a significant decrease in serum HBsAg levels. Specifically, 92% of the patients experienced a reduction ranging from 1.0 to 4.6 log10, with HBsAg levels staying below 100 IU/mL over a follow-up period of up to one year. Impressively, four patients achieved complete HBsAg loss within 21 days post-infusion, and this loss was sustained throughout the monitoring period.

The safety profile of SCG101 was generally positive, with the treatment being well-tolerated by the patients. The most frequently observed treatment-related side effects included temporary increases in liver enzymes, fever, low blood cell counts, cytokine release syndrome (CRS), low albumin levels, and low sodium levels. These side effects are consistent with the therapy’s action mechanism, which involves immune activation targeting HBsAg and the subsequent clearance of infected liver cells and cancerous cells.

HBV continues to pose a significant global health challenge, impacting over 250 million individuals worldwide and being a leading cause of liver cancer. Chronic HBV infection is a primary factor in the development of hepatocellular carcinoma, accounting for 50%-80% of cases. The persistent expression of HBsAg, due to HBV DNA integration into the host genome, contributes to chromosomal instability and oncogene activation, resulting in cancer progression.

SCG101 is designed to target a specific peptide of HBV presented on infected cells and liver cells with integrated HBV DNA. It activates both cytolytic and non-cytolytic mechanisms to efficiently eliminate HBV-infected hepatocytes as well as precancerous and HBV-HCC cells with integrated HBV DNA.

Christy Ma, SCG Cell Therapy's Chief Executive Officer, emphasized the significance of the trial's positive outcomes, highlighting the therapy’s potential to offer meaningful and enduring antiviral responses for patients. She stated that these findings validate the novel approach employed in developing HBV-specific TCR T cell therapy. Ma expressed the company’s commitment to advancing SCG101 through further clinical development, aiming to provide a new therapeutic option for patients grappling with this challenging disease. She also mentioned the potential of the GianTTM TCR discovery platform to address a wide range of infection-associated cancers, such as those related to human papillomavirus (HPV) and Epstein-Barr virus (EBV), thereby heralding a new era in immune-based cancer treatments.

SCG101 is an investigational autologous TCR T cell therapy targeting a specific epitope of HBsAg. Utilizing SCG’s proprietary GianTTM technology, their TCR screening platform identifies high-affinity natural TCRs against intracellular antigens presented by the major histocompatibility complex (MHC) in solid tumors. Both preclinical and clinical trials have shown significant tumor inhibition and the elimination of HBV covalently closed circular DNA (cccDNA). SCG101 has received clinical trial approvals from several health authorities, including the U.S. FDA, China NMPA, Singapore HSA, and Hong Kong DOH, for treating patients with HBV-related HCC. A Phase 1/2 clinical trial of SCG101 is currently in progress.