Lion TCR Advances mRNA-Encoded TCR-T Cell Therapy Platform with Dual Technology Engines and Global Clinical Progress

In 2022, Dr. Peng Xiaoming, CEO of Lion TCR, led his team to establish the company's China headquarters in Guangzhou's Sino-Singapore Knowledge City. "Guangzhou has abundant hospital resources, and the government provides substantial financial and policy support to pharmaceutical companies. We see great potential in Guangzhou’s pharmaceutical industry, so we decided to locate our China headquarters here, which will be an integrated base for R&D, clinical trials, and GMP production," said Peng Xiaoming.

Before landing in China,Guangzhou Laien Biological Medicine Co., Ltd. was incubated from A*STAR (Agency for Science, Technology and Research) in 2015.Focusing on the internationally leading First-in-Class HBV TCR-T therapy, and applying it in clinical trials for liver cancer treatment through mRNA technology encoding TCR, demonstrating good safety and significant efficacy. Currently,Guangzhou Laien Biological Medicine Co., Ltd. has established an mRNA technology platform and a TCR discovery platform.Expanding targets and different indications for solid tumors, while simultaneously developing autologous cell therapy and off-the-shelf therapy product platforms to provide innovative solutions for unresolved clinical issues. This includes ongoing and planned initiatives for liver cancer and chronic hepatitis B, with the potential to expand to other solid tumor indications in the future.

Laien Bio's forward-looking technology and product layout have garnered attention and recognition within the industry, earning it consecutive industry awards this year. On May 5th to May 7th, during the 7th Future Healthcare 100 Summit hosted by VCBeat, Laien Bio was honored with the Pengcheng Award for Annual Potential Enterprise. This award evaluates companies based on their annual value growth and innovative breakthrough performance, aiming to recognize enterprises that focus on innovation in business models, scientific research, technology, and product development while striving for breakthroughs. With numerous candidates vying for the award, Laien Bio stood out.

Dr. Peng Xiaoming (left), CEO of Guangzhou Laien Biological Medicine Co., Ltd., and Dr. Wang Tingting (right), Chief Medical Officer and Chief Operating Officer

When Guangzhou Laien Biological Medicine Co., Ltd. was founded, it adhered to the combination of mRNA technology and TCR-T cell technology. However, in the early stages of development, Laien faced significant pressure. Almost everyone in the industry used lentiviral transfection of T cells, while Laien was the only cell therapy company in the market that insisted on using non-viral transfection technology encoded by mRNA. What made Peng Xiaoming feel relieved was that with the approval of the mRNA vaccine for COVID-19 prevention, this affirmed the drug-like properties of mRNA and also provided an opportunity for more upstream raw material companies focusing on mRNA synthesis to develop rapidly. Not only could the production cost of mRNA be significantly reduced, but therapeutic technologies based on mRNA would also be greatly expanded. Currently, an increasing number of companies have begun to realize the advantages of mRNA and enter this field.

To date, Laien has built two major technology platforms: the mRNA technology platform and the TCR discovery platform, which complement each other, further pushing the ceiling for Laien's new drug research and development.

Currently, CAR-T cell therapy using viral vector transduction of T cells has achieved certain efficacy in hematological tumors. However, 90% of tumors are solid tumors. "The inherent tumor heterogeneity and complex tumor microenvironment of solid tumors can cleverly help them resist or escape various treatments. Overcoming solid tumors is a significant challenge. CAR-T strategies that have proven effective in hematological tumors may not work for solid tumors. For example, in CAR-T treatment, the expansion and long-term persistence of T cells in the body are usually pursued. But in fact, the expansion of CAR-T in solid tumors is limited. Even if there is expansion, these T cells may be hidden in the tumor site, where their function is suppressed by the tumor immune microenvironment, leading to T cell exhaustion and loss of cytotoxic function. You cannot hope to cure solid tumors with just one infusion," introduced Peng Xiaoming.

In addition to the unique challenges posed by solid tumors, preparation and production also present significant hurdles. Currently, transfection using viral vectors is very costly, making multiple infusions difficult to achieve. Moreover, viral vectors can persist in the body for a long time and are not suitable for repeated dosing.

It is precisely based on these bottlenecks that Guangzhou Laien Biological Medicine Co., Ltd. has taken an alternative approach by building an mRNA technology platform, applying mRNA-encoded TCR and introducing it into T cells. The transient expression characteristics of mRNA make TCR-T therapy safe and controllable, and also allow for multiple administrations. Each infusion of fresh and potent TCR-T cells can quickly initiate an attack on tumor cells., which can overcome the inhibitory effect of the tumor immune microenvironment to a certain extent. In the future, there will be more opportunities to move the treatment plan forward to early-stage tumors, or even prevent tumors.

Another technology platform that Laien Bio has been building and iterating is the TCR discovery platform.Currently, through continuous sample accumulation, Guangzhou Laien Biological Medicine Co., Ltd. has built the world's largest HBV-specific TCR library, which can cover 80% of liver cancer patients globally. The library contains a large number of TCRs with affinity, specificity, and high expression.Guangzhou Laien Biological Medicine Co., Ltd.'s first-generation TCR discovery platform is biology-based, leveraging a significant number of patient samples. Building on this foundation, the company can explore various viral targets and even tumor targets. In this process, Laien has also integrated AI technology to assist in upgrading the TCR discovery platform, aiming to accumulate richer data sources and improve the efficiency of TCR and target discovery.

Based on this platform technology design concept, Guangzhou Laien Biological Medicine Co., Ltd. designed and modified the first-generation TCR-T drug in vitro. This is an autologous cell therapy that uses mRNA technology to encode HBV-specific TCR into T cells for the engineering modification of T cells.

In Peng Xiaoming's view, the combination of mRNA and TCR technology will also lay a technical foundation for in vivo TCR therapy. The company is actively making arrangements in this area and has gained recognition from leading pharmaceutical enterprises.

The mRNA technology platform and TCR discovery platform developed by Laien are, in fact, a dual-driver system that jointly raises the ceiling for Laien's innovative drug development. Peng Xiaoming stated: "We aim to prove that our company can do more than treat liver cancer. By leveraging these technology platforms, Laien can develop mRNA-based therapies targeting different antigens and cover a broader range of disease areas. At the same time, we can provide not only autologous personalized cell therapy but also off-the-shelf products and clinical solutions, such as for early- to mid-stage liver cancer and chronic hepatitis B, with the potential to expand into cancer prevention and other solid tumor indications."

Although Guangzhou Laien Biological Medicine Co., Ltd. was founded in Singapore, it has long established close ties with China.

Professor Antonio Bertoletti, as the scientific founder of the company, has accumulated more than 30 years of research experience in the field of hepatitis B virus.He also began exploring TCR-T therapy at an early stage, serving as a scientific advisor for renowned pharmaceutical companies such as Gilead, Janssen, MedImmune, and Vir Biotechnology. He also worked at A*STAR, researching the HBV virus and TCR-T therapy. During the early exploratory phase of Laien from 2015 to 2019, Professor Antonio Bertoletti, together with Academician Wang Fusheng from the Fifth Medical Center of the Chinese People's Liberation Army General Hospital, conducted IIT clinical trials and obtained preliminary clinical data. This is how Laien formed its ties with China.

Peng Xiaoming, who has been accompanying Laien's growth, has worked at A*STAR for over 15 years and has more than 20 years of experience leading Ph.D. research teams, as well as project management and financing experience in AI-related fields.He is very optimistic about the combination of AI and biotechnology, especially the therapeutic potential and development prospects of using cellular immunotherapy to conquer tumors. He recognizes the underlying logic of Laien’s use of mRNA technology combined with TCR-T cell therapy for treating solid tumors. In 2020, Peng Xiaoming was invited to become the CEO of Guangzhou Laien Biological Medicine Co., Ltd., personally participating in planning Laien's future development strategy and pushing the company towards a more professional and comprehensive path. During the same period, the company attracted a group of senior talents deeply rooted in the industry, including Chief Medical Officer and Chief Operating Officer Dr. Wang Tingting. The company now has an integrated team covering all aspects, including R&D, clinical, quality management, and GMP production.

With the support of a strong technical foundation, cutting-edge technology platforms, and an experienced talent team, Guangzhou Laien Biological Medicine Co., Ltd. has embarked on a path of differentiation.In terms of TCR discovery, Guangzhou Laien Biological Medicine Co., Ltd. selects naturally occurring TCRs and, through necessary modifications, ensures a higher level of safety. In terms of target selection, the company has chosen the hepatitis B virus as the target, which not only better avoids issues related to tumor heterogeneity but also guarantees the effectiveness of TCR-T therapy in treating solid tumors.

The company's comprehensive development has given Laien more opportunities to strengthen close ties with China. After obtaining the Phase Ib/II IND clinical approval from the U.S. FDA, Laien decided to continue building its industrial development in China, establishing a GMP facility in Guangzhou, China.

In the future, Laien will continue to advance the international clinical trials of LioCyx-M004, leveraging the FDA's Fast Track designation granted to Laien to accelerate the release of Ib/II phase IND clinical data.At the same time, it will also accelerate the upgrading of the technology platform, and based on this, expand and layout the indications and product pipelines. Laien will continue to focus on innovative technologies to address current unmet clinical needs, reward shareholders, and safeguard human life and health.