First TCR-T Therapy Nears Market Launch: Overview and Pipeline Updates from 12 Chinese Companies

▲ Progress of 12 TCR-T Companies (Source: EurekaMed organized)

Currently, most companies in the TCR-T space have already entered IIT or clinical trials, with the fastest having advanced to Phase 2 clinical trials.In terms of targets, there are relatively more NY-ESO-1 and viral antigens, but overall, it remains diversified. The types of indications targeted are also quite varied, and it is still a period of healthy competition and innovative development. In the field of solid tumors, there is a trend reminiscent of "the sky is high and the birds can fly freely, the sea is wide and the fish can leap at will," filled with numerous possibilities.

XIANGXUE LIFE SCIENCES

Xiangxue Life Sciences is a research and development enterprise focusing on cell immunotherapy products and technologies in the TCR field. It has established a complete TCR-T product R&D technology system (antigen peptide discovery platform, high-affinity TCR platform, TCR-T development platform) and production preparation system (automated cell production platform, quality control platform).

The company's TCR-T candidate products target a wide range of antigens, including CT antigens, neoantigens, viral antigens, and almost all tumor-specific related antigens. They cover multiple HLA genotypes predominantly found in the Chinese population, such as A0201, A1101, and A2402, with indications spanning various clinically challenging solid tumors.

Currently, GuangDong XIANGXUE LIFE SCIENCES LTD has two products under research approved by the CDE to enter clinical trials.Among them, TAEST16001 is a TCR-T cell therapy product transduced with NY-ESO-1 antigen-specific high-affinity T-cell receptors, used for treating soft tissue sarcoma that is HLA-A*02:01 tissue genotype positive and expresses the tumor antigen NY-ESO-1.This is also the first TCR-T therapy in China to receive an IND approval, and the current Phase 2 clinical research is proceeding smoothly.In February this year, the new indication IND for TAEST16001 has been accepted by the CDE.

In August 2023, the internationally renowned journal Cell Reports Medicine published the Phase 1 clinical research results of TAEST16001:The objective response rate (ORR) was 41.7% among 12 treated patients, with a median progression-free survival (PFS) of 7.2 months, and no treatment-related serious adverse reactions were observed.

In addition, Xiangxue Life Sciences made an appearance at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) held in November 2023, presenting a study in the form of an academic poster: research has proven that a TCR with enhanced affinity and specificity for alpha-fetoprotein (AFP), independently developed by the Xiangxue Life Sciences R&D team, has the potential to overcome tumor antigen escape caused by APM defects. The company has developed a product targeting AFP, TAEST1901, indicated for the treatment of advanced liver cancer or other advanced tumors with a tissue genotype of HLA-A*02:01 and positive expression of the tumor antigen AFP, which is currently in Phase 1 clinical research.

Guangzhou Laien Biological Medicine Co., Ltd.Biology

Guangzhou Laien Biological Medicine Co., Ltd. is committed to exploring, developing, and commercializing first-class, original TCR-T cell therapies for the treatment of viral infections and related cancers. The company has developed complementary mRNA technology platforms and TCR discovery platforms, which utilize mRNA-encoded TCRs. The transient expression characteristics of these TCRs make TCR-T therapy safe and controllable while enabling multiple infusions. Additionally, the company has built the world's largest HBV-specific TCR library, covering 80% of liver cancer patients globally. This library contains a large number of high-affinity, highly specific, and highly expressed TCRs.

The company's first pipeline, LioCyx-M004, can utilize mRNA to encode and express HBV antigen-specific TCR to target liver cancer cells. It was approved by the FDA in September 2021 to carry out a Phase 1b/2 international multicenter clinical study.The phase 1 clinical trial data has preliminarily demonstrated that the product possesses good targeting and sustained anti-tumor effects.

In November 2023, Guangzhou Laien Biological Medicine Co., Ltd. was delighted to receive the 2023 Singapore T-Up Excellence Award at the Singapore Week of Innovation and TeCHnology (SWITCH). In January 2024, Guangzhou Laien Biological Medicine Co., Ltd. signed a strategic cooperation agreement with MaxCyte to launch global collaboration, utilizing mRNA technology to develop TCR-T therapies for solid tumors and virus-related diseases. This cooperation agreement enables Guangzhou Laien Biological Medicine Co., Ltd. to utilize MaxCyte's Flow Electroporation technology.^®Technology and the ExPERT™ platform accelerate the advancement of their clinical programs and commercial applications.

Baiji Biotech

Biotheus is an innovative pharmaceutical company focusing on immune cell therapy with international competitiveness. It has established several proprietary technology platforms for the development and transformation of treatments targeting solid tumors, including M-CEL.^TM、SUPER-T^TM、MSE-T^TM、IDENTIFIER^TM, and has developed CAR-T, TIL, and TCR-T pipelines.

Among them, BRL03 is the world's first fourth-generation TCR-T cell therapy independently developed by Baiji Biologics. It was approved by the CDE to enter clinical trials in January this year for the treatment of various advanced solid tumors, including lung cancer and gastric cancer.In addition, this candidate product was approved by the FDA for Phase 1/2 clinical trials in September 2023. In previous IIT studies, BRL03 demonstrated good safety and preliminary efficacy in the treatment of solid tumors. Notably, the approval of BRL03's IND application in China marks the seventh globally first-in-class product IND clinical approval obtained by Baiji Biotech. Currently, BRL03 is in the Phase 1/2 clinical trial stage.

SCG

SCG is a biotechnology company that develops novel immunotherapies for infectious diseases and related cancers. The core technology of its TCR-T cell therapy platform was developed by Professor Dr. Ulrike Protzer, Director of the Institute of Virology at the Technical University of Munich, Germany, and has been exclusively licensed.

SCG101, developed by SCG, is an autologous hepatitis B virus (HBV)-specific TCR-T cell therapy. Utilizing SCG's proprietary GianTTM technology, it can identify high-affinity and high-specificity natural TCRs targeting intracellular antigens presented by major histocompatibility complex (MHC) in solid tumors. In November 2023, SCG Cell Therapy Pte. Ltd. presented the latest clinical data of this candidate product at the AASLD Liver Meeting:Among 6 patients with advanced HBV-HCC, 2 achieved partial response (PR), 2 had stable disease (SD), and tumor shrinkage was observed.Currently, SCG101 is in the phase 1/2 clinical trial stage.

Tiankeya

Tiankeya, with engineered T cells as the ultimate target, focuses on the innovative research and development and industrialization of tumor immunotherapy cell technologies. Currently, Tiankeya has four centers in Los Angeles and North Carolina in the United States, and Chongqing and Guangzhou in China, with R&D centers and GMP-level manufacturing facilities located in both China and the U.S. Additionally, it has established six major technology platforms.

According to the official website, Tiankeya currently has three TCR-T pipelines, including E202, N201, and L200s, all of which have entered the clinical trial stage. At the 2023 ASCO conference, Tiankeya announced preliminary data from the first-in-human phase 1/2 clinical trial of TCR-T cell therapy secreting immune checkpoint inhibitors for EBV-positive nasopharyngeal carcinoma:As of January 2023, 2 patients (33.3%) had partial responses (PR), with 1 patient experiencing a response duration of up to 9 months, and 3 patients (50%) had stable disease (SD).

In February this year, Tiankeya announced that its Hong Kong company officially moved into the Hong Kong Science Park (HKSTP) to accelerate the global clinical development and commercialization of immune cell therapy. Mr. Su Zhenbo, Chairman of Tiankeya, stated that moving into the Hong Kong Science Park is an important step in Tiankeya's global strategic layout.

Huaxia Yingtai(Beijing)Biotechnology Co., Ltd.

Huaxia Yingtai(Beijing)Biotechnology Co., Ltd. focuses on the development and commercialization of innovative gene-edited T-cell immunotherapy products. Currently, Huaxia Yingtai possesses two innovative T-cell modification platforms, STAR-T and enTCR-T, and has established a rich pipeline of products targeting hematological tumors, solid tumors, and viral infections.

Among them, YTS101 (HXYT-001) is one of the faster-progressing pipelines of Huaxia Yingtai(Beijing)Biotechnology Co., Ltd. It uses synthetic T-cell receptors and antigen receptors (STAR) modified T cells with humanized antibodies targeting CD19 and CD20. The main indication is B-NHL.In its exploratory clinical trial, the ORR of 9 patients reached 100%.Currently, this candidate product is in the phase 1 clinical trial stage.

In November 2023, Huaxia Yingtai(Beijing)Biotechnology Co., Ltd.'s YTS104 IND was accepted by the CDE. YTS104 is an innovative development based on the Synthetic TCR and Antigen Receptor (STAR)-T technology platform jointly developed by Huaxia Yingtai and Tsinghua University. It uses a lentiviral gene transduction method to introduce the STAR gene targeting LILRB4 into autologous T cells. STAR is based on the TCR structure, with its recognition region adopting the specific recognition mechanism of antibodies for tumor target antigens, while integrating the T-cell cascade amplification signaling pathway. This allows it to leverage the high-sensitivity signal transmission advantages of the natural TCR complex to achieve efficient, safe, and long-lasting tumor killing. Additionally, this product utilizes two independently screened nanobodies targeting different epitopes, which are respectively linked to the α and β chains of the STAR structure, and is expected to exhibit better antigen recognition and cytotoxic effects.

Hengrui Yuanzheng

Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. is a biopharmaceutical company that focuses on the development of products related to immunotherapy technologies for solid tumors. Its pipeline includes MASCT products, TCR-T immune cell products, and TCR bispecific antibody products. For TCR-T, Hengrui Yuanzheng has independently developed a TCR screening technology platform based on reverse genetic engineering, which can rapidly and efficiently isolate TCRs with optimal affinity from tumor patients who benefit from immunotherapy, for use in the development of anti-tumor TCR-T products.

HRYZ-T101 is a TCR-T therapy developed by Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. targeting HPV18-related solid tumors such as cervical cancer and head and neck cancer. It exerts its tumor-killing effect by specifically recognizing HLA-antigen complexes on the cell surface and inducing T-cell activation.In October 2023, Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. completed the first TCR-T cell infusion in the Phase 1 clinical trial of HRYZ-T101.

Beijing Kerui Biological Technology Co., Ltd.

Beijing Kerui Biological Technology Co., Ltd. is committed to developing innovative drugs based on TCR. Through technological innovation, it has independently developed the SMART-TCR affinity optimization platform, significantly improving the success rate and efficiency of TCR affinity optimization. This allows for the rapid development of multiple TCR therapeutic products in a short period. Beijing Kerui Biological Technology Co., Ltd. is also advancing both TCR-T cell drugs and TCR protein drugs.

In November 2023, Beijing Kerui Biological Technology Co., Ltd.'s first immunocyte therapeutic product, CRTE7A2-01 TCR-T, was approved for clinical trials.The indication is for HPV16-positive, HLA-A*02:01-positive advanced solid tumors (cervical cancer, head and neck cancer, anal cancer, and other tumor types).

Neowise Biotechnology

Neowise Biotechnology is an innovative company focused on developing TCR-T immunocyte therapeutic drugs for solid tumors, as well as researching clinical technologies and their translation. It has developed an ultra-high sensitivity target-TCR discovery and functional validation platform and established the world's leading target-TCR specificity pairing database, significantly expanding treatment targets and options for patients with solid tumors.

In March 2023, Neowise Biotechnology completed a nearly 200 million yuan A+ round of financing to accelerate the development of TCR-T cell therapy products for solid tumors.In a subsequent interview, Dr. Peng Songming, founder of Neowise Biotechnology, stated, "Within the next 1-2 years, it is expected that 2-4 products in Neowise Biotechnology's R&D pipeline will enter clinical trials." The company’s project titled "Screening of PRAME-targeted TCR and Clinical Application of Related TCR-T Cell Therapy in Various Solid Tumors" was rated as a "Key Project" in the 2023 National Biomedicine Innovation Center for Cell Therapy "Challenge Leader" technology breakthrough initiative. According to official website disclosures, its first PRAME-targeted TCR-T cell therapy pipeline, NW-101, has entered the clinical stage.

Keshihua (Nanjing) Biotechnology Co., Ltd.

Keshihua (Nanjing) Biotechnology Co., Ltd. was founded in 2020 by a team of returned overseas talents from the 2018 Nobel Prize-winning team at the MD Anderson Cancer Center in the United States. The company focuses on the development of HD-TCR T-cell drugs for the treatment of solid tumors, and has established the TCR-XFinder™ sequence discovery platform. Based on accumulated data, it has also built a large tumor-specific T-cell database, TCR-XPlanet™.

HD-TCR (human-derived TCR) Concept Proposed by Keshihua (Nanjing) Biotechnology Co., Ltd.: The Core Idea is to Obtain Potent TCRs from Natural Sequences as Candidate Molecules for Drug Development, Rather than Potent TCR Molecules Obtained Through In Vitro Affinity Optimization. The Advantage of This Strategy Lies in Using TCR Sequences That Have Undergone Negative Selection in the Human Thymus, Which Ensures High Affinity for Antigen Binding While Avoiding Severe Off-Target Toxicity Caused by Artificial Sequence Optimization, Thereby Achieving TCRs with Both Good Safety and Efficacy After Completing POC and Establishing PCC.In January 2024, the IND for KSH01 Injection from Keshihua (Nanjing) Biotechnology Co., Ltd. was accepted, with disclosed indications including various advanced solid tumors.

ImmuXell Biotech

ImmuXell Biotech focuses on the research and production of breakthrough immune cell therapeutic drugs, with its main product being a novel immune cell preparation targeting solid tumors. Currently, ImmuXell Biotech has developed multiple product pipelines with independent intellectual property rights. Among them, the TCR-T cell therapy product targeting KRAS mutations has completed TCR screening, in vitro functional identification, and in vivo efficacy experiments. It has also completed IIT studies for advanced pancreatic ductal adenocarcinoma across multiple clinical centers. According to the company’s official website, this candidate product has entered the IND application preparation stage.

In October 2023, ImmuXell Biotech completed an over 100-million-yuan Series A round of financing. The proceeds will be used to accelerate the application for registration-based clinical trials of a novel TCR-T cell therapy product targeting the KRAS G12V mutation, as well as the development of multiple subsequent innovative pipelines and international collaborations. In December 2023, ImmuXell Biotech announced that it had received the approval notice for the 2023 National Key Research and Development Program's "Frontier Biotechnology" key special project.The immunocyte R&D and application project, in which it participated in the joint application, has been officially approved. This is the first national-level important R&D task undertaken by ImmuXell Biotech.

Liling Biopharmaceutical (Suzhou) Co., Ltd.

Liling Biopharmaceutical (Suzhou) Co., Ltd. focuses on intracellular targets and is committed to the development of personalized TCR-T cell therapies and TCR bispecific antibody drugs. In 2022, Liling Biopharmaceutical completed an angel round of financing worth tens of millions of yuan, which was mainly used for the improvement of the TCR technology platform, the advancement of related project pipelines, and team building.

Last year, according to Dr. Wang Wenbo, founder of Liling Biopharmaceutical (Suzhou) Co., Ltd., in an interview, the company has established a differentiated and advantageous R&D pipeline.The personalized TCR-T therapy for head and neck tumors has completed the proof of concept in vitro and in animal models, and is about to enter the IIT study. This therapy has no target limitations and can achieve multi-targeting.In addition, Liling Biopharmaceutical (Suzhou) Co., Ltd. has developed multiple TCR protein drugs, with indications including cancer and chronic viral infections.

The broad path is not lonely, and the journey with many leads to a distant future. The TCR-T track holds promising prospects.

References:

1.Official Websites and Official WeChat Accounts of Various Companies