On November 14, 2024, Lion TCR, a clinical-stage T-cell immunotherapy company, announced that it has received clearance from the China National Medical Products Administration (NMPA) for its Investigational New Drug (IND) application for GZL-016. This first-in-class product consists of autologous T-cells transfected with mRNA encoding T cell receptors (TCR) specific to the Hepatitis B surface antigen (HBsAg), making this IND approval the world's first for an mRNA-based TCR-T cell therapy targeting HBV in hepatocellular carcinoma.

Liver cancer ranks as the sixth most prevalent cancer globally. In 2022, there were approximately 870,000 new cases and 760,000 deaths, according to the World Health Organization's International Agency for Research on Cancer, with 90% of these cases being hepatocellular carcinoma (HCC). In Asia, the Hepatitis B virus (HBV) significantly contributes to HCC incidence; for instance, in China, 80% to 90% of HCC cases are related to HBV infection. Despite ongoing advancements in liver cancer treatment, effective therapies are still limited, leaving a significant unmet need in patient care. The safety and efficacy of GZL-016 have been evaluated in a Phase 1 study involving primary HBV-related HCC patients. The infusions of GZL-016 were well-tolerated, with no instances of cytokine release syndrome or neurotoxicity reported. The disease control rate was observed at 60%, with a partial response according to RECIST 1.1 criteria lasting an average of 27.7 months. The median overall survival for participants was recorded at 33.1 months.

GZL-016 infusion leverages mRNA technology to encode TCR that specifically target HBV surface antigen. By using electroporation to introduce the HBV TCR gene into T cells, this non-viral method enhances T cells' ability to recognize and eliminate HBV-infected liver and cancer cells, while also improving the safety and controllability of TCR-T cell therapy. Importantly, patients do not need lymphodepletion prior to treatment, allowing for multiple infusions without compromising safety or efficacy.

‍

Notably, GZL-016 has obtained IND approvals from both Singapore's Health Sciences Authority (HSA) and the U.S. Food and Drug Administration (FDA), with the latter granting Fast Track designation in December 2021 due to GZL-016 potential to improve patient survival outcomes in early trials. Currently, GZL-016 is being assessed in an international multicenter Phase Ib/II clinical study.

Dr. Wang Tingting, Chief Medical Officer and Chief Operating Officer of Lion TCR, stated, "Our therapy has demonstrated encouraging clinical results in advanced HCC patients worldwide, including tumor shrinkage, complete disappearance, reduced AFP levels, and extended survival rates. Importantly, no cytokine storms or neurotoxic reactions were observed, confirming the safety and efficacy of our mRNA-encoded TCR-T therapy. We are eager to expand our patient sample size, gather more clinical data, and progress to the next trial phase. Currently, Lion TCR is collaborating with leading cancer specialty hospitals globally to facilitate patient recruitment for multi-site clinical trial, aiming to provide new treatment opportunities for eligible advanced liver cancer patients as soon as possible."

As a pioneer in mRNA-encoded TCR-T cell therapy for solid tumors, Lion TCR is committed to leveraging advanced technologies to deliver innovative treatment options. The company’s mRNA technology platform and AI-driven TCR discovery platform work synergistically to enhance drug development. Dr. Peng Xiaoming, CEO of Lion TCR, emphasized, "We aim to extend our capabilities beyond liver cancer treatment. With these platforms, we can develop mRNA-based therapies targeting various antigens across a broader range of solid tumors. We offer personalized autologous cell therapies as well as accessible 'off-the-shelf' products for both tumor and non-tumor indications." Dr. Peng believes that the integration of mRNA and TCR technology has established a strong foundation for developing 'off-the-shelf' TCR-T products, which the company is actively pursuing.

About Lion TCR

Lion TCR was established in 2015 as a spin-off from A*STAR in Singapore, with the goal of advancing its innovative HBV TCR-T cell therapy, which represents a first-in-class approach. This cutting-edge therapy uses mRNA to encode HBV-specific T cell receptors within patients' T cells, allowing for the targeting of HBV epitopes expressed in liver cancer cells. Clinical trials have shown promising safety and efficacy results. By leveraging its established mRNA technology and TCR discovery platforms, Lion TCR has expanded its range of clinical targets, particularly those related to solid tumors. The company’s expertise enables the delivery of both autologous cell therapies and 'off-the-shelf' solutions. Consequently, Lion TCR is well-positioned to develop a robust pipeline of treatments for various solid cancers and chronic viral diseases, including chronic Hepatitis B, which is closely associated with liver cancer.

‍