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To control the spread of various mutant strains and the COVID-19 pandemic, countries worldwide are actively carrying out large-scale booster vaccinations to consolidate the "first line of defense" against the epidemic. Many countries, including the US and UK, have taken the lead in promoting sequential booster immunization strategies using different technological approaches. On February 19, the State Council's Joint Prevention and Control Mechanism announced the deployment of sequential booster immunization, marking the beginning of heterologous booster vaccination in China.

Recently, Lizhu Group (000513.SZ) disclosed that its subsidiary, Lizhu Monoclonal Antibody Biotechnology Co., Ltd. ("Lizhu Monoclonal Antibody"), has completed the interim primary data analysis of the Phase III clinical trial of its "recombinant novel coronavirus fusion protein vaccine" (V-01) for sequential booster vaccination and obtained key data.

The results of the interim analysis showed that the absolute protective efficacy of V-01 after sequential boosting reached 61.35%, meeting WHO standards, and demonstrating significant superiority. V-01 sequential boosting also showed good protective efficacy against the Omicron variant. Furthermore, in the Phase III clinical trial of sequential boosting, group studies of high-risk populations showed that V-01 had a protective efficacy of 71.38% in individuals with underlying diseases.

This is the world's first COVID-19 vaccine to use sequential boosting based on an inactivated vaccine and obtain rigorous Phase III clinical data.

It is understood that Lizhu Group has submitted an application to the National Medical Products Administration for the listing of V-01 as a sequential booster shot. Work on emergency use authorization (EUA) or market applications and WHO certification in several overseas countries and regions is also underway. This vaccine is expected to provide more flexible and scientific candidate options for sequential booster immunization.

Sequential Booster Absolute Protective Efficacy Reaches 61.35%, Showing Significant Superiority

As one of the five major technological routes for COVID-19 vaccines, recombinant protein vaccines have attracted considerable attention due to their advantages, including low biosafety requirements for production facilities, relatively simple mass production, undemanding storage and delivery conditions, high purity, and good safety.

In July 2020, Lizhu Group launched a project to develop this innovative recombinant protein COVID-19 vaccine with independent intellectual property rights in collaboration with the Institute of Biophysics, Chinese Academy of Sciences. Eight months later, V-01 obtained clinical trial approval and entered clinical trials.

Preliminary analysis of Phase I clinical trials released in June 2021 showed that V-01 had a good safety profile and could rapidly induce a strong immune response. Phase II clinical data for two doses of V-01 were published in the Chinese Medical Journal in July 2021, further confirming its good safety and immunogenicity.

It is understood that the Phase II clinical trial of V-01 in individuals aged 18 and above included 880 subjects (young adults and older adults in a 1:1 ratio). The incidence of adverse events related to the trial vaccine was low during the study, and overall reactogenicity was almost non-existent or mild. In terms of immunogenicity, 14 days after two doses of the vaccine were administered according to a 0, 21-day schedule, all vaccinated individuals in the vaccine group produced high-titer antibodies, and the seroconversion rate of neutralizing antibodies in the target dose vaccine group was over 97%.

The excellent safety and immunogenicity of V-01 are based on its innovative and unique molecular structure design. The V-01 molecule consists of four parts: interferon, Pan epitope, RBD dimer, and Fc fusion protein. The inclusion of human interferon as a biological adjuvant in the antigen structure significantly enhances the level of virus-neutralizing antibodies and produces an effective cellular response.

With the global prevalence of Omicron and the gradual rollout of booster immunization strategies, Lizhu launched Phase III clinical trials of sequential booster immunization in Pakistan and Malaysia in October 2021. It is noteworthy that, unlike most current sequential booster efficacy studies, which are investigator-initiated clinical trials (IITs), the V-01 program is the world's first international multicenter, randomized, double-blind Phase III clinical trial (IST) to study sequential booster protection.

This sequential booster program is designed for sequential boosting based on two doses of inactivated vaccine. It is planned to administer V-01 booster shots or placebo to 10,772 healthy adults aged 18 and above who have completed two doses of inactivated vaccine 3-6 months prior, in a 1:1 ratio. As of the key data analysis date, 10,241 individuals were actually enrolled, and a total of 110 primary endpoint cases were monitored after vaccination (the protocol requires analysis when at least 103 primary endpoint cases are observed). The results of the interim analysis showed that compared with two doses of inactivated vaccine, the incidence rate per person-year in the V-01 sequential booster group and the two-dose inactivated vaccine group was 6.73% and 12.80%, respectively, with a significant difference (P=0.0012); the absolute protective efficacy of V-01 after sequential boosting was 61.35%, demonstrating significant superiority and meeting WHO standards.

It should be particularly noted that, unlike traditional placebo-controlled trials, the V-01 sequential booster Phase III program uses a superior efficacy standard for relative protection. That is, the results compare individuals who have completed two doses of inactivated vaccine, and also consider the impact of natural immunity in the experimental population as the epidemic evolves. Compared with other placebo controls, the base number is higher, so the absolute protective efficacy of 61.35% is quite excellent.

In addition, V-01, as a booster shot, can rapidly and significantly increase neutralizing antibody titers, effectively combating multiple mutant strains. Genotyping sequencing of 60 of all valid samples submitted in this trial was Omicron (the rest are still undergoing next-generation sequencing), indicating that V-01 sequential boosting can provide good protection against COVID-19 caused by Omicron infection.

Regarding basic immunization, V-01 is undergoing Phase III clinical trials in countries such as the Philippines and Russia, and has currently reached the interim analysis target of the study design. Data cleaning and preparation for interim analysis are underway.

Better Safety and Superior Enhancement Effects in the Elderly Group

With the repeated global prevalence of mutant strains of the novel coronavirus, the risk of infection in the elderly is also increasing. Data from various countries have consistently shown that the risk of severe illness and death after infection with the novel coronavirus is significantly higher in the elderly than in adults and children, and the average age of death among COVID-19 patients reported by various countries is over 70 years old.

Preliminary analysis of clustered outbreaks in many parts of China this year shows that the risk of severe illness is significantly lower in vaccinated elderly people than in unvaccinated elderly people. However, data on cumulative reports of COVID-19 vaccination in China show that as of February 25, about 220 million people aged 60 and above have received vaccination, and about 211 million have completed the full course of vaccination. The vaccination rate remains low for those aged 60 and above, especially those aged 80 and above. Increasing the vaccination rate among the elderly is of great significance in reducing the mortality rate of COVID-19.

One of the significant advantages of recombinant protein-based COVID-19 vaccines is their higher safety, especially in elderly subjects. V-01, with its unique molecular design, exhibits better tolerability and immunogenicity in the elderly population.

In terms of safety, V-01 showed a lower adverse event rate in the elderly group than in adults. In the two-dose regimen group of its Phase II clinical trial (560 subjects in total), the incidence rates in the adult 10μg, 25μg test groups and the placebo group were 25.00%, 12.50%, and 15.00%, respectively; while in the elderly group, the incidence rates in the 10μg, 25μg test groups and the placebo group were only 10.00%, 12.50%, and 5.00%, respectively.

From the perspective of immunogenicity, V-01 also showed good protective effects in the elderly population. In Phase I and II clinical studies, adults and the elderly were enrolled at a 1:1 ratio (a total of 530 elderly people were enrolled). Data showed no significant difference in safety and neutralizing antibody titers between the adult group and the elderly group.

Its boosting effect in the elderly population is also no lower than that in the adult population. The results of the Phase I clinical trial of V-01 boosting immunization showed that after V-01 was used as a third homologous booster shot, the neutralizing antibody levels against live viruses (Delta and wild-type) increased rapidly and significantly. Compared with before the booster shot, the neutralizing antibody titer in the adult group increased by 60.4 times after boosting immunization, while the neutralizing antibody titer in the elderly subjects increased by 53.6 times, with comparable boosting effects between the two groups.

New variants of the coronavirus are emerging fiercely, especially during the Omicron pandemic, where the risk of severe illness and death from infection is very high in the elderly. V-01 may provide more options for basic immunization and booster immunization in the elderly.

Domestically sourced raw materials enable mass production and stable supply.

Affected by various factors such as vaccine storage and production, nearly half of the global population has not yet been vaccinated against COVID-19. In low-income countries, the COVID-19 vaccination rate is only 2%. In addition, with the continuous mutation of COVID-19 variants, there is still considerable uncertainty in epidemic prevention and control, and overseas epidemic prevention and control will still face a "protracted war". Although many countries have started booster vaccinations, under the background of the global prevalence of the Omicron variant, the decline in the protective efficacy of various COVID-19 vaccines, and the uneven global distribution of vaccines, there is still an urgent need for booster vaccinations abroad, and safe and effective vaccines still have broad market prospects.

In China, although the COVID-19 vaccination rate is high, it still faces the challenge of the continuous spread of global variant viruses. With the official launch of sequential booster immunization in China, there will be a large demand for booster shots. Zheshang Securities predicts that the potential market space for booster shots in China may reach 70-80 billion yuan.

Compared with other technical routes, recombinant protein COVID-19 vaccines are more conducive to widespread penetration in developing countries and regions lacking sufficient medical facilities due to their relatively simple mass production and low storage and delivery requirements. In addition to the advantages of 2-8℃ cold chain transportation and long-term storage, V-01, based on advanced molecular design, has pioneered the domestic production of raw materials, and can be sustainably and stably supplied in large quantities after listing.

In terms of molecular design, V-01 innovatively integrates human interferon as a biological adjuvant, which can be combined with common alum adjuvants to enhance immune response while avoiding severe toxic side effects. This strategy not only avoids the production and safety issues of new adjuvants, but also avoids the dependence on strong adjuvants with large side effects and patent monopolies for protein vaccines, which helps to continuously and stably release production capacity and reduce costs during widespread application.

In terms of production capacity preparation, it is understood that the bulk drug production line and preparation production line of Lizhu V-01 have passed the on-site inspection of the Guangdong Provincial Drug Supervision and Administration Bureau for vaccine production licenses, have the production conditions, and have obtained vaccine production licenses. The expected bulk drug production capacity can reach 3.5 billion doses, and the preparation production capacity in 2022 can reach 1.5 billion doses. The production capacity reserve scale is ahead of the recombinant protein vaccines that have been listed or have been granted emergency use authorization.

Source: Hongkan Finance