Zhuancode Bio Secures Tens of Millions in Seed Funding to Advance Proprietary Ultra-Compact Gene Editor alphaCas®

VCBeat has learned that CASTALYSIS BIOSCIENCE, a leading gene-editing company, recently completed a seed funding round worth tens of millions of RMB, exclusively led by Med-Fine Capital.The funds raised in this round of financing will be primarily used for the development and advancement of the gene editing pipeline, as well as the construction of an ultra-compact editor platform.

CASTALYSIS BIOSCIENCE, founded in 2023, is dedicated to the clinical translation of highly efficient ultra-compact gene editors into “one-and-done” curative gene therapies. The company possesses alphaCas, a globally leading ultra-compact and highly efficient gene editor.^®A metagenomics-based gene editor mining platform, featuring engineering capabilities for ultra-compact gene editors and rapid target screening and pipeline development. Leveraging cutting-edge gene editing technologies, CASTALYSIS BIOSCIENCE is dedicated to expanding gene editing therapies from genetic disorders to common chronic diseases, developing best-in-class and first-in-class novel drugs.

In 2023, the world’s first gene-editing therapy, Casgevy, received FDA approval for market launch, injecting a strong boost into the field of gene-editing therapies and spurring deeper exploration and innovation in this sector. Many innovative gene therapy companies have begun shifting from ex vivo gene editing to tackling the challenges of in vivo gene editing, driving a new wave of research and development in novel gene editors and delivery systems. As a result, gene-editing therapies have entered a period of rapid growth. CASTALYSIS BIOSCIENCE, armed with breakthrough gene-editing technology, has seized the opportunity amid this surge.

Before founding CASTALYSIS BIOSCIENCE, Dr. Yan Ming, CEO of the company, had already accumulated extensive industry experience in the gene editing sector.

After completing his postdoctoral fellowship at UCLA, Ming Yan joined Calimmune, a U.S.-based gene therapy company specializing in hematopoietic stem cells, where he was primarily responsible for advancing the company’s clinical programs and leading the research and development of new pipelines.

In 2017, Calimmune was acquired by CSL Behring, a global leader in plasma-derived therapies, due to its outstanding technological innovations and cutting-edge products. Yan Ming joined the company and participated in establishing CSL Behring’s new drug R&D department for gene therapy, gaining more direct insight into the clinical challenges of gene-editing therapies.

He and his team recognized that the high production costs of ex vivo gene editing hindered its widespread adoption and application among a broader patient population, leading them to propose a new drug project focused on in vivo gene editing.

At that time, to promote in vivo gene editing therapies with greater focus and precision, Yan Ming and his team evaluated more than 20 gene-editing biotech companies worldwide and conducted a comprehensive survey of all available gene editors. Unfortunately, none of the existing gene editors truly met the R&D requirements for in vivo gene editing at that time.This also planted a seed in Yan Ming’s mind—to find a gene editor compatible with in vivo gene editing, thereby achieving the goal of “one-time treatment, lifelong cure.”

In 2020, Yan Ming joined Rampart Bioscience, a biotechnology company focused on in vivo gene therapy for genetic diseases, as an early team member. During his tenure, Yan Ming spearheaded the development of Rampart Bio’s pipeline data and technology platform, which helped the company secure $125 million in financing and attract interest from prominent U.S. venture capital firms such as OrbiMed and Forbion.

Nevertheless, Yan Ming remains committed to further improving the delivery methods of gene-editing drugs, aiming to develop a gene-editing therapy that eliminates the need for repeated dosing. By offering lower costs, greater therapeutic efficacy, and enhanced safety, he seeks to make gene-editing therapies accessible to a broader patient population.

In the summer of 2023, Yan Ming met Professor Quanjiang Ji of ShanghaiTech University and Dr. Lingquan Deng, a partner at Med-Fine Capital, and learned that Professor Ji’s team was developing alphaCas, an ultra-compact, high-efficiency gene editor.^®“Professor Ji is an internationally renowned expert in the field of gene editors. As a leading figure in ultra-compact editors in China, he made the initial original scientific discoveries for CASTALYSIS BIOSCIENCE, laying a solid technical foundation for the company’s development,” said Yan Ming.

Yan Ming instantly recognized the revolutionary impact of Ji Quanjiang’s technology platform on in vivo gene editing, marking the beginning of CASTALYSIS BIOSCIENCE’s entrepreneurial journey.

Currently,Yan Ming serves as CEO, overseeing the company’s operations, financing, and pipeline R&D. Ji Quanjiang joined CASTALYSIS BIOSCIENCE as its Scientific Founder, with Professor Ji’s team participating in the development of alphaCas.^®Dr. Wu Zhaowei, who made the original discovery, serves as CTO, overseeing the iterative upgrades of the technology platform, while Dr. Lin Junliang (formerly Senior Scientist for Gene Editor Development at Metagenomi in the United States) is responsible for business development.

Achieving more affordable pricing, greater efficacy, and enhanced safety for gene-editing therapeutics is the founding mission of CASTALYSIS BIOSCIENCE.Breakthrough PerformanceGene EditoralphaCas^®, which serves as the most fundamental cornerstone for CASTALYSIS BIOSCIENCE's presence in the gene editing field.

“alphaCas^®“In fact, it is entirely an original Chinese innovation. It was discovered within Chinese territory, derived from the sequence of a microorganism found on a sponge in the South China Sea, and academically named AcCas12n. Professor Ji had already embarked on related research in 2021,” introduced Yan Ming.

alphaCas^®The advantages of the editor are mainly reflected in two aspects: one is its ultra-compact size, and the other is its high efficiency.

Currently,Traditional CRISPR-Cas9 and Cas12a editors are both relatively large in size,Approximately between 1,300 and 1,400 amino acids in length, but CASTALYSIS BIOSCIENCE'salphaCas^®The size of the editor can be reduced to under 500, which is only 1/2 or even 1/3 the size of these large gene editors.

While being smaller in size, alphaCas^®It still ensures robust activity. Nowadays, numerous biotech companies are focusing on innovations in compact gene editors; despite significant efforts in miniaturization, they fail to guarantee the activity of the gene editors. AlphaCas^®The development pathway of the editor differs from that of traditional gene editors, achievingDual Consideration of Miniaturization and High Activity。

alphaCas^®The leading edge of this gene editor extends even further, endowing CASTALYSIS BIOSCIENCE’s gene-editing therapies with a broader range of application scenarios. Due to its small size,alphaCas^®Various operation attachments can be added,Its compact size allows it to be packaged into a single AAV viral vector, facilitating efficient extrahepatic gene editing.This overcomes the current limitation of requiring two AAV vectors to deliver editors, marking a significant leap forward.

Additionally,Non-viral vectors such as LNPs are an essential pathway to achieving low-cost, safer in vivo gene editing.Compact gene editors mainly consist of two components: a protein and gRNA. Currently, the gRNAs of many compact gene editors under development are relatively large, exceeding 200 nucleotides in length, which makes large-scale chemical synthesis difficult and limits their application in non-viral vector delivery. However, CASTALYSIS BIOSCIENCE has developed alphaCas^®The gRNA size is reduced by one-third, enabling cost-effective manufacturing, which allowsalphaCas^®It can also meet the delivery requirements for non-viral vectors such as LNPs., and due to the advantage of its small size, it can reduce dosage requirements and mitigate side effects caused by the delivery system.

Thus, alphaCas^®It possesses multi-dimensional potential—applicable to both non-viral vectors and viral delivery platforms—with its development pipeline covering both liver-targeted and non-liver-targeted directions.

Yan Ming mentioned that alphaCas^®This represents a highly promising scientific discovery, yet at its inception, it remained far from becoming a genuine gene-editing therapeutic. However, in recent months, Dr. Wu Zhaowei of CASTALYSIS BIOSCIENCE has achieved significant breakthroughs in engineering, further optimizing alphaCas.^®The compact size of the gene editor addresses the druggability challenges associated with non-viral vector delivery, culminating in the development of alphaCas.^®From Original Scientific Discoveries to Phased Breakthroughs in Druggability.

Due to alphaCas^®This is an original Chinese innovation. It not only follows a development path distinct from other gene editors, thereby establishing an extremely robust technical barrier for CASTALYSIS BIOSCIENCE, but also ensures very low homology with other editors. Therefore,Drug development strategies based on this editor will be highly differentiated, with disease-specific targets that are entirely distinct from those currently pursued by various companies.

This confers a core advantage: for drugs currently under development by other small-molecule gene editors, CASTALYSIS BIOSCIENCE can develop therapeutics targeting the same sites but with significant advantages in dosage, toxicity, and manufacturing costs, thereby creating best-in-class products. Furthermore, for targets that are undruggable by other gene-editing platforms, CASTALYSIS BIOSCIENCE can pioneer novel approaches to develop first-in-class pipelines.

“Ultra-compact gene editors are an essential pathway for in vivo gene editing.”Yan Ming mentioned.

“Gene editors are very much like operating systems. Ex vivo gene editors are more akin to the operating systems of large machines such as computers, whereas in vivo gene editing requires a more streamlined and efficient operating system, similar to that of a smartphone. Currently, many gene-editing companies hope to achieve in vivo gene editing using traditional gene editors such as CRISPR-Cas9, which is equivalent to adapting a computer operating system for use on a smartphone—a task of extremely high difficulty.” Yan Ming used this vivid analogy to explain the importance of ultra-compact gene editors: “To develop a promising in vivo gene-editing therapeutic, improvements must start from the ‘operating system.’ AndUltra-compact, highly efficient gene editors are essential to truly drive the iteration of gene-editing therapeutics in terms of low dosage, low toxicity, and high applicability.”

This is also the primary reason why CASTALYSIS BIOSCIENCE regards ultra-compact gene editors as a key direction for gene-editing therapeutics. Although the world’s first gene-editing therapy has already been launched, its side effects cannot be overlooked; whether viral or non-viral vectors are used, they may trigger immune and inflammatory responses in vivo. Consequently, in current clinical trials of in vivo gene-editing drugs, patients are typically administered multiple immunosuppressive agents to mitigate or alleviate these side effects.

Under conditions of equal molar concentration,Ultra-compact gene editors offer significant advantages in dosing, substantially reducing drug-related side effects. This means that, beyond genetic disorders, CASTALYSIS BIOSCIENCE can extend gene-editing therapies to chronic and even common diseases.

Compared with genetic diseases, the patient population for chronic and common diseases is larger, the treatment cycle is much longer, and the control of toxic side effects is more stringent; thus, the significant importance of ultra-small gene editors is self-evident.

Having addressed drugability issues, CASTALYSIS BIOSCIENCE will next focus on validating alphaCas.^®Address the efficacy of gene editors in in vivo animal models and resolve CMC manufacturing process issues. The company will further expand the platform’s application scope and promote the validation of ultra-compact gene editors for effective non-viral vector delivery.

According to the introduction, currently alphaCas^®“It has already demonstrated advantages in terms of dosing and safety in the field of genetic diseases. In this field, we have established a pipeline covering several indications. Our lead program, utilizing liver-targeted non-viral vectors, has shown therapeutic potential. Meanwhile, we have also expanded our portfolio to include non-liver-targeted therapies and neurological disorders,” said Yan Ming.

In addition to building its own proprietary technology platform, CASTALYSIS BIOSCIENCE is also actively expanding external collaborations. In the future, beyond genetic diseases, CASTALYSIS BIOSCIENCE will dedicate itself to applying alphaCas^®Expanding the application of gene editors to chronic and common diseases with larger patient populations, and developing more gene-editing therapies with enhanced safety and superior efficacy to benefit a broader range of patients.

Regarding this financing round, Dr. Deng Lingquan of Med-Fine Capital, the exclusive lead investor in this round, stated:“The foundational role of next-generation gene-editing tools, specifically Cas proteases, in the innovative field of cell and gene therapy is somewhat comparable to that of microchips in the high-tech industry. While this domain was initially pioneered and created by scientists in Europe and the United States, it is encouraging to see Chinese scientists rapidly catching up and achieving world-class research outcomes. Professor Quanjiang Ji from ShanghaiTech University is a rising star in this field. In 2021, Professor Ji published an article in a Nature subsidiary journal, reporting the smallest Cas protein with editing activity known globally at the time. Subsequently, in 2023, he reported in a Cell subsidiary journal the novel miniature CRISPR-Cas12n family nucleases with clear independent intellectual property rights for the first time worldwide. Based on these outstanding scientific achievements, I chose to firmly support Professor Ji and ShanghaiTech University in translating these results into practical applications. After identifying highly capable industrial professionals from leading U.S. gene-editing biotechnology companies who shared a strong willingness and determination to return to China and co-found a venture with Professor Ji, the Med-Fine Capital team made a swift decision to invest and jointly establish CASTALYSIS BIOSCIENCE. Committed to becoming a globally influential Chinese company in the field of in vivo gene editing, we are honored to have partnered with CASTALYSIS BIOSCIENCE since its inception and will continue to steadfastly support and facilitate its success.”

Med-Fine Health Fund focuses on investments in the pharmaceutical, healthcare, and life sciences sectors, with offices in Shanghai, Beijing, and Shenzhen. The management team boasts a broad international perspective, deep industry background, extensive sector resources, and professional investment expertise. The firm currently manages four RMB-denominated funds and two USD-denominated funds. Emphasizing "early-stage value discovery and sector opportunity identification," the fund targets investment opportunities in biopharmaceuticals, medical devices and diagnostics, digital health, and health technology. To date, it has completed investments in more than 60 pharmaceutical and healthcare companies, including Hanyu Medical, TianGuangShi, ImmuneOnco, Zhenrong Pharma, LinkTherapeutics, Chengyi Biologics, PhenoGene, HeartEngine Medical, Libang Pharmaceutical, Anray Bio, Saifu Pharma, Anson Technology, Acupulse, Shuimu Medical, Anlinko Bio, and CASTALYSIS BIOSCIENCE.

Guided by the vision of “Shaping the Horizon of Life and Health” and driven by the mission to “Leverage Capital to Foster Innovative Development in the Healthcare Industry,” Med-Fine Capital adheres to the core values of “Customer First, Talent Excellence, Quality Leadership, and Trustworthy Returns.” By integrating “Decentralized Investment” with “Systematic Operations,” Med-Fine Capital is committed to becoming an open, platform-based, highly competitive, and internationally renowned professional investment institution.