SW-Biopharma Completes Nearly RMB 100 Million Series A Funding, Pioneering Domestic mRNA Therapeutics Platform
Can Cancer Patients Truly Achieve Personalized Treatment? The ability to access medications that are effective for each individual has always been a concern for every patient and represents the ultimate goal of cancer therapy. Personalized mRNA cancer vaccines, leveraging the latest mRNA technology and targeting tumor neoantigens, offer the most promising solution to this challenge.
Leading mRNA pharmaceutical companies abroad have already attracted significant capital interest. Moderna raised $600 million in its late-2018 IPO, setting a record for biotechnology company IPO fundraising; Germany’s BioNTech secured up to $325 million in Series B financing in July 2019. The fervent pursuit of the mRNA industry and personalized cancer therapy by venture capitalists and large pharmaceutical companies stems from their optimism about the sector’s immense future potential and the revolutionary transformation that mRNA drugs will bring to oncology treatment. In China, Stemirna Therapeutics is leveraging its proprietary platform technology to gain a foothold and emerge as a notable player in this rapidly burgeoning industry.
Stemirna Therapeutics completed a nearly RMB 100 million Series A financing round in July 2019. Investors included Zhangjiang Torch Venture Capital, Zhuhai Longmen No. 3 Fund, Jiuyou Wisdom, Yitai Jiuyou, and Fanghua Investment. Dragon Rock Investment, the angel-round investor, made an additional investment in this round, while Probe Capital served as the financial advisor. The proceeds from this round will be used to construct Stemirna’s mRNA drug GMP manufacturing center, conduct clinical trials at three hospitals, and submit Investigational New Drug (IND) applications for its personalized cancer vaccine projects. Stemirna will simultaneously advance early-stage research on its subsequent pipeline candidates.
The three founders of Stemirna Therapeutics developed a strong interest in the mRNA field as early as 2011. Professor Tang Dingguo is a leading authority in tumor stem cells and miRNA; Dr. Li Hangwen has dedicated many years to cancer immunology research; and Professor Shen Haifa, a top global expert in drug delivery, brings eight years of industry experience. The convergence of their expertise prompted Professor Shen to initiate experimental research on mRNA delivery at an early stage, when Moderna was just getting started and BioNTech remained largely unknown.
Dr. Li Hangwen, Founder of Stemirna Therapeutics
In 2015, preliminary animal trial data for the mRNA cancer vaccine from Professor Shen’s laboratory were released, with promising results in mouse studies. The three founders were firmly convinced of the market potential for mRNA technology and recognized that domestic mRNA technology platforms were virtually nonexistent. They promptly proceeded to establish Stemirna Therapeutics. In May 2016, Stemirna Therapeutics was officially inaugurated in Zhangjiang, Shanghai. In July 2017, following negotiations with Houston Methodist Hospital affiliated with Cornell University, Stemirna Therapeutics formally secured the exclusive global license for patents related to the mRNA delivery technology invented by Professor Shen Haifa.
Stemirna’s mRNA vaccine delivers in vitro-synthesized mRNA fragments encoding neoantigens, encapsulated in nanomaterials, into human cells. Subsequent translation within the body leads to the expression of patient-specific neoantigens, which trigger an endogenous immune response, enabling the immune system to recognize and eliminate tumor cells bearing these neoantigens.
The emergence of mRNA cancer vaccines is the culmination of scientific research advancements. In recent years, research into neoantigens has identified the most suitable developmental direction for mRNA cancer vaccines. Neoantigens are abnormal proteins generated by genetic mutations in cancer cells that can be recognized by the immune system, and they represent one of the key focal points in the field of tumor immunology today. Each cancer patient exhibits subtle differences in their mutation profiles, resulting in patient-specific neoantigens.
In addition to the mRNA approach, the development of therapeutic vaccines targeting neoantigens also includes a peptide-based strategy, which involves directly using synthetically produced neoantigen peptides in vitro to elicit an immune response. However, mRNA vaccines offer greater potential advantages over peptide vaccines in terms of efficacy, safety, breadth of coverage, and cost. Consequently, leading global companies in the therapeutic vaccine sector, such as Moderna, CureVac, and BioNTech, are primarily focusing their R&D efforts on mRNA vaccines.
Compared with peptides, mRNA has significant advantages in preparation. Some technical challenges of peptide vaccines, such as high difficulty in in vitro synthesis, water solubility issues, high production costs, and long development cycles, can all be addressed by mRNA vaccines. In addition, mRNA cancer vaccines do not require HLA typing, and the antigens expressed in vivo lack direct immunogenicity, among other advantages. It is widely believed in the industry that the mRNA drug platform has the potential to become a disruptive, next-generation product.
Because naked mRNA is highly susceptible to degradation upon direct entry into the body, the core barrier in the field of mRNA vaccines lies in developing effective and safe delivery systems. The Core-Shell mRNA delivery system invented by Professor Shen Haifa effectively addresses key challenges in the research and development of mRNA vaccines.
Most delivery systems employ single-layer liposomal membranes to encapsulate their cargo, whereas the Core-Shell platform advances this architecture from a single-layer to a double-layer structure. The encapsulated carriers enter cells via endocytosis, and the bilayer membrane provides enhanced protection for mRNA integrity prior to its functional activity. The Core-Shell platform also demonstrates high transfection efficiency in dendritic cells (DCs). As the most potent antigen-presenting cells, DCs efficiently activate the immune system through the DC–lymph node–antigen presentation pathway. High DC transfection efficiency indicates that mRNA vaccines formulated using the Core-Shell platform can elicit stronger, more efficient, and highly specific immune responses.
Stemirna Therapeutics’ first product pipeline, SM-Neo-Vac-1, is a personalized neoantigen mRNA vaccine designed for patients with advanced digestive system tumors. This product predicts patient-specific neoantigens through whole-exome sequencing and transcriptome sequencing, enabling the customization of tumor vaccines tailored to each individual patient. The tumor vaccine is administered via subcutaneous injection, ensuring safe delivery into the patient’s body to initiate subsequent immune responses. Stemirna Therapeutics plans to submit Investigational New Drug (IND) applications for its products targeting gastrointestinal tumors, lung cancer, and melanoma in 2020.
Although Stemirna Therapeutics’ first product is a personalized cancer vaccine, the company is committed to building itself into a drug R&D platform enterprise based on its two core platforms: nano-delivery and mRNA synthesis. “The mRNA cancer vaccine is merely our inaugural product; we are also actively expanding into the field of infectious diseases, such as influenza and MERS-CoV. Meanwhile, we will maintain our strategic presence in oncology immunotherapy, antibodies, rare diseases, and gene therapy. In addition to treatment, prevention will be another key area of focus,” said Li Hangwen, CEO of Stemirna Therapeutics.
After securing patent authorization, Stemirna Therapeutics quickly obtained its first round of investment. In September 2017, the company received angel-round funding from Longpan Investment and Jinggong Hongyuan. With this capital in hand, Stemirna immediately commenced the construction of its R&D center. In May 2018, a 600-square-meter R&D center and GMP-compliant production facilities were put into operation, granting Stemirna initial capabilities in CMC for pharmaceutical formulations and mRNA synthesis.
Establishing an in-house GMP-compliant mRNA production and synthesis system was both a necessary compromise and an inevitable choice for Stemirna Therapeutics. When Li Hangwen first returned to China, he evaluated several leading domestic CRO/CMO companies. At that time, no local suppliers were capable of providing IVT mRNA synthesis, forcing Stemirna to source its required mRNA from the United States. However, importing from abroad entailed not only high shipping costs and complex customs procedures but also unreliable lead times. Furthermore, the high-end nano-formulations based on Stemirna’s Core-Shell platform had to be manufactured in-house, which necessarily required the company to establish its own GMP-compliant production facilities.
In 2019, Stemirna Therapeutics began constructing a new GMP manufacturing center for mRNA-based therapeutics. “Although the process of building our own facility was challenging, we now feel it was well worth the effort. We currently operate two core platforms: an mRNA synthesis platform and a nanoparticle drug delivery platform. This allows us to maintain complete control over the entire production process. With this foundation, we have greater confidence, and our future development will naturally accelerate,” said Li Hangwen.
In addition to advancing the construction of its production lines, Stemirna Therapeutics’ next phase of work will focus on improving the efficiency of its product process systems. “Currently, the production cycle for personalized cancer vaccines at Moderna, a global leader in mRNA therapeutics, is approximately 4–6 weeks. Although we can already achieve a 6-week turnaround, we aim to further enhance our efficiency. The new GMP facility is also designed to meet our demands for faster delivery and higher quality,” said Li Hangwen.
Stemirna Therapeutics has established collaborative partnerships with multiple Grade A tertiary hospitals in China, including Shanghai Changhai Hospital, Shanghai Dongfang Hospital, the First Affiliated Hospital of Zhengzhou University, and Ruijin Hospital, and has initiated several preclinical and clinical research studies. The clinical trials at Shanghai Changhai Hospital, Shanghai Dongfang Hospital, and the First Affiliated Hospital of Zhengzhou University have passed ethical review and completed patient enrollment. Preliminary clinical data to date indicate that treated patients have demonstrated favorable safety profiles and immune responses.
“Late last year was probably the toughest period, but we made it through.” Like all entrepreneurs, Li Hangwen has experienced numerous ups and downs over the past three years. In this season that appears to be a “capital winter,” Stemirna Therapeutics has garnered support from multiple institutions by leveraging its proprietary platform technologies. With clinical trials progressing smoothly, GMP facilities being steadily developed, and an Investigational New Drug (IND) application imminent, 2019 is poised to be a year of accelerated growth for Stemirna Therapeutics. In the competitive landscape of mRNA vaccines, Stemirna Therapeutics, having mastered core competencies, has secured a leading position in China’s mRNA sector and is well-positioned to compete with top global players in the future.