Introduction: In recent years, with the steady progress in biomedical technology, there have been significant breakthroughs in cell therapies, particularly in immunotherapy and stem cell therapy, capturing considerable public attention. Among these, CAR-T immunotherapy has emerged as a leading trend in cancer treatment, gaining prominence as a breakthrough approach.

CAR-T cell therapy has emerged as a key treatment option for patients with relapsed or refractory hematological cancers. Currently, within China, six CAR-T therapies have been approved for market use.

In July this year, Chongqing Precision Biotech announced that China National Medical Products Administration (NMPA) has formally accepted the New Drug Application for its National Class I biological new drug pCAR-19B cell autologous infusion preparation (Puzolcabtagene Autoleucel Injection), China’s first CAR-T product for the treatment of CD19 positive relapsed/refractory acute lymphoblastic leukemia (ALL) patients aged from 3 to 21 years old. Notably, this therapy was developed by Precision Biotech over a 7-year period and is expected to receive approval within the next year.

Within Precision Biotech’s pipeline, multiple cell therapy candidates for various indications are in registrational clinical trials, featuring high target specificity.

On this occasion, the "Fengke Interview" column of eMedClub specially invited Professor Qian Cheng, Chairman and Chief Scientist of Precision Biotech, to give us an interview to share  Precision Biotech’s latest progress, innovations and pipeline strategies in the CAR-T field as well as the future development trend of the industry.

Professor Qian Cheng

As the chairman and chief scientist of Chongqing Precision Biotech Co., Ltd., Professor Qian Cheng has been selected into the list of "Elsevier Highly Cited Chinese Researchers" for many  years. He is the Director of National International Joint Research Center for Precision Medical Biotherapy of Ministry of Science and Technology of China and Chief Scientist of the Key Research and Development Program of the Ministry of Science and Technology of China. With 30 years of experience in cancer research, including basic, translational, and clinical trials, Professor Qian has published over 200 papers and filed over 80 PCT and national patents. In 2016, he led the establishment of Chongqing Precision Biotech, establishing a comprehensive industry chain encompassing independent R&D, production, and testing. The company has applied for more than 150 invention patents for core key technologies, laid out more than 10 R&D pipelines including immune cells and stem cells, and obtained the implied license of 4 CAR-T cells Class I new biological drug and 9 indications.

Fengke reporter: As a veteran expert in precision oncology, you hold prestigious roles such as Chief Scientist for national key R&D programs and Director of the Tumor Precision Medicine Research Center. Your extensive background in cancer research spans basic, translational, and clinical trials. So, from a clinician to the founder of Precision Biotech, what prompted you to choose the field of cell therapy? What unique advantages did your past clinical experience bring to your exploration in this field?

Professor Qian Cheng: As one of the pioneering researchers in cell and gene therapy (CGT) and cancer research worldwide, I have devoted my entire career to understanding and treating cancer from multiple angles. I have always been committed to applying my knowledge into practical cancer cures. My extensive research experience has deepened my understanding of cancer, particularly in the realm of CGT, and has given me a clear insight into the future direction of CGT. Additionally, my close interactions with cancer patients have allowed me to grasp their urgent needs more effectively. These patient needs and clinical requirements significantly guide and support our strategic decisions in product development.

Faced with the challenges of tumor treatment, such as the high risk of recurrence and metastasis, the limited effectiveness of immunotherapy for solid tumors, and the prohibitive cost, Chongqing Precision Biotech has developed several key technological platforms. These include the PsionCAR platform, characterized by its humanized and fully human structures with high efficacy, the PrimCAR platform offering high safety and sustained effects, the UCAR-T and CAR-NK platforms known for their convenience, speed, and uniformity, the HyeCAR platform capable of multi-antigen recognition to prevent recurrence through dual/multi-targeting, the PhiCAR platform designed to penetrate the tumor’s physical microenvironment, the ResCAR platform targeting the tumor immune microenvironment, and the VivoCAR for generating CAR-T cells in vivo. The advancements in these technologies parallel the development of our new drugs, leading to the creation of innovative pharmaceutical products that exceed patient expectations and withstand market scrutiny.

Fengke reporter: In July this year, Chongqing Precision Biotech announced that NMPA has formally accepted the New Drug Application for its National Class I biological new drug Puzolcabtagene Autoleucel Injection. We know that the IIT study for this project started around 2017, during a period when the domestic cell therapy industry was experiencing a downturn. Additionally, this product has distinct indications compared to the same target CAR-T drugs already on the market. Could you please share what forward-looking considerations and judgments led Precision Biotech to make such an early strategic move?

Professor Qian Cheng: Innovation is crucial in scientific research, and the development of new drugs must avoid homogeneous competition, we need to rely on technological leadership and the courage to be one step ahead. As one of the earliest teams to carry out CAR-T basic and clinical research in China, we have extensively explored various indications and accumulated substantial clinical experience. Pediatric acute lymphoblastic leukemia (ALL) has a higher incidence rate, and at the same time, there is a greater expectation for the safety of treatment. In the early stages of the industry’s development, both international and domestic counterparts primarily targeted the adult population. However, we chose to challenge and address the treatment needs of pediatric ALL patients.

This year, NMPA has formally accepted the New Drug Application for our National Class I biological new drug Puzolcabtagene Autoleucel Injection which was also included in the priority review. This is the first CAR-T drug for childhood leukemia in China and the first product of Precision Biotech to be approved for marketing. Over the past eight years, we have tirelessly refined and enhanced every aspect of the product, from its overall design to the smallest details, aiming to improve its efficacy. This ongoing process reflects our commitment to addressing the health issues faced by patients and the challenges in tumor treatment through our research and development efforts.

Fengke reporter:The CD19 target is a significant and extensively researched focus in the treatment of B-cell lymphoma and B-cell acute lymphoblastic leukemia (B-ALL). We’ve learned that your company is also conducting clinical trials of this candidate product in adult patients. In such a fiercely competitive market, how do you evaluate the core advantages of Puzolcabtagene Autoleucel Injection?

Professor Qian Cheng: Regarding product development, Puzolcabtagene Autoleucel Injection is the first CAR-T product developed using humanized CD19 antibodies among the same target CAR-T products applied in China. During its humanization process, we gave special consideration to the HLA typing characteristics of the Chinese population, securing numerous patents both internationally and domestically.

Based on the clinical data collected, Puzolcabtagene Autoleucel Injection has demonstrated a strong and sustained presence in vivo. In the phase I clinical trial for treating pediatric acute lymphoblastic leukemia, all nine patients enrolled achieved complete remission (CR), resulting in an overall response rate of 100%. The phase II clinical data have been submitted for presentation at this year’s ASH conference, where full details will be revealed.

In the crowded CD19 target CAR-T field, Precision Biotech's Puzolcabtagene Autoleucel Injection is the first CAR-T treatment product in China for children's ALL and covers adult ALL. It is also poised to be the first domestic CAR-T product for pediatric ALL to receive market approval, showcasing its unique core strengths.

Fengke reporter: We’ve observed that Precision Biotech’s research pipeline is extensive, covering  both solid tumors and hematological malignancies, and leading the way in developing multiple first-in-class domestic therapies. Additionally, the majority of your pipeline has advanced to clinical stages, with a focus on highly innovative targets and indications. How has your company established such a comprehensive and efficient research and development system, ensuring rapid progression to clinical stages and sustaining a leadership position in target and indication innovation? Could you share the strategic thinking behind this approach?

Professor Qian Cheng: We believe that the development of therapeutic products needs to be grounded in a deep understanding of diseases. Our technical team is predominantly composed of experts from the field of tumor gene therapy. Over 30 years of continuous exploration and comprehension of tumors, coupled with our relentless pursuit and practical application of new technologies in gene and cell therapy, have equipped us with diverse perspectives and methods to create innovative treatment solutions.

I have also established an international team of experts through my 20 years of research and study experience in Europe. We have established a wholly-owned industrial technology research institute of the company, which specializes in applied research and transformation technology support, as well as the development of next-generation cell technology and future gene technology reserves. Our company has developed a comprehensive research and development pipeline that spans from early target discovery to product development, process and quality research, and clinical studies. This pipeline supports the rapid technological advancements required in gene and cell therapy, enhances our capacity for continuous innovation, and enables us to create unique CGT products for various targets and indications.

In the crowded CD19 target CAR-T field, Precision Biotech's Puzolcabtagene Autoleucel Injection is the first CAR-T treatment product in China for children's ALL and covers adult ALL. It is also poised to be the first domestic CAR-T product for pediatric ALL to receive market approval, showcasing its unique core strengths.

Fengke reporter: We’ve observed that Precision Biotech’s research pipeline is extensive, covering  both solid tumors and hematological malignancies, and leading the way in developing multiple first-in-class domestic therapies. Additionally, the majority of your pipeline has advanced to clinical stages, with a focus on highly innovative targets and indications. How has your company established such a comprehensive and efficient research and development system, ensuring rapid progression to clinical stages and sustaining a leadership position in target and indication innovation? Could you share the strategic thinking behind this approach?

Professor Qian Cheng: We believe that the development of therapeutic products needs to be grounded in a deep understanding of diseases. Our technical team is predominantly composed of experts from the field of tumor gene therapy. Over 30 years of continuous exploration and comprehension of tumors, coupled with our relentless pursuit and practical application of new technologies in gene and cell therapy, have equipped us with diverse perspectives and methods to create innovative treatment solutions.

I have also established an international team of experts through my 20 years of research and study experience in Europe. We have established a wholly-owned industrial technology research institute of the company, which specializes in applied research and transformation technology support, as well as the development of next-generation cell technology and future gene technology reserves. Our company has developed a comprehensive research and development pipeline that spans from early target discovery to product development, process and quality research, and clinical studies. This pipeline supports the rapid technological advancements required in gene and cell therapy, enhances our capacity for continuous innovation, and enables us to create unique CGT products for various targets and indications.

Fengke reporter: In the current industry landscape, many companies are accelerating their research and development by focusing on a fewer number of pipelines. However, Precision Biotech has managed to advance multiple pipelines at the same time. What strategic considerations drive this approach? How does the company ensure efficient resource allocation and smooth project execution while maintaining a broad portfolio, achieving a balance and collaborative progress across all pipelines?

Professor Qian Cheng: At present, Precision Biotech has been obtained the implied license of 4 CAR-T cells Class I new biological drug and 9 indications, and some new INDs are being applied for. The company has a strategic approach to pipeline progression, considering differentiated indications, targets, clinical protocols, and manufacturing technologies in its planning.

In advancing multiple pipelines, we have strategically considered the commercialization pathway of our products and the need for product iteration and updates. We’ve implemented different strategies for different pipelines to ensure efficient resource allocation and smooth project execution. Additionally, we are fortunate to have received significant support from our partners and the government, which to ensure that Precision Biotech can timely and systematically progress the clinical transformation and application of our product.

Fengke reporter: Looking forward to the future, how do you view the development prospects of cell therapies in China and their technological trends? What challenges are in urgent need of industry breakthroughs?

Professor Qian Cheng: Over the past decade, cell therapy in China has undergone significant development and has increasingly received support from national policies. The regulatory framework is being refined, and both clinical practitioners and the public are increasingly acknowledging the groundbreaking advancements offered by this technology. Despite the current industry-wide constraints, cell therapy, especially innovative treatment products, holds tremendous potential for growth. In the future, cell therapy products are expected to be highly competitive not only in oncology but also in the treatment of autoimmune diseases.

Certainly, improving the efficacy of treatments for solid tumors, overcoming technical challenges related to universal cell therapy products, and developing in vivo preparation techniques are areas that demand the collective efforts of scientists in the field.

Fortunately, recent developments in the industry show promising progress. Several products, including ours, have achieved significant breakthroughs in the clinical treatment of solid tumors. It’s believed that the full realization of any of these emerging technologies will propel the industry into a longer and more explosive growth phase.

Fengke reporter: Finally, there is a personal question. We see that you currently hold multiple positions, from academic responsibilities to being the Chairman and Chief Scientist at Precision Biotech. How do you manage to balance these diverse roles effectively?I think this is very learning for many start-up leaders.

Professor Qian Cheng：I believes that this issue should be examined from two perspectives. Firstly, at the professional level, engaging in teaching and research allows me to continuously explore the fundamental aspects of CGT, stay updated with the latest industry trends, and anticipate potential technological breakthroughs. Moreover, it enables to train more professionals for society and the industry, as well as to gather a stronger force for those who choose to contribute to enterprise development. Additionally, the transformation of biotechnology and its clinical application differ from traditional industries. For one, scientific decision-making requires professional foresight. Secondly, during the research and development phase, enterprise operations rely heavily on professionalism, necessitating expert coordination and the unified allocation of resources both within and outside the company to address bottlenecks and challenges throughout the process from project initiation to market launch.

At the team level, an individual’s energy is limited. You should arrange the necessitating prioritization in actions.I primarily focus on macro decision-making for the enterprise, providing strategic direction and overall coordination. The execution of specific tasks and professional matters are delegated to specialized teams. Consequently, diverse professional teams have been established to handle various aspects: from topic research and project execution to pipeline advancement, production management, quality research, project registration and declaration, and company operations. Each team is dedicated to their respective department, effectively organizing and driving the work forward.

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