Over hundreds of years, the fight against bacteria has been like an arms race, and the immediate development of safe and effective vaccines is a magic weapon for humans to defeat bacteria. In 2017, the WHO released a list of 12 deadly superbugs, with Staphylococcus Aureus (S. aureus for short) ranking first among drug-resistant bacteria. Currently, there is no vaccine against S. aureus internationally yet.

However, this situation may be broken by a Chinese bio-pharmaceutical company. “Up to today, we should be the only company that is currently conducting clinical trials for Staphylococcus Aureus Vaccine in Phase III in Chin.” Fan Fan, Vice Chairman and one of the actual controllers of OLYMVAX, said.

OLYMVAX was established in 2009 and listed on the Science and Technology Innovation Board in 2021. So far, it has three products launched, 1 product under production and registration, and 1 product in Phase III clinical study. Among them, tetanus vaccine is the first product marketed and sold by the Company, with a domestic market share of nearly 90%. In addition, if the Staphylococcus Aureus Vaccine, which has entered clinical phase III, is successfully launched, it is expected to fill the gap in the world and resolve the problem of super drug-resistant bacteria.

Recently, the “Times Parlor ? Dialogue with China's Heavyweights in Science and Technology Innovation” reporter team of the Securities Times visited OLYMVAX and had an interview with Fan Fan to understand the development history of OLYMVAX.

Staphylococcus Aureus Vaccine

will fill the gap in the world

S. aureus is the pathogenic bacteria with the highest infection rate in ICU wards and traumas in the world, and is ranked among the top drug-resistant bacteria. Large pharmaceutical companies around the world, such as Merck, Pfizer and GlaxoSmithKline, have conducted human clinical studies on Staphylococcus aureus vaccine. However, due to issues such as vaccine components, adjuvants and indication selection, no Staphylococcus aureus vaccine has been marketed so far.

The role of the Staphylococcus Aureus Vaccine is to address the global problem of drug-resistant bacteria caused by antibiotic overuse. At present, the main method against Staphylococcus aureus infections in patients is to inject antibiotics, which will bring about drug-resistant bacteria and superbugs.

“We have collaborated with the Army Medical University in the development of Staphylococcus aureus vaccine since 2011. The Army Medical University had more than 10 years of research and development prior to working with us. Equivalently, we continue to study this vaccine and commercialized it.” Ms. Fan Fan said. Staphylococcus Aureus Vaccine is rated as Class 1.1 original new drug in China. Since the approval of the clinical trial in 2015, this vaccine development project has taken 7 years to complete the Phase I and II human clinical trials with 666 subjects. The results show that the Recombinant Staphylococcus Aureus Vaccine has good vaccination safety and immunogenicity in the target population of 18-70 years old in China. The data from preclinical studies and Phase I clinical studies have been published in the international journal Vaccine in 2020.

Ms. Fan Fan said that if the clinical trial goes with a swing, the Staphylococcus Aureus Vaccine is expected to be applied for market in 2025. Even more noteworthy is that there are currently no Staphylococcus Aureus Vaccines successfully approved for marketing in the world, and only OLYMVAX has entered the clinical trials in China.

“This vaccine is designed for the whole population, that is, all healthy people are immune to Staphylococcus aureus infection, although orthopedic patients are enrolled for the clinical trials. After its launch, the indications for the Staphylococcus Aureus Vaccine are expected to expand from orthopedic surgery to other indications for nosocomial infection, and it can be applied to the full range of nosocomial infection scenarios.” Ms. Fan Fan analyzed.

Ms. Fan Fan said that the Staphylococcus Aureus Vaccine has a broad application prospect. For example, there are about one million of orthopedic surgeries in China every year. If the bridging technology is further developed, the number of hospitalized surgical patients in Chinese hospitals will exceed 50 million per year, and the current infection rate of Staphylococcus aureus in surgical patients is 5% to 8%.

The Phase III clinical study of Staphylococcus Aureus Vaccine was officially launched in June 2022 and performed in more than 50 clinical study centers with 6,000 subjects. However, the project remains uncertain, given that there is no success story worldwide.

“There is a saying of “three tens” in our industry. To be specific, it may spend RMB 1 billion and 10 years to develop an original new drug, but the success probability will be less than 10%. The Staphylococcus Aureus Vaccine has been shown to be safe and partially effective from the data of Phase I and II, but the sample size at that time was relatively small. Now we need to expand it to 6,000 people to demonstrate the protective efficiency in a larger sample size. We are also looking forward to the data of Phase III.” Ms.Fan Fan admitted.

Tetanus vaccine provides cash flow.

As is well known, vaccines have high technical, financial, and policy barriers; on the other hand, the vaccine industry is also a high-risk industry, with high capital consumption and a long development cycle for vaccine products. How to find a balance between the R&D arrangement and the survival and development of the company is a great challenge that troubles many vaccine companies.

The lucky thing for OLYMVAX is that it has found its “cash cow” in early stage.

OLYMVAX was approved to launch its Tetanus Vaccine, Adsorbed in 2017, and it became the only private enterprise in this field. At that time, the domestic tetanus vaccine market was only about 300,000 to 500,000 doses a year, and the prevention against tetanus was mainly realized by passive immunization.

However, passive immunosuppressant is just a temporary palliative. The adsorbed tetanus vaccine has a longer effect and a lower allergy rate. The protection period is 5 to 10 years for tetanus vaccine, while only 10 to 28 days for passive immunosuppressant which cannot completely protect the tetanus bacteria in the patient during incubation period.

OLYMVAX has started popularizing the knowledge of tetanus vaccine. “We organized the information into documents and reached a consensus with many clinical experts. The experts agreed to develop a clinical diagnosis and treatment standard for promotion.”

In 2019, the National Health Commission issued the Practice for Diagnosis and Treatment of Non-neonatal Tetanus (2019 edition), which clearly required that the prevention of non-neonatal tetanus should be dominated by vaccines and supplemented by passive immunosuppressant, which changes the market structure of tetanus prevention.

OLYMVAX sales data indicated that the Company's revenue from Tetanus Vaccine, Adsorbed grew rapidly from RMB 64.4485 million in 2018 to RMB 393 million in 2021, and its gross profit rate remained more than 95% for many years, which was comparable to that of Maotai. According to the Company’s Preliminary Earnings Estimate in 2022, the Company achieved revenue of RMB 547 million in 2022. Based on the historical proportion of tetanus vaccine in the Company’s revenue, the sales of tetanus vaccine may reach about RMB 400 million in 2022. From the perspective of market share, OLYMVAX has always accounted for over 80% and is in the absolute leading position.

However, other competitors are also coming to this premium investment sector. Hualan Bio announced on February 27 evening that its holding subsidiary Hualan Biological Vaccine Co., Ltd. was recently approved by the National Medical Products Administration to issue the adsorbed tetanus vaccine.

AC-Hib triple vaccine

May be the next flagship product?

On February 14, OLYMVAX announced that its application for AC-Hib combined vaccine marketing was accepted. AC-Hib triple vaccine is expected to be approved for marketing in the second half of 2023.

AC-Hib vaccine can be used to prevent meningitis, pneumonia, septicemia, cellulitis, arthritis, epiglottitis and other infectious diseases caused by Group A and Group C meningococcus and Haemophilus influenzae type b in children aged 2 months to 5 years. Compared with the single vaccine, combined vaccine can effectively reduce the number of vaccinations in children and improve their compliance.

At present, there is no AC-Hib triple vaccine approved for lot release in China, and the Phase III clinical trials of AC-Hib triple vaccine have been completed by Zhifei Biological and OLYMVAX.

Fan Fan stated that the AC-Hib combined vaccine was sold in the Chinese market from 2017 to 2019, but it is currently missing from the market due to various reasons. “We can speculate that AC-Hib triple vaccine may probably have a market size of more than RMB 1 billion a year according to the lot release data from 2017 to 2019.”

In addition to continuous deep research on bacterial vaccines, OLYMVAX is also gradually exploring the viral vaccines. OLYMVAX Research Institute was established at the end of last year, with Fan Fan serving as the President. The Institute mainly focuses on the research of bacterial vaccines, viral vaccines and nucleic acid vaccines. “As a vaccine research and production enterprise, we think that virus research is essential, so we have started to reserve our research and development resources in the field of viral vaccines since last year.” Ms. Fan Fan said.

The Company has practiced a R&D mode of “laying equal stress on independent development and joint development”, and set up an innovative vaccine research team with independent intellectual property rights. During the 14 years since its establishment, 3 vaccines have been launched, 1 product is under production and registration, and 1 product is in Phase III clinical study...Such achievements are a source of pride for OLYMVAX. With mature product supply cash flow, abundant and orderly tiered products, and future-oriented cutting-edge arrangement, “OLYMVAX will become a domestically renowned and internationally leading original vaccine enterprise in the future.” Fan Fan envisioned.