EASL Wrap-up: Late-Breaking Data on SCG101 TCR T Cell Therapy Shows Improved Survival in HBV-related Liver Cancer

SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company specializing in novel immunotherapies for infectious diseases and related cancers, has announced groundbreaking clinical data for its innovative treatment, SCG101. This autologous hepatitis B virus (HBV)-specific T-cell receptor-engineered T Cell (TCR T) therapy targets patients with advanced HBV-related hepatocellular carcinoma (HCC).

The clinical data for SCG101 was presented at the European Association for the Study of the Liver (EASL) Congress 2024 held in Milan, Italy. The therapy's dual antiviral and antitumor efficacy was highlighted in a late-breaking session and subsequently included in the Best of EASL Congress Wrap-Up summary, which features the most noteworthy contributions to the program.

The first-in-human clinical trial of SCG101 showcased promising results in patients with advanced HBV-HCC. Six patients received SCG101 at varying doses from 5.0×10^7 to 1.0×10^8 TCR+ T cells per kilogram. The observed objective response rate (ORR) was 33%, with partial responses (PR) maintained for over six months. Notably, one patient achieved complete remission of the target lesion, maintaining progression-free status for 27 months.

The trial also demonstrated a strong correlation between tumor responses and antiviral activities of SCG101. Four out of six patients (67%) experienced significant reductions in serum HBsAg levels by 1-4 log10 after a single infusion of SCG101. These reductions were sustained, with HBsAg levels remaining ≤15 IU/mL for up to 27 months during follow-up. Patients who saw a reduction in serum HBsAg levels of ≥1 log10 exhibited extended median progression-free survival (mPFS: 5.9 vs. 0.7 months) and overall survival (mOS: 19.0 vs. 6.3 months) compared to those without such reductions.

The safety profile of SCG101 was favorable, with no reported cases of serious adverse events (SAE) or immune effector cell-associated neurotoxicity syndrome (ICANS). The most common adverse events related to SCG101 were transient liver enzyme elevations, cytokine release syndrome (CRS), and fever, which were anticipated given the mechanism of the therapy.

Chronic HBV infection is a significant cause of liver cancer, accounting for 50%-80% of HCC cases globally. HBV DNA integration into the host genome leads to genetic instability and abnormal expression of oncogenes, contributing to cancer development. SCG101 targets an HBV peptide presented on HBV-HCC tumor cells and HBV-infected cells, activating cytolytic and non-cytolytic mechanisms to eradicate these cells.

"We are thrilled that our promising data for SCG101 was featured at the EASL Wrap-up session," said Christy Ma, Chief Executive Officer of SCG Cell Therapy. "The data underscores the potential of our GianTCRTM platform to develop effective TCR-based therapies for a range of infectious diseases and associated cancers. We are committed to further exploring SCG101 and other TCR candidates to address unmet medical needs."

SCG101, an investigational TCR T cell therapy, targets a specific epitope of the hepatitis B surface antigen (HBsAg). Utilizing SCG's proprietary GianTTM technology, the therapy identifies high-affinity TCRs against intracellular antigens presented by major histocompatibility complex (MHC) in solid tumors. Preclinical and clinical studies have shown that SCG101 can inhibit tumor growth and eradicate HBV cccDNA. The therapy has received clinical trial approvals from the U.S. FDA, China NMPA, Singapore HSA, and Hong Kong DOH. A Phase 1/2 clinical trial is ongoing (NCT05417932).

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with over 905,000 new cases and more than 830,100 deaths globally in 2020. Chronic HBV infection accounts for a significant proportion of HCC cases, which are often diagnosed at an advanced stage with poor prognosis and a five-year survival rate of less than 15%.

SCG Cell Therapy continues to lead in developing novel immunotherapies for infections and their associated cancers. The company specializes in targeting common cancer-causing infections and has a robust pipeline of TCR-based cellular immunotherapy products. With advanced platforms like GianTCRTM for TCR screening, in-house viral vector production, and AutoCellTM for automated cell therapy manufacturing, SCG is well-positioned to advance cell therapy development from research to clinical application.