#Singapore #SCG101 #SCG Cell Therapy #TCR-T Therapy

SCG Cell Therapy's SCG101: A Promising New Hope for Hepatitis B Patients

SCG Cell Therapy Pte Ltd, a Singapore-based biotechnology firm dedicated to creating innovative immunotherapies for infectious diseases and related cancers, has unveiled compelling results from its Phase 1 clinical trial of SCG101, a first-of-its-kind autologous T-cell receptor-engineered T Cell (TCR-T) therapy that specifically targets the hepatitis B virus (HBV). This significant data was disclosed at the prestigious AASLD Liver Meeting 2024, held in San Diego, California.

In recent findings from the study, SCG101 has demonstrated remarkable antiviral effectiveness in patients diagnosed with advanced HBV-related hepatocellular carcinoma (HBV-HCC). Out of 12 participants who received a single intravenous dose ranging from 5.0×10^7 to 1.0×10^8 TCR+ T cells per kilogram, every patient exhibited a notable decrease in serum HBsAg levels. A staggering 92% of patients (11 out of 12) experienced a reduction ranging from 1.0 to 4.6 log10, maintaining HBsAg levels below 100 IU/mL for up to a year during follow-up. Furthermore, among these patients, four individuals, accounting for 33%, achieved complete HBsAg loss within just 21 days post-infusion, a milestone that persisted throughout the follow-up period.

The safety profile associated with SCG101 has also been favorable, revealing that the treatment is generally well-tolerated. Among the most common treatment-related adverse events documented were transient liver enzyme elevations, fever, cytopenia, cytokine release syndrome (CRS), hypoalbuminemia, and hyponatremia. These were in line with the therapy's mechanism, which triggers immune activation aimed at the HBsAg and mediates the clearance of diseased liver cells and associated cancer cells.

Hepatitis B virus remains a serious global health challenge, affecting over 250 million individuals worldwide and standing as a primary contributor to liver cancer, responsible for 50-80% of all hepatocellular carcinoma cases globally. Persistent HBV infection can lead to HBV DNA's integration into the host genome, which results in continuous HBsAg expression, chromosomal instability, and the activation of oncogenes, ultimately fostering the development of hepatocellular carcinoma. SCG101 is engineered to target a specific HBV peptide found on infected cells, as well as hepatocytes where HBV DNA has integrated, allowing it to trigger both cytotoxic and non-cytotoxic responses that effectively eliminate HBV-infected liver cells and those that are precursors to HBV-HCC.

Christy Ma, CEO of SCG Cell Therapy, expressed optimism regarding these promising Phase 1 trial results, stating, "The positive outcomes from our clinical trial signify a crucial step forward for SCG101, our pioneering HBV-specific TCR-T therapy. Not only do these results illuminate SCG101's potential in achieving significant and durable antiviral responses, but they also highlight our unique approach in the realm of HBV-specific TCR therapies. We are excited by these initial findings and are dedicated to propelling SCG101 through subsequent phases of clinical development in our aim to provide a new therapeutic option for those afflicted by this complex disease."

Furthermore, Ma noted the potential of SCG’s GianTTM TCR discovery platform to tackle a wide range of cancers linked to infections, including those associated with human papillomavirus (HPV) for cervical and head and neck cancers, and Epstein-Barr virus (EBV) concerning nasopharyngeal and gastric cancers. This could pave the way for a significant shift in immune-based cancer treatment paradigms.

The Mechanism and Future of SCG101

SCG101 is characterized as an investigational autologous TCR-T cell therapy targeting a unique epitope of the hepatitis B surface antigen (HBsAg). Utilizing SCG's proprietary GianTTM technology, the TCR screening platform identifies high-affinity, high-avidity natural TCRs against intracellular antigens presented via the major histocompatibility complex (MHC) of solid tumors. Both preclinical and clinical trials involving SCG101 have showcased its capacity to significantly inhibit tumor growth and eradicate the covalently closed circular DNA (cccDNA) linked to HBV. This therapy has garnered approvals for clinical trials from regulatory bodies, including the U.S. FDA, the China National Medical Products Administration (NMPA), Singapore's Health Sciences Authority (HSA), and Hong Kong's Department of Health (DOH), specifically for treating patients with HBV-related hepatocellular carcinoma.

Understanding Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents the most prevalent form of liver cancer. Recent estimates revealed over 905,000 new cases diagnosed globally in 2020, with more than 830,100 deaths attributed to liver cancer. Chronic HBV infection accounts for at least 50% of HCC occurrences worldwide. Unfortunately, HCC tends to be diagnosed at advanced stages, often resulting in a dismal prognosis with a five-year survival rate falling below 15%.

In summary, SCG101 emerges as a beacon of hope for patients battling hepatitis B-related liver cancer. With its unique approach and robust early data, SCG Cell Therapy is poised to redefine therapeutic options available to those impacted by this devastating disease.