Lion TCR's HBV-Targeted TCR-T Therapy LioCyx-M004 Demonstrates Triple Extension in Median Overall Survival for Advanced Liver Cancer Patients; Phase 2 Global Clinical Trial Actively Enrolling

Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer and is associated with a high mortality rate. In China, HBV infection is the main cause of liver cancer, accounting for about 90% of cases.

In recent years, significant progress has been made in the systemic treatment of advanced hepatocellular carcinoma, with targeted therapy combined with immunotherapy gradually becoming the preferred option. Nevertheless, the progression-free survival (PFS) of these combination therapies remains relatively short, ranging from only 4.6 to 6.9 months, limiting their efficacy.Currently, there is no specific treatment method for HBV-related liver cancer available globally., we urgently need more effective treatment methods to meet the actual needs of patients and improve their quality of life.

To this end, from SingaporeLaien BioPioneered the development of the world's first T-cell receptor (TCR-T) therapy, LioCyx-M004, specifically targeting HBV antigens for the treatment of HBV-related advanced adult hepatocellular carcinoma.

T cells, as a component of the human immune system, can act like police to combat foreign pathogens or mutated and aging cells within the body. However, in cancer patients, the immune system is often weakened, leaving T cells unable to recognize or fight effectively. TCR-T cell therapy involves extracting T cells from the patient, engineering them in vitro, and equipping the T cells with TCR.“Weapon”。“Armed”After the T cells are returned to the patient's body, they act like special forces, capable of more precisely identifying cancer cells.“Enemy”, and kill them directly.HBV TCR-T can not only kill cancer cells, but also has the potential to reduce HBsAg levels (hepatitis B surface antigen, one of the clinical indicators for hepatitis virus etiological testing), thereby reducing tumor recurrence rates.

Guangzhou Laien Biological Medicine Co., Ltd.'s HBV TCR-T therapy, as an original First-in-Class cell therapy, has been granted Fast Track designation and Orphan Drug status by the U.S. FDA, fully demonstrating the FDA's high recognition of this therapy.

Recently, we invitedDr. Tingting Wang, Chief Medical Officer and Chief Operating Officer of Guangzhou Laien Biological Medicine Co., Ltd.The "Peak Guest Interview" column under MedPeer, provided us with a detailed analysis of this innovative therapy and its current application progress in the clinical treatment of advanced liver cancer.

According to reports, the HBV TCR-T therapy developed by Guangzhou Laien Biological Medicine Co., Ltd. has previously undergone clinical trial treatments on multiple patients at the Fifth Medical Center of the PLA General Hospital. One patient achieved partial remission (PR) lasting 27.7 months after treatment; three patients had stable disease (SD), which was maintained for up to 9.4 months. The median overall survival (OS) of the patients was 33.1 months.

“Patients with advanced liver cancer typically have a survival period of no more than 1 year. However, after receiving Laien HBV TCR-T treatment, the median overall survival reached 33 months, significantly extending the patients' survival time."Dr. Wang Tingting introduced."

Prolonging overall survival is the gold standard pursued in clinical tumor treatment.Therefore, prolonging overall survival (OS) is the most important indicator for evaluating the efficacy of tumor drug treatments.

Dr. Wang Tingting gave an example:“Even if a drug has a 60% overall response rate, if the median overall survival is only 10 months, its effect may not be as good as a drug with a 30% overall response rate but a median overall survival of 30 months. The latter can help patients achieve longer survival time, essentially transforming the tumor into a "chronic disease" state, which brings greater significance and substantial help to both patients and their families.”

In addition, Dr. Wang Tingting particularly pointed out that in the clinical trials in Singapore, Laien Biological Medicine's HBV TCR-TIt also has a good therapeutic effect on pulmonary metastases of liver cancer, which can significantly reduce the tumor diameter and make the tumor completely disappear.This may be related to the fact that both the lungs and liver have rich vascular networks. Since T cells are transported through the blood to the sites where they function, the therapeutic effects are particularly significant for organs with ample blood supply.

In the treatment of liver cancer, the tumor microenvironment (TME) and tumor heterogeneity are two major obstacles leading to treatment difficulties.

The tumor microenvironment refers to the complex interactions between tumor cells, immune cells, and fibroblasts, which are typically inhibitory to the activity and function of T cells, making it difficult for T cells to exert their tumor-killing effects. Under the influence of this suppressive tumor microenvironment, the reinfused TCR-T cells struggle to maintain long-term tumoricidal activity, as they are quickly inhibited within the TME and unable to effectively perform their anti-cancer functions.This is more prominent in liver cancer, as the liver itself has immunosuppressive properties, which further weaken effective T cell-mediated antigen responses.

Tumor heterogeneity refers to the differences in genotype and phenotype among tumor cells in different patients or in different parts of the tumor within the same patient, even if the tumor occurs in the same location. As a result, tumor cells in the same patient may express different antigens, limiting the drug's efficacy by failing to recognize all tumor cells.

Based on these bottlenecks, Guangzhou Laien Biological Medicine Co., Ltd. has taken an alternative approach, building an mRNA technology platform that applies mRNA-encoded TCR and introduces it into T cells through electroporation.This non-viral vector-dependent, mRNA-mediated transient expression characteristic makes TCR-T therapy safer.Control,Multiple reinfusions can be performed to achieve the desired therapeutic effect. In current clinical trials, patients typically receive intravenous reinfusion once every 1-2 weeks, with 8 times constituting one course of treatment. Notably, the number of cells required for one course of treatment can be obtained from a single blood draw preparation.

Dr. Wang Tingting stated: "Repeated infusions of fresh and potent mRNA-encoded TCR-T cells not only help target attacks on HBV initial antigens but also, through the mechanism of antigen spreading (similar to a chain reaction of immune activation),Enhance T-cell recognition of other tumor-associated antigens, thereby expanding the killing range of T-cells, addressing the challenge of tumor heterogeneity, and providing more comprehensive and lasting anti-cancer effects.Currently, we have already observed the antigen spreading effect induced by HBV TCR-T treatment in liver cancer patients in Singapore."

In addition, Dr. Wang Tingting also mentioned that the flexibility and transience of mRNA technology enable it to respond more quickly to tumor changes, providing dynamic and sustained therapeutic effects. Multiple infusions can continuously supplement and enhance the anti-tumor immune response of TCR-T cells, overcoming the suppressive effects of the TME.

Regarding common side effects in cell therapy, such as neurotoxicity and cytokine release syndrome, Dr. Wang Tingting explained: "This is often due to an overly rapid and intense treatment response. To address this issue, Guangzhou Laien Biological Medicine Co., Ltd. has adopted a 'short-acting, high-quality, multiple-dose' treatment strategy, which involves using transient short-acting TCR-T therapy and dividing the treatment process into eight injections."Each input of cells is like an elite force, capable of efficiently attacking cancer cells. Meanwhile, these cells do not remain in the body for long-term transmission, effectively reducing the occurrence of toxic side effects.”

Clinical trial data from the Fifth Medical Center of the PLA General Hospital and Singapore General Hospital show that Laien Bio's HBV TCR-T therapy has demonstrated good tolerability. During the trial, patients only experienced transient fever and a temporary increase in liver function indicators, with no observed cases of cytokine release syndrome.SymptomAnd neurotoxic side effects.

Moreover, it is worth mentioning that Laien Bio's HBV TCR-T therapy adopts electroporation transfection technology for cell modification. Compared with traditional viral transfection, this method avoids the long-term retention of viral vectors in the body and eliminates the risk of gene insertion, significantly enhancing patient safety.

Clinical Recruitment for Advanced Hepatocellular Carcinoma