Lion TCR's Liocyx-M004 Receives FDA Clearance to Launch Global Multicenter Phase 2 Clinical Trial in HBV-Related Hepatocellular Carcinoma

SINGAPORE, Feb. 12, 2025 /PRNewswire/ -- On 12 Feb 2025, Lion TCR announced that its mRNA-encoded T-cell receptor (TCR)-T cell therapy product Liocyx-M004 has received clearance from the U.S. Food and Drug Administration (FDA) to initiate an international multicenter Phase 2 clinical trial. This significant progress further solidifies Lion TCR's leading position in the mRNA-based TCR-T field and brings new hope to patients with hepatocellular carcinoma (HCC).

Hepatitis B and liver cancer are significant global public health challenges. Hepatitis B virus (HBV) infection is a leading risk factor for liver cancer, particularly HCC. Globally, an estimated 296 million people live with chronic HBV infection. Liver cancer is the sixth most common cancer worldwide. In 2020 alone, there were approximately 905,000 new cases and 830,000 deaths from liver cancer globally. Liocyx-M004 is the world's first mRNA-encoded TCR-T cell therapy targeting HBV-related hepatocellular carcinoma. The FDA-approved international multicenter Phase 2 clinical trial will evaluate the efficacy of Liocyx-M004 as a monotherapy and in combination with lenvatinib. Lenvatinib, a well-established first-line treatment for advanced hepatocellular carcinoma, demonstrates the ability to reprogram the immunosuppressive tumour microenvironment into an immune-supportive state, thereby enhancing tumour-killing efficacy. When combined with Liocyx-M004, this therapy is anticipated to create synergistic effects, further amplifying its anti-tumour potential and improving patient outcomes.

Dr. Tina Wang, Chief Medical Officer and Chief Operating Officer of Lion TCR, explained: "In patients with HBV-related hepatocellular carcinoma, HBV-specific T cells are often functionally exhausted, leading to a significant impairment in their ability to eliminate liver cancer cells and HBV-infected liver cells with HBV-DNA integration. Our research has shown that HBV-specific TCR-T cells can effectively target and destroy these cancerous cells. This makes the adoptive transfer and supplementation of autologous HBV-specific TCR-T cells a promising therapeutic strategy, with the potential to restore the HBV-specific T cell pool in patients. This approach enables targeted killing of liver cancer cells and infected liver cells expressing HBV antigens, providing a novel treatment option for HBV-related hepatocellular carcinoma. While systemic therapies for advanced hepatocellular carcinoma have made significant strides in recent years, including the development of targeted combination immunotherapies, precision treatments for HBV-related hepatocellular carcinoma remain limited. By investigating the combination of Liocyx-M004 with lenvatinib, we aim to further improve response rates and survival outcomes for these patients. The FDA's approval of this international multicenter Phase 2 clinical trial is a major milestone that strengthens our confidence and commitment to advancing mRNA-encoded TCR-T therapies for hepatocellular carcinoma. Moving forward, we will accelerate the trial's progress and gather clinical data to bring this innovative treatment to patients as soon as possible."

Dr. Xiaoming Peng, CEO of Lion TCR, remarked: "Liocyx-M004 is the first TCR-T therapy targeting HBV viral antigens to receive IND approval from the U.S. FDA and the first of its kind to be granted Fast Track designation. This approval for Liocyx-M004 to proceed with international multicenter Phase 2 clinical trials underscores its significance as an innovative therapy for liver cancer and represents a major milestone for Lion TCR. It also signifies a critical step in Lion TCR's transition from the clinical stage to commercialization. While advancing our lead product through these critical trials, we are simultaneously accelerating the development of an 'off-the-shelf' (or 'universal') in vivo TCR-T product platform, leveraging mRNA-LNP delivery technology to significantly reduce production costs. In parallel, we are enhancing our AI-powered TCR discovery platform to expand our pipeline into treatments for various solid tumors with high unmet needs, including lung cancer, breast cancer, and gastrointestinal cancers."

Liocyx-M004 has already demonstrated promising outcomes in earlier clinical trials, achieving a median overall survival of 33.1 months in patients with HBV-related hepatocellular carcinoma.

About Lion TCR

Lion TCR is a clinical-stage biotechnology company, originally spun off from Singapore's Agency for Science, Technology and Research (A*STAR), and a pioneer in mRNA-encoded TCR-T cell therapies for the treatment of solid tumors and infectious diseases. Its flagship product, Liocyx-M004, is the world's first FDA-approved TCR-T cell therapy targeting HBV-related hepatocellular carcinoma (HCC) to enter international multicenter Phase 2 clinical trials. The therapy has also been granted FDA Fast Track and Orphan Drug designations. In November 2024, Lion TCR achieved another milestone with IND approval from China's National Medical Products Administration (NMPA), marking significant progress in advancing TCR-T cell therapy.

By leveraging cutting-edge mRNA technology and an AI-driven TCR discovery platform, Lion TCR is expanding its pipeline to target various solid tumors and infectious diseases, including lung cancer, breast cancer, and gastrointestinal cancer. The company is also developing both autologous cell therapies and 'off-the-shelf' therapies using mRNA-LNP delivery technology to significantly reduce production costs while ensuring scalability in manufacturing.

Lion TCR has successfully raised over 300 million yuan in funding, led by Guangzhou Industrial Investment Fund, alongside Guangzhou Guoju Investment Fund (a private equity subsidiary of Guangzhou Hi-Tech Investment Group Co., Ltd.) and CSPC NARD Capital Fund. The company has established its China headquarters in Guangzhou Sino-Singapore Knowledge City and is constructing a GMP-compliant innovative drug facility. This facility complements its GMP base in Singapore, creating a comprehensive global platform that integrates research, clinical operations, and production. Through its China-Singapore collaboration, Lion TCR aims to establish itself as a global leader in mRNA-encoded TCR-T cell therapies.