SINGAPORE, Nov. 14, 2023 /PRNewswire/ -- SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, today announced late-breaking clinical data from its first-in-class autologous hepatitis B virus (HBV)-specific T-cell receptor-engineered T Cell (TCR-T) therapy – SCG101 – at the 2023 AASLD Liver Meeting in Boston, United States.

Results from a first-in-human clinical trial showed that SCG101 demonstrated promising antiviral and antitumor activities in patients with advanced HBV-related hepatocellular carcinoma (HCC). In six patients with advanced HBV-HCC who received a single IV dose of SCG101 at 5.0×10⁷ ~ 1.0×10⁸ TCR+ T cells/kg, 2 out of 6 (33%) patients achieved partial responses (PR) and 2 of 6 patients had stable diseases (SD) with tumor reduction observed.

The tumor responses were highly correlated with the antiviral activities of SCG101. As of the data cutoff, 6 out 6 (100%) patients experienced serum HBsAg reduction and 4 out of 6 (67%) achieved reduction of 1~3 log after SCG101 infusion. The HBsAg level maintained ≤20 IU/mL throughout the follow up period for up to 90 weeks. Tumor reduction was observed in all 4 patients with serum HBsAg reduction >1 log, and the median progression free survival (PFS) was prolonged (25.8 versus 3.1 weeks) in patients with HBsAg reduction >1 log than in those without.

The safety analysis revealed that SCG101 was generally well tolerated with no cases of serious adverse events or immune effector cell-associated neurotoxicity syndrome. The most common treatment-related adverse events were transient liver enzymes evaluation, cytokine release syndrome (CRS), and fever, which were expected due to SCG101's mechanism of diseased hepatocytes clearance and immune activation.

HBV infection is a leading cause of liver cancer and accounts for 50%-80% of hepatocellular carcinoma cases worldwide.^[1] HBV DNA integrates into the host genome and leads to genetic instability of the host cell and epigenetic remodelling of host DNA, resulting in abnormal expression of oncogenes and HBV antigens.^[2] SCG101 can specifically target an HBV peptide presented on HBV-HCC tumor cells, HBV-DNA integrated premalignant hepatocytes, and HBV-infected cells, triggering cytolytic and non-cytolytic mechanisms to eliminate tumor cells and HBV-infected cells.

"We are excited to be the first to demonstrate the potential of HBV TCR T cell therapy to achieve promising tumor responses in solid tumors and induce durable antiviral activities. This unique dual function of SCG101 offers a new approach to treating HBV-associated HCC by targeting the underlying cause of cancer", said Frank Wang, Chief Executive Officer of SCG Cell Therapy. "We believe our GianT^TM TCR discovery platform has the potential to tackle a wide range of infection-associated cancers, such as Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), and ultimately establish a new paradigm in immune cancer treatment".

About SCG101

SCG101, an autologous T-cell receptor (TCR) T cell therapy, is an investigational cell therapy product targeting a specific epitope of hepatitis B surface antigen (HBsAg). Utilizing SCG's proprietary GianT^TM technology, high affinity and high avidity natural TCRs can be identified against intracellular antigens presented through major histocompatibility complex (MHC) in solid tumours. Preclinical and clinical studies of SCG101 demonstrated tumour inhibition and HBV cccDNA eradication. SCG101 was granted clinical trial approvals by the U.S Food and Drug Administration (FDA), China National Medical Products Administration (NMPA) and Singapore Health Science Authority (HSA) and Hong Kong Department of Health (DOH) for patients with HBV-related HCC. A Phase 1/2 clinical trial evaluating SCG101 is ongoing (NCT05417932).

About Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It is estimated that more than 905,000 new cases of liver cancer and more than 830,100 deaths from the disease globally in 2020, making it one of the leading causes of cancer deaths around the world.^[3] Chronic HBV infection accounts for at least 50% of cases of HCC worldwide.^[1] HCC is typically diagnosed at an advanced stage and is associated with a poor prognosis. The five-year survival rate of less than 15%.^[4]  

About SCG Cell Therapy

SCG is a leading biotechnology company focusing on the development of novel immunotherapies in infections and its associated cancers. The company targets the most common cancer-causing infections: helicobacter pylori, HPV, HBV and EBV, and develops a broad and unique pipeline of T cell therapies, antibodies, and therapeutic vaccines against infections to prevent and cure its associated cancers. Established and headquartered in Singapore, SCG combines regional advantages in Singapore, China and Germany, covering the entire value chain from innovative drug research and discovery, manufacturing, clinical development and commercialization. For more information about SCG, please visit us at www.scgcell.com.

[1] Y, Xie. (2017). Hepatitis B virus-associated hepatocellular carcinoma. Advances in experimental medicine and biology.

[2] Jiang, Y., Han, Q., Zhao, H., Zhang, J. (2021, May 20). The mechanisms of HBV-induced hepatocellular carcinoma. Journal of hepatocellular carcinoma.

[3] Liver cancer statistics: World cancer research fund international. WCRF International. (2022, April 14).

[4] Golabi P, Fazel S, Otgonsuren M, Sayiner M, Locklear CT, Younossi ZM. (2017). Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities.

Source: SCG