Legend Capital, Temasek, Sequoia Back China's Leading HPV Vaccine Developer RecBio in Hong Kong IPO Bid

Recently, Jiangsu Ruike Biotech Co., Ltd. submitted a listing application to the Hong Kong Stock Exchange, with Morgan Stanley, CMB International, and CITIC Securities serving as its joint sponsors. If Ruike Biotech successfully lists, it is poised to become the first HPV vaccine company on the Hong Kong stock market.

In China, HPV vaccines, particularly the 9-valent HPV vaccine, have long faced a shortage characterized by extreme difficulty in securing doses. Statistics show that three imported HPV vaccines are currently approved for marketing in China: GlaxoSmithKline’s bivalent vaccine and Merck & Co.’s quadrivalent and 9-valent vaccines. Notably, the 9-valent HPV vaccine was previously listed as an urgently needed new drug already marketed abroad and was included in the priority review and approval program to expedite its regulatory clearance.

However, imported vaccines largely failed to meet domestic market demand. The approval and launch of Wantai Bio’s bivalent HPV vaccine significantly alleviated the issues of high prices and limited supply. This not only marked the end of China’s reliance on imported HPV vaccines but also highlighted the rising prominence of domestically produced HPV vaccines.

Currently, numerous companies, including Beijing Biological Products Institute, Kangtai Weishi, Anbaisheng Biotech, Shanghai Bowei Biotech, Jiangsu Ruike Biotech, and Zhejiang Pukang, are focusing on the HPV vaccine sector, a market valued at tens of billions. Among them, Jiangsu Ruike Biotech has stood out through nearly a decade of development, leveraging its accumulated strengths to embark on its path toward an IPO on the Hong Kong Stock Exchange.

Ruike Biotech is an innovative vaccine company founded in 2012, dedicated to the research, development, and commercialization of safer and more effective innovative vaccines. The company has established three major technology platforms: novel adjuvants, protein engineering, and immune evaluation. It is one of the few companies globally capable of developing novel human adjuvants comparable to those approved by the U.S. Food and Drug Administration (FDA). Leveraging its robust R&D capabilities, Ruike Biotech has built a strong portfolio of 12 candidate vaccines. Its core product, REC603—a recombinant nonavalent HPV vaccine—is currently in Phase III clinical trials.

Since its inception, Jiangsu Ruike Biotech Co., Ltd. has been highly sought after by leading investment institutions:

According to the prospectus, since its establishment, Jiangsu Ruike Biotech Co., Ltd. completed its Series A, Series B, Series B+, and Series C financing rounds in January 2019, October 2020, March 2021, and May 2021, respectively. The investors included a number of well-known institutions such as Legend Capital, Temasek, Oriental Fortune Capital, Sequoia Capital China, Qingchi Capital, CMB International, and CDH Investments.

Having secured over RMB 2 billion in financing within just two and a half years, the development trajectory of Jiangsu Ruike Biotech Co., Ltd. not only demonstrates its leading technological and R&D capabilities within the industry, but also signals significant growth potential for its future.

Vaccines consist of two components: antigens and adjuvants. Antigens are characteristic proteins of pathogens that serve as templates for immune system recognition, while adjuvants are used to activate the immune system and canAntigen binding facilitates antigen presentation and enhances the immune response.Typically, immunity induced by antigens alone is limited; therefore, adjuvants are required to enhance vaccine efficacy.

By convention, only aluminum adjuvants have been widely used in human vaccines. However, since the early 21st century, novel adjuvants have gradually gained widespread application in the vaccine industry, enabling the development of vaccine products that elicit stronger and broader immune responses. According to a Frost & Sullivan report, apart from aluminum adjuvants, only five novel adjuvants—namely AS01, AS03, AS04, CpG 1018, and MF59—have been used in FDA-approved human vaccines, with their relevant components having been in the public domain for over two decades.

Global Categories of Novel Adjuvants (Source: Prospectus)

Novel adjuvants are typically difficult to manufacture, requiring advanced production technologies and subject to stricter regulatory standards, which limits production capabilities to only a few companies. Currently, the vast majority of vaccine manufacturers lack the capacity for commercial-scale production of novel adjuvants and cannot outsource this process to Contract Development and Manufacturing Organizations (CDMOs). Consequently, they must partner with companies such as GSK to secure adjuvant supplies. However, this reliance can directly impact vaccine supply chains and cost control, particularly given the current demand for COVID-19 vaccines in the hundreds of millions of doses, which poses significant challenges for external adjuvant sourcing. Adjuvant development is increasingly becoming a critical "bottleneck" technology for China’s vaccine industry.

Reco Biotech’s journey to tackle the challenges of novel adjuvants began in the early stages of its founding, and after nearly a decade of development and optimization,Ruike Biotech has become one of the few companies capable of developing adjuvants that benchmark against all such adjuvants approved by the U.S. Food and Drug Administration (FDA).

According to the prospectus, the company has developed two new adjuvanted HPV vaccines—namely, the quadrivalent vaccine REC604a and the nonavalent vaccine REC604b—using a proprietary novel adjuvant benchmarked against AS04. This approach significantly enhances immunogenicity and elicits cross-protective immunity, potentially reducing the number of required doses. The performance-enhancing effects of this novel adjuvant are also evident in the company’s recombinant COVID-19 vaccine, ReCOV, and its recombinant zoster vaccine, REC610. Leveraging its capability for independent development of novel adjuvants, Jiangsu Ruike Biotech Co., Ltd. has eliminated dependence on any specific adjuvant supplier and positioned itself to discover and apply novel adjuvants in next-generation vaccine candidates.

Favored by capital and boasting advanced R&D capabilities, Jiangsu Ruike Biotech Co., Ltd. has significantly expanded and strengthened its product pipeline, establishing a portfolio of 12 vaccine candidates covering a broad spectrum of diseases, including cervical cancer, COVID-19, adult tuberculosis, herpes zoster, hand-foot-and-mouth disease, and influenza. Among these, the HPV vaccine is its core product. According to the prospectus, five of the company’s 12 product pipelines are dedicated to HPV vaccines, aiming to address highly differentiated market demands through an “HPV Vaccine Family.”

Reco Biotech’s Product Pipeline (Image source: Prospectus)

Currently, Jiangsu Ruike Biotech Co., Ltd. is promoting its HPV vaccine portfolio as a “combination strategy,”Clinical trials are being advanced for three primary vaccine candidates, including a recombinant nonavalent HPV vaccine, REC603, and two recombinant bivalent vaccines, REC601 and REC602.This strategic layout enables the company to seize a first-mover advantage in the vaccine market, leveraging its strengths in rapid deployment, high quality, and comprehensive population coverage.

According to the prospectus, Recombinant Biotech's core productsNine-valent HPV Vaccine REC603The trial has entered Phase III, and all subjects have completed enrollment.Expected to become the first domestically produced nine-valent HPV vaccine to be marketed in China, it is projected to reach the primary endpoints of clinical studies and submit a marketing application in 2025.It demonstrated favorable safety and immunogenicity in its Phase I clinical trials, while achieving high-yield and stable expression of HPV virus-like particles, thereby making it more suitable for commercial-scale production.

The other two bivalent HPV vaccine candidates are currently in Phase I clinical trials. Upon completion of the Phase I clinical trials for REC601 and REC602, Jiangsu Ruike Biotech Co., Ltd. will initiate the next phase of clinical trials and plans to submit Biologics License Applications (BLAs) for these bivalent HPV vaccines in 2025.

In addition to the HPV vaccine that has entered clinical trials, Jiangsu Ruike Biotech Co., Ltd. has embarked on a new journey——Development of Two Second-Generation HPV Vaccines, Including a Quadrivalent Candidate Vaccine (REC604a) and a Nonavalent Candidate Vaccine (REC604b)According to the prospectus, Recbio will utilize a novel adjuvant independently developed to benchmark against AS04, with the aim of reducing the number of doses required. Based on existing research, clinical trials have shown that Cervarix, which uses GSK’s AS04 adjuvant, induces higher neutralizing antibody titers and demonstrates stronger cross-protective efficacy compared to Merck’s Gardasil. This suggests that this novel adjuvant can enhance the immunogenicity of HPV vaccines. Recbio expects to submit Investigational New Drug (IND) applications for REC604a and REC604b in 2022 and 2023, respectively.

To align vaccine production capacity with R&D capabilities and meet substantial market demand, Jiangsu Ruike Biotech Co., Ltd. has invested heavily in constructing manufacturing facilities with sufficient production capacity. Currently, the company is building an HPV vaccine production base in Taizhou, Jiangsu Province. The first phase of this facility is expected to be completed by the end of 2022, with a designed annual production capacity of 5 million doses of nine-valent HPV vaccine or 30 million doses of bivalent HPV vaccine.

Thus, the dual focus on technology and production capacity is expected to position Jiangsu Ruike Biotech Co., Ltd. as a leader in the domestic HPV vaccine sector.

In addition to its HPV vaccine, Jiangsu Ruike Biotech Co., Ltd. is accelerating the development of vaccines for other disease areas, enhancing its competitive edge through a portfolio or combination of products rather than relying on a single offering. The company’s other vaccine candidates in development are as follows:

ReCOV is a recombinant protein-based COVID-19 vaccine that primarily utilizes BFA03, a novel adjuvant benchmarked against AS03. Phase I clinical trials for ReCOV were initiated in New Zealand in June 2021, with initial partial unblinded data obtained in October 2021. Based on the primary safety and immunogenicity data from the Phase I trial, along with partial unblinded efficacy data, ReCOV received approval from the Philippine FDA in January 2022 to conduct global Phase II/III clinical trials. Currently, Jiangsu Ruike Biotech Co., Ltd. plans to submit an Emergency Use Authorization (EUA) application in 2022.

REC610 is currently in the IND application stage. Approximately 2.5 million adults in China are infected with the varicella-zoster virus annually, and nearly all Chinese adults aged 50 and above carry the virus in a latent state. According to existing clinical studies, GSK’s adjuvanted recombinant protein vaccine, Shingrix, is the only approved shingles vaccine in China, demonstrating superior efficacy compared to Merck’s Zostavax. REC610 utilizes a recombinant protein technology similar to that of Shingrix, and an IND application for REC610 was planned for submission in 2022.

Currently, Recombio is developing two adult tuberculosis vaccine candidates (namely REC607 and REC606), one of which is a recombinant protein vaccine formulated with the novel adjuvant BFA01 (benchmarked against AS01). In collaboration with the Shanghai Public Health Clinical Center, Recombio is developing a Sendai virus vector-based candidate vaccine featuring a novel immunogenicity design. This project was designated as a National Science and Technology Major Project in 2018, and the company currently plans to submit Investigational New Drug (IND) applications for these two vaccine candidates in 2023.

Nowadays, the COVID-19 pandemic has become the primary driver for influenza vaccination. In a head-to-head trial comparing Sanofi’s Flublok vaccine with GSK’s Fluarix vaccine, results showed that subjects vaccinated with Flublok had a 30% lower probability of developing influenza-like illness compared to those vaccinated with Fluarix. Recbio Biotech has independently developed REC617, a novel adjuvant using an approach similar to that of Flublok, which can further enhance the tolerability, immunogenicity, duration of protection, cross-protection capability, and production scalability of influenza vaccines.

Hand, foot, and mouth disease (HFMD) is a common contagious viral infection in children. The viruses commonly causing HFMD include EV71, CA16, CA10, and CA6, which account for more than 90% of HFMD cases in China. Currently, the inactivated EV71 vaccine is the only approved HFMD vaccine globally and in China; therefore, there is significant demand for multivalent vaccines. The recombinant quadrivalent HFMD vaccine developed by Recombio Biotech based on protein engineering technology can enhance serotype coverage and vaccine efficacy against EV71, CA16, CA10, and CA6.

For the aforementioned vaccine products, Recombinant Biotech completed the construction of its GMP-compliant production facility for ReCOV in November 2021. This facility, with a total gross floor area of approximately 17,000 square meters, can also be used to produce the recombinant zoster vaccine and has the potential to support an annual production capacity of 300 million doses of ReCOV.

In China, the HPV vaccine market holds substantial potential and is expected to grow rapidly in the coming years. According to a Frost & Sullivan report, the overall HPV vaccination rate in China remains low, at less than 1% of the total population. Even when accounting for the projected increase in HPV vaccination rates,By 2025, it is estimated that 233.9 million women aged 9 to 45 in China will remain unvaccinated against HPV; assuming a three-dose regimen per person, an additional 701.7 million doses may be required.

From the perspective of China's HPV vaccine market,Since the first approval of HPV vaccines in China in 2017, the market size for HPV vaccines grew to RMB 13.5 billion in 2020 and is projected to reach RMB 69 billion by 2030., with a compound annual growth rate (CAGR) of 17.7% from 2020 to 2030.

According to the prospectus of Jiangsu Ruike Biotech Co., Ltd., the 9-valent HPV vaccine is expected to hold the largest market share within the overall HPV vaccine market by 2030. Furthermore, as the 2-valent HPV vaccine is generally more affordable and accessible to a larger population with limited financial means, the market for 2-valent HPV vaccines is projected to experience rapid growth.

Forecast of the Output Value of China’s HPV Vaccine Market (Source: Prospectus)

The substantial market demand and rapidly accumulating market growth represent the development potential of Jiangsu Ruike Biotech Co., Ltd., while policy support will help the company go further.

November 2020,The World Health Organization announced the Global Strategy to Accelerate the Elimination of Cervical Cancer, with the goal of achieving 90% HPV vaccination coverage among girls under the age of 15 by 2030.As of the end of 2020, 110 countries had included HPV vaccines in their national routine immunization programs, with an additional 10 countries planning to introduce them by the end of 2021.

December 2020,The Department of Maternal and Child Health of China’s National Health Commission Has Stated That It Will Fully Support the Strategy to Accelerate the Elimination of Cervical Cancer. Furthermore, members of the National Committee of the Chinese People's Political Consultative Conference proposed on May 21, 2020, that HPV vaccines be included in the National Immunization Program. This proposal indicates that girls aged 9 to 14 would receive the bivalent HPV vaccine free of charge. To date,Multiple provinces and municipalities, including Inner Mongolia, Fujian, Shandong, and Guangdong, have begun implementing policies for free HPV vaccination, incorporating the HPV vaccine into their local immunization programs.

A series of policies from the Chinese government, combined with the fact that the bivalent HPV vaccine typically provides protection against approximately 70% of cervical cancer cases globally, suggest that the HPV vaccine is likely to be included in China’s National Immunization Program. This development could enable Jiangsu Ruike Biotech Co., Ltd. to achieve a qualitative transformation in its corporate growth.

Apart from the HPV vaccine market, China’s vaccine market is expected to experience rapid growth. According to Frost & Sullivan, measured by output value, the market size has increased from RMB 27.1 billion in 2016 to RMB 75.3 billion in 2020, representing a compound annual growth rate (CAGR) of 29.1%. It is projected to reach RMB 333.3 billion by 2030, with a CAGR of 16.0% from 2020 to 2030. This expansion in market size will provide strong growth momentum for Recomb Biotech’s other vaccine products.

Forecast of China’s Vaccine Market Output Value (Source: Prospectus)

According to the prospectus, Jiangsu Ruike Biotech Co., Ltd. generated no revenue from its core business in 2019, 2020, and the first nine months of 2021. Its R&D expenses for these periods were RMB 63 million, RMB 131 million, and RMB 371 million, respectively, while net losses amounted to RMB 138 million, RMB 179 million, and RMB 520 million, respectively. Nevertheless, the fact that its core products had not yet been launched and the company had incurred consecutive annual losses did not dampen capital markets’ enthusiasm for Jiangsu Ruike Biotech.

Reco Biotech’s Financial Revenue (Source: Prospectus)

In the future, Recbio’s innovative vaccine products across numerous disease areas will inject fresh revolutionary momentum into the development of the vaccine sector. We look forward to good news regarding the market launch of Recbio’s products.