RootPath Secures Nearly $50 Million in Series B Funding to Advance Gene Synthesis Platform for Cell Therapy Development

VCBeat (WeChat: vcbeat) has learned that RootPath, a synthetic biology and gene and cell therapy company, recently closed a Series B financing round of nearly $50 million. The round was co-led by CDH Investments and Yunjiu Capital, with participation from Hony Life Science Fund and continued investment from existing shareholder Matrix Partners China. Taihe Capital served as the exclusive financial advisor for this financing round.

This round of financing will be used to support the development and commercialization of Chengyuan Biotech’s high-throughput, long-fragment, high-accuracy gene synthesis products for arbitrary sequences, as well as to advance its personalized TCR-T therapy program—based on ultra-high-throughput TCR gene synthesis and functional validation technologies—into clinical development, including the construction of a GMP-compliant manufacturing facility in China suitable for investigator-initiated trials (IITs) and Phase I clinical trials.

Previously, Chengyuan Biotech disclosed that its seed and Series A financing rounds totaled nearly $20 million, with investors including Sequoia China, Matrix Partners China, Yuanhe Yuandian, Volcanic Stone Capital, Nest Capital, and Baidu Ventures.

Chengyuan Bio was incubated and established by Nest.Bio Ventures in 2017. Its team comprises scientists from top-tier institutions such as Harvard University and the Massachusetts Institute of Technology (MIT). As a synthetic biology and cell therapy technology developer, the company possesses a globally leading gene synthesis platform. This platform holds significant potential value in various fields, including cell therapies (such as TIL, TCR-T, CAR-T, and CAR-NK), macromolecular drugs, and gene therapy.

Regarding the value of next-generation gene synthesis technology in the pharmaceutical industry, Chen Xi, Co-founder and CEO of Chengyuan Bio, stated: “Since entering the 21st century, the pharmaceutical industry has been driven by two core forces: gene sequencing and gene synthesis.In short, one is reading and the other is writing. Over the past two to three decades, both of these core capabilities have improved at a pace exceeding Moore’s Law. However, there is a notable detail: the cost of “reading” has decreased far more rapidly than that of “writing.” Today, the cost of “reading” is five orders of magnitude lower than that of “writing.”

Chen Xi stated, “This gap has created a massive industry-wide demand for ‘writing.’ In many cases, we do not understand the sequences ‘read’ from nature. We must therefore conduct wet-lab experiments in the physical world to comprehend and interpret these sequences, which necessitates gene synthesis. Current technologies are far from meeting this demand. For instance, the GenBank database alone contains trillions of base pairs of DNA sequences. Countless high-value sequences with significant potential for drugs, research tools, metabolic engineering enzymes, and pathways are hidden within it. However, with existing technologies, each experiment can only synthesize genes ranging from thousands to tens of thousands of base pairs. Coupled with high synthesis costs, this severely limits our ability to fully unlock these potential values.”

Meanwhile, Chengyuan Bio leverages its independently developed PathFinder^TMplatform that enables the parallel assembly of thousands of gene fragments in a single reaction with effective error correction, thereby reducing the synthesis cost of long genes (i.e., those exceeding 1 kb) by one to two orders of magnitude below the current state-of-the-art global technology level. This breakthrough technology can address several pain points in current new drug development.

In PathFinder^TMBuilding on this platform, Chengyuan Bio has constructed the world’s largest fully synthetic T cell receptor (TCR) library derived from tumor-infiltrating lymphocytes (TIL-derived Fully Synthetic TCR Library), and has identified multiple TCRs with potent tumor-killing activity from this library. Related product pipelines are rapidly advancing toward clinical development.

In this regard, Chen Xi stated, “In the field of cancer immunotherapy, with the advancement and widespread adoption of single-cell sequencing technologies, it has become standard practice in contemporary immunological research to simultaneously obtain TCR sequences and transcriptomic data from thousands of T cells. However, the truly critical information lies in identifying which of these TCRs genuinely recognize tumor antigens. This requires large-scale TCR gene synthesis and wet-lab validation. By addressing this challenge, we can identify multiple autologous, tumor-reactive, safe, and effective TCRs for each patient. This is precisely what PathFinder”^TMthe platform’s arena for application.”

Currently, Chengyuan Biotech has fully validated the PathFinder-based^TMThe technical capability to synthesize arbitrary genes, particularly the de novo synthesis and screening of high-throughput TCR libraries. Following this financing round, Chengyuan Bio plans not only to complete the preliminary clinical validation of personalized TCR-T therapy within two years, but also to achieve industrialization and commercialization of high-throughput synthesis of long genes with arbitrary sequences, while establishing a diversified R&D pipeline.

It is reported that Chengyuan Bio has established collaborations with several leading research institutions and pharmaceutical companies, and is poised to announce a world-class Scientific Advisory Board. In terms of project development, the company has assembled an experienced medical and manufacturing team and is currently constructing GMP-compliant facilities to support the clinical development of its subsequent pipeline.

In the future, Chengyuan Bio will remain committed to decoding life at the metagenomic level through ultra-high-throughput gene synthesis.

Cao Darong, Founding Partner of Yunjiu Capital, stated:“The founding team of Chengyuan Biotech, led by Dr. Chen Xi, boasts extensive expertise in gene synthesis technology and a profound understanding of immune cell therapy. Its independently developed, low-cost, high-throughput gene synthesis platform offers distinct advantages and broad application scenarios, holding significant market value in fields such as cell therapy, gene therapy, and antibody engineering. We are also pleased to see that, based on PathFinder”^TM“The platform’s TCR-T cell therapy pipeline is poised to enter the clinical research phase, with expectations that it will address more unmet clinical needs in the field of solid tumors and bring new hope to more patients.”

Ms. Huang Jingjing, Project Leader at CDH Investments, and Dr. Liu Dan stated:“We are excited about Chengyuan Biotech’s breakthrough in the field of gene synthesis. While the cost of gene sequencing has dropped rapidly, long-fragment, low-error-rate gene synthesis has remained a bottleneck for both industry and technology, limiting its applications. Chengyuan Biotech has achieved a breakthrough in this area and pioneered its application in cell therapy. We anticipate that this synthetic biology design of polyclonal TCR-T cells, which leverages the advantages of TILs, will introduce novel therapeutic strategies for solid tumors, significantly improving both success rates and safety.”

Dr. Yu Zhiyun, Partner at Matrix Partners China, stated:“Since our lead investment in Chengyuan Bio during the previous funding round, the team led by Dr. Chen Xi has demonstrated exceptional scientific expertise and strong execution capabilities. The company’s long-chain DNA synthesis capabilities have reached world-class standards, with costs significantly lower than those of international counterparts. Furthermore, the company has successfully applied this DNA synthesis prowess to oncology therapeutics, enabling the rapid and cost-effective large-scale identification of personalized TCRs effective for cancer patients. We look forward to Chengyuan Bio, as a leading player in synthetic biology, continuing to deliver surprising advancements to the industry.”

Sun Si, Director at Taihe Capital, stated:“The cost of long-chain DNA gene synthesis is a core bottleneck in many drug R&D scenarios. Chengyuan Bio possesses a world-leading technology platform that can significantly reduce costs, thereby unlocking a vast market. We are delighted to serve the company in this round of financing and look forward to the first PathFinder-based”^TM"The platform's TCR-T cell therapy has achieved breakthrough results in clinical trials."

CDH Investments, established in 2002, is one of the most influential alternative asset management firms in China. To date, its assets under management have reached RMB 170 billion. CDH Investments operates six major business segments: private equity, venture and growth capital (VGC), public securities investment, real estate investment, mezzanine investment, and wealth management. The firm has invested in more than 200 companies, over 70 of which are listed domestically and internationally, nurturing a cohort of industry-leading brands. Guided by its core philosophy of “partnering with strivers to create long-term value,” CDH Investments is committed to becoming a long-term partner for global investors in identifying premier investment opportunities, a value-creation partner for its portfolio companies, and an accelerator for China’s industrial transformation and the enhancement of people’s quality of life.

Sky9 Capital is a leading venture capital fund focused on innovative themes in consumption, the internet, hard technology, enterprise services, and healthcare. The Sky9 Capital team comprises seasoned technical experts, successful entrepreneurs, and investors. Since 2011, the team has managed multiple USD and RMB funds, with assets under management nearing $2 billion.

Hony Capital was established in 2003 and is a leading investment management firm in China. Guided by its mission of “Pooling Intelligent Capital to Create Value,” the firm currently operates across multiple business segments, including private equity, real estate investment, hedge funds (Jinyong Investment), public mutual funds (Hony Yuanfang Fund), and venture capital. Committed to aggregating high-quality domestic and international capital to support the development of the real economy, Hony Capital manages total assets under management of RMB 100 billion. Focusing on the Chinese market, Hony Capital has invested in over one hundred Chinese and foreign enterprises in sectors such as healthcare, consumer goods and dining, culture and entertainment, environmental protection and new energy, advanced manufacturing, and commercial properties. The healthcare industry has been one of the earliest investment sectors for Hony Capital since its inception, and the firm has systematically built a comprehensive portfolio spanning pharmaceuticals, medical devices, and healthcare services.

Matrix Partners China, established in 2008, is a leading venture capital firm in China. Over the past decade since its inception, it has remained deeply rooted in the local market, steadfastly supporting Chinese entrepreneurs. Matrix Partners China has invested in more than 700 companies to date. Notable portfolio companies include XPeng Motors, Li Auto, Futu Securities, Guazi Used Cars, Youzan, Ronbay Technology, XGIMI Technology, Momo, Ele.me, Peijia Medical, Kymab Diagnostics, Genor Biopharma, Career International, LexinFintech, PingCAP, Zihai Guo, Simple Love, iSpace, SemiDrive Technology, Taimei Medical Technology, and Drug Research Club.