Fanen Bio Completes Nearly RMB 100 Million Pre-A Financing to Advance IND Submissions and Phase I Trials of Personalized TCR-T Therapies for Solid Tumors

VCBeat learned第一时间 that recently, Guangzhou Fan恩 Biotechnology Co., Ltd. ("Fan恩 Biotech") has completed a nearly 100-million-yuan Pre-A round of financing. This round of financing was led by Huafang Capital, with participation from Ruifu Venture Capital and Yabao Pharmaceutical, and Junyi Capital serving as the exclusive financial advisor. The financing funds will be mainly used for IND applications and Phase I clinical trials of multiple cell therapy products of Fan恩 Biotech.

Founded five years ago, this is the first time that Fanen Biotech has actively disclosed its financing information and R&D progress to the public.

What "Hardcore" Stories Are Behind This "Low-Key" Company? VCBeat's New Medicine Team Interviewed Professor Penghui Zhou, Founder of Pan-Eng Bio, at the First Opportunity.

In 2014, he returned to China, and in 2017, he founded Pan-E Bio. Zhou Penghui and the core team members have long been focused on refining the technology and have established personalized TCR-T cell therapy.

On February 24 this year, the relevant research findings were published online in Cell Research.

The study utilized Tas cells (Tumor antigen-specific T cells) produced by the patient's own immune system to attack tumors.The first personalized TCR-T cell therapy was established.Capable of simultaneously targeting multiple tumor antigens.

In terms of underlying technical logic, Fanen Bio has a core discovery."We can clearly distinguish which T cells in tumor tissues are capable of recognizing tumor antigens and have the ability to kill tumors, and which T cells are 'bystanders' without the ability to attack tumors. This was impossible to differentiate in the past. Traditional TIL cell therapy not only had a low success rate in cultivation but also most of the T cells cultured from tumors were bystander T cells," explained Zhou Penghui. "This means that most of the cells subsequently infused into patients are ineffective, resulting in insufficient efficacy of the product. After establishing this core technology, it is possible to accurately obtain the patient's own anti-tumor T cells for personalized TCR-T cell preparation."

FanEn Bio has comprehensively optimized the preparation process of personalized TCR-T cells and completed the development of GMP production technology, enabling the preparation of personalized polyclonal TCR-T cells targeting multiple tumor antigens for patients in approximately 6 weeks.This therapy targets the unique tumor antigens of the patient,不受已知抗原靶点的限制, and is suitable for all types of solid tumors.

Apart from Pan-Eng Bio, there are currently multiple companies worldwide developing personalized TCR-T cell therapy technology.

Compared with these companies, FanEn Bio uses its unique technology to directly isolate and clone TCRs that recognize tumor antigens from tumor tissues, enabling the preparation of personalized TCR-T cells in a relatively short period. The TCRs used in this therapy are derived from the patients themselves and target neoantigens and other tumor-specific antigens. Compared with traditional TCR-T therapies that primarily target tumor-associated antigens, which are highly expressed in tumors but also present in normal tissues, this approach offers higher safety and efficacy. It has already demonstrated significant therapeutic effects in IIT clinical trials. The preliminary IIT clinical trials have also provided FanEn Bio with extensive experience in personalized TCR-T cell therapy, facilitating the smooth progress of subsequent IND clinical trials.

At the same time, FanEn Bio will introduce a multi-gene combination to remodel the solid tumor microenvironment, further enhancing the therapeutic effect of this product on solid tumors.

Before starting his business, Zhou Penghui firmly chose the high-barrier field of solid tumors for breakthrough. "Although certain effects have been observed in past clinical trials of cell therapy in solid tumors, the overall efficacy has not been very good, mainly because the immunosuppressive microenvironment of solid tumors strongly suppresses anti-tumor immune responses.""My previous main research direction was to relieve the suppression of anti-tumor immune responses by the solid tumor microenvironment. Therefore, our company has continued research in this area by precisely engineering T cells to work continuously and efficiently within solid tumors."

Zhou Penghui further explained, "The current mainstream of cell therapy mainly focuses on the selection and modification of CAR and TCR. Although there are also improved products with the addition of a single auxiliary gene, they lack the ability to comprehensively resist and modify the solid tumor microenvironment, resulting in limited therapeutic effects in solid tumors."

To address this technical challenge, FanEn Bio utilized a high-throughput screening platform (HAP) covering the entire genome to systematically study the impact of each gene on T-cell migration, proliferation, function, and microenvironment modification within the tumor microenvironment. Finally, through the whole-genome T-cell signal optimization technology platform (GSOP), the optimal gene combination was obtained, comprehensively enhancing the capabilities of CAR-T and TCR-T cells in tumor infiltration, sustained proliferation and killing efficiency, and remodeling the tumor microenvironment, achieving effective treatment of solid tumors.

One of Pan-E Bio's main innovations is the multi-gene modification of T cells themselves to make them more adaptable to the tumor microenvironment.This multi-gene modification system targeting the solid tumor microenvironment is suitable for most types of solid tumors. It has been successfully applied to Pan-Immune Bio's personalized TCR-T cell therapy, as well as multiple TCR-T and CAR-T cell therapy products targeting known antigens, demonstrating significantly enhanced efficacy in preclinical animal experiments and IIT clinical studies.

In addition, to address the current widespread issue of high costs in cell therapy, FanEn Bio has invested significant efforts in developing targeted in vivo delivery technologies for CAR and TCR, avoiding the complex processes of ex vivo preparation of CAR-T and TCR-T cells, thereby significantly reducing the cost of cell therapy. After extensive testing and optimization of various materials and methods, FanEn Bio has successfully achieved efficient T-cell delivery in animal models and is currently preparing to apply for IIT research, with plans to initiate human trials in the near future.

When Zhou Penghui first entered the field of tumor immunology, it was not yet widely recognized. He recalls that at the time, due to the small number of researchers in this area, a global conference on tumor immunology was held only once every two years. The attendees included most of the researchers working on tumor immunology in research institutions and companies, and the total number of participants was only three to four hundred.

It was not until 2011, when CTLA4 monoclonal antibody demonstrated significant efficacy in clinical settings, that the field of immunotherapy gradually gained momentum. In 2014, after Penghui Zhou completed his postdoctoral work at the Dana Farber Cancer Institute of Harvard Medical School, he began looking for jobs. Every institution and company he interviewed with extended an offer to him, which sufficiently illustrates how scarce talent is within the industry.

However, Zhou Penghui still decided to transform his years of technical accumulation into product applications himself. "My goal is to translate basic research results into clinical applications. In the process of developing basic research findings into drugs, only by personally participating in the transformation process can many technical details be quickly resolved, accelerating the product's R&D progress."

Zhou Penghui knows deeplyDrug development must be based on the close integration of basic research and clinical research.At the end of 2014, he returned to China and joined the Cancer Center of Sun Yat-sen University. The hospital has a solid foundation in both basic research and clinical application, allowing him to continue his translational research on the treatment of solid tumors. The patents obtained from the research results at the Cancer Center of Sun Yat-sen University have also been gradually transferred to the company, fully leveraging the advantages of industry-university-research cooperation.

In terms of technology transfer, Zhou Penghui has learned a great deal from his former mentor.

During his Ph.D. studies in immunology at the University of Michigan, Penghui Zhou was mentored by renowned immunologists Professor Yang Liu and Professor Pan Zheng. The two professors are the founders of OncoImmune and successfully developed the CD24Fc protein drug for treating COVID-19 and stem cell transplant rejection, as well as a novel CTLA-4 antibody with low side effects. Among these, the CD24Fc protein drug has been licensed to Merck for $425 million, and the novel CTLA-4 antibody has entered Phase I clinical trials simultaneously in China and the United States.

During his postdoctoral research at Harvard University, his collaborator and mentor Professor Nir Hacohen founded Neo Therapeutics, the world's first neoantigen cancer vaccine company, while another professor, Gleen Dranoff, later became the Global Director of Cancer Immunology at Novartis.

Years of conducting research with his mentors have made Zhou Penghui profoundly aware that solid fundamental research is a precondition for the successful transformation of a product. "Take my doctoral advisor as an example—they had already conducted years of basic research on the CD24FC protein before developing it into a protein drug."

With an understanding of industrial transformation, Zhou Penghui founded Fanen Biotech in 2017. He understood that "research achievements must be transformed into products applied in clinical settings to truly help patients. Therefore, it is essential to rely on professional drug development companies to complete the transformation from technology to product and promote its clinical application."

When the cell therapy market was booming, he also faced temptations. After the company platform and production workshop were set up, it was a time when CAR-T companies targeting blood tumors were "all over the place," and friends also advised him, "Quickly launch a few similar products."

However, Zhou Penghui is well aware that while the CAR-T cell therapy technology for blood tumors is relatively mature, the market capacity for blood tumors is limited. On the other hand, cell therapy for solid tumors has yet to see a breakthrough, with low efficacy rates and high technical barriers. His long-term accumulation in the research of the solid tumor microenvironment has already laid the foundation for overcoming solid tumors.

Moreover, unlike other companies, FanEn did not enter the capital market right after its establishment. From 2018 to 2021, Zhou Penghui and a few like-minded friends invested more than 18 million yuan, spending four years refining the platform and products, building factories, and assembling a team. Meanwhile, the company also received strong support from the Huangpu District Government of Guangzhou City.

Until 2021, "we have basically solved several core issues in the treatment of solid tumors. The first is the immunosuppressive microenvironment of solid tumors. We achieved a stable multi-gene modification model through whole-genome screening and combination. The second is the limited target issue. Traditional TCR-T and CAR-T therapies are directed against a single target, most of which are non-mutated tumor-associated antigens. Since these targets are only expressed in a small number of patients, the majority of patients still cannot be treated. Through technological breakthroughs, we can now customize personalized TCR-T cell therapy for each patient's unique tumor antigens, expanding the application of TCR-T cell therapy to most patients with solid tumors."

After Panngene Biotech solved the core bottleneck of solid tumors and the product took shape, Zhou Penghui decided it was time to introduce external capital.

"Scientific research and drug development are completely different"Zhou Penghui remarked, "In scientific research, researchers can spend years digging deep to solve just one problem. But in drug development, it’s necessary to organize efforts so that everyone has an appropriate role, based on precise calculations of the development process."StrictFollowDrug Research and Development Process,"Ensure the successful advancement of the pipeline to clinical and commercial stages within a specific timeframe."

Investors are most concerned about whether the company's pipeline can proceed smoothly according to the corresponding schedule, and whether the company can become profitable and go public.Therefore, Panacea Biotech has also developed its own strategy, a pipeline advancement model that combines "relatively simple" with "complex."

To truly establish themselves in the field, companies must possess some products with cutting-edge technology, but these products often require substantial research and development funding and long R&D cycles. To balance this long-term investment of time and capital, Pan-E Bio has developed some relatively "simple" R&D pipelines to quickly enter the market and gain the ability to recover.

Zhou Penghui smiled and said, "Although they are all 'hard bones to chew,' starting with the ones that have some meat on them is crucial for a company's sustainable development."

Currently, Fanen Biotech has five pipelines under research.The fastest progressing is the TAL (Tumor-Associated Lymph Node T-cell) pipeline. This pipeline targets all subtypes of solid tumors, offering advantages such as low treatment cost and significant efficacy. The tumor antigen-specific T-cell enrichment and culture technology used in this pipeline is a core technology independently developed by Pan-E Bio, and patent protection has already been initiated.

Overall, FanEn Bio's TAL and TIL cell therapy pipelines both utilize proprietary patented technologies for enriching tumor antigen-specific T cells and inducing memory cell differentiation. These technologies offer advantages such as no genetic modification, high culture success rates, and a high content of tumor antigen-specific T cells.

The individualized polyclonal TCR-T product is the core product that FanEn Bio will focus on developing in the long term.

After this round of financing, Fanen Bio will fully advance all its R&D pipelines into IND.Currently, the entire company's focus has shifted entirely to the clinical application and clinical trial segments.In order to support the current preclinical experiments and subsequent clinical trials, Fanen Biotechnology has established cooperative relationships with multiple medical institutions, including the Cancer Hospital of Sun Yat-sen University, Guangdong Provincial People's Hospital, Cancer Hospital of Fudan University, First Affiliated Hospital of Sun Yat-sen University, Peking University Cancer Hospital, and Guangdong Provincial Traditional Chinese Medicine Hospital, to carry out various tumor research and technology application projects.

Tilting Pan-Earth Biotech's core resources towards TCR-T is not only because Zhou Penghui, as a scientist-turned-entrepreneur, is aiming to transform the most cutting-edge technology, but also because he believes that TCR-T is one of the biggest directions for future solid tumor treatment."CAR-T has achieved disruptive results in hematological tumors, making immune cell therapy a beacon of hope for cancer treatment; however, the current immune cell therapy shows unsatisfactory effects on the vast majority of solid tumors. Although companies in the market have their own technical expertise, there have been no reports of disruptive technologies so far."

Promising tracks naturally attract the layout of numerous companies. According to incomplete statistics, there are currently several companies in China布局TCR-T领域, such as泛恩生物 (Fanen Bio), 华夏英泰 (Huaxia Yingtai), 可瑞生物 (Kerui Bio), 香雪制药 (Xiangxue Pharmaceutical), 天科雅 (Tiankeya), 因诺免疫 (InnoImmune), 金斯瑞生物 (GenScript Biotech), and 新景智源 (Xinjing Zhiyuan). Facing this high-barrier field, behind every company, there is one or more immunologists providing technical support. "The immunology circle is just this big. Basically, the immunologists in these domestic companies are our peers in the scientific research community," Zhou Penghui chuckled.

For the entire cell therapy field, Zhou Penghui believes that the most anticipated event this year is whether Iovance's lifileucel (Tumor Infiltrating Lymphocyte (TIL) therapy) can be approved this year. Previously, the development progress of lifileucel has not been smooth, and its listing application repeatedly failed to reach an agreement with the FDA. Affected by this, Iovance's stock price has fluctuated several times. If lifileucel can be successfully approved this year, it will completely ignite a raging fire in the cell therapy industry.

"In addition, in the field of solid tumors, TCR-T will陆续 have some Phase II and Phase III clinical results coming out, and there should be some good outcomes," said Zhou Penghui.

The field of cell therapy continues to be highly active, but where does original innovation come from? Zhou Penghui has his own perspective: "It still needs to start from basic research to find its origin. Our innovation is nothing more than solving problems in the field that have yet to be addressed. If you break through any bottleneck, that is original innovation."

Huafang CapitalWe are delighted to have the opportunity to collaborate with FanEn. Professor Zhou, as a scientist with decades of experience in tumor immunology research, possesses convincing and solid academic expertise, a keen insight into international R&D advancements, and unique perspectives and innovative ideas on immune cell therapy. T cells, as the natural effector cells of adaptive immunity, play a central role and have a decisive impact in tumor immunotherapy. Following the tremendous success of CAR-T in treating hematologic malignancies, solid tumors have become a key focus of R&D within the industry. As a fund that continuously focuses on the cell and gene therapy sector, Huafang firmly believes that TCR-T is an essential approach in immune cell therapy for ultimately overcoming solid tumors. Despite the variety of technical pathways, we are pleasantly surprised by the extensive, robust, and highly innovative research conducted by FanEn in areas such as TCR screening and overcoming the suppression of T cells by the tumor microenvironment. This significantly enhances the potential for breakthroughs in its pipeline products for immune cell therapy targeting solid tumors.

VCBeatWe are very pleased to have the opportunity to cooperate with FanEn. Professor Penghui Zhou has decades of research experience in tumor immunotherapy and a profound understanding of the bottlenecks in solid tumor cell therapy. Under the leadership of Professor Zhou, FanEn has developed multiple targeted technology platforms and has several potential First-in-Class products under development.

Yabao PharmaceuticalProfessor Zhou Penghui focused on T cell function research during his studies and work at the University of Michigan and Harvard University, where he established a systematic screening method for T cell activity regulators. After returning to China, he further conducted in-depth research on related scientific issues and began exploring industrial applications. Meanwhile, the founding members of his team come from top medical schools worldwide, with extensive experience in immunotherapy research and development. We highly agree with Professor Zhou’s insights into the numerous challenges and innovative solutions in the current development and practice of TIL and TCR-T therapies, and we deeply admire his team's spirit of innovation. We look forward to Pan-Immune Bio achieving breakthrough progress in innovative T cell-related immunotherapies under the leadership of Professor Zhou’s team.

Huafang Capital was established in 2017 as a fund manager focused on early-stage investments in the biopharmaceutical and advanced manufacturing sectors. Its core team members have over two decades of deep involvement in the pharmaceuticals industry, possessing extensive knowledge of the sector. They offer profound insights into project innovation, differentiation, and the capabilities of entrepreneurial teams. To date, they have completed investments in more than thirty projects. Leveraging the abundant industrial resources of Huali Group, which has multiple listed companies in the biopharmaceutical and advanced manufacturing fields, Huafang Capital provides comprehensive support to its portfolio companies, helping them rapidly grow into leading enterprises within their respective niches.

Panacea Venture is a venture capital firm formed by the life sciences investment team of KPCB CHINA and industry veterans, focusing on investing in early-stage and growth-stage healthcare and life sciences companies.

Yabao Pharmaceutical Group Co., Ltd. is a group company with a history of more than 40 years, listed on the A-share of the Shanghai Stock Exchange in 2002. As a high-tech enterprise, Yabao Pharmaceutical is recognized by the Ministry of Industry and Information Technology as one of the "Top 100 Pharmaceutical Industrial Enterprises in China," with its innovation capability ranking among the top 20. In recent years, the company has focused on innovative drugs as its leading sector, guided by clinical needs, introduced high-end talents, and built an international R&D team. It has established a national recognized enterprise technology center, a postdoctoral research workstation, and an academician workstation. The company owns more than 1,000 intellectual property rights, including authorized patents, registered trademarks, and copyrights. Yabao Pharmaceutical firmly fosters core competitiveness through world-class scientific and technological innovation capabilities and takes internationalization as its strategic development direction. It introduces international talents, builds international platforms, and advances towards internationalization in an all-round and multi-model manner.