Distinguished guests, ladies and gentlemen, good afternoon. Welcome everyone to Brii Biosciences Virtual HBV R&D Day. I am today's host, Rico Liang, General Manager of Brii Biosciences Greater China. On behalf of Brii Biosciences, I would like to express my gratitude to all of you, and welcome any questions during the meeting. We will have a Q&A session by the end of the meeting. Firstly, please allow me to introduce the guests today. They are Professor Zhuang Hui, Academician of Chinese Academy of Engineering. Dr. Hong Zhi, Chairman and CEO of Brii Bio. Dr. Zhu Qing, China R&D Head of Brii Bio. Thank you so much for your participation. Chronic hepatitis B is one of the most serious infectious disease in the world, with more than 250 million infected people. In particular, China is facing with heavy burden of this disease.
Latest research result shows that HBV infection rate in China is 5.6%, covering 79 million people, and about 400,000 new infection-related liver cancer diagnosis every day. For a long time, Brii has always been adhering to the value of putting people first and the patient first, and is committed to provide the most advanced preventive and clinical curative therapy for hepatitis B. Eliminating hepatitis B is always our mission. Today, we take this opportunity to discuss with you the strategy in China to eliminate chronic hepatitis B. Firstly, I would like to invite Dr. Hong Zhi to deliver opening remarks, please.
Thank you so much, Rico, for your introduction. Dear experts, ladies and gentlemen, welcome to Brii Biosciences second hepatitis B R&D Day. We really want to use this opportunity to do some academic exchanges with all the colleagues in the industry. I will also take this opportunity to briefly introduce some of our thoughts on the layout pipeline strategy of Brii Bio in the field of hepatitis B treatment. Thank you so much for participation. Brii Biosciences was founded in 2018, five years ago. Our mission has always been to meet the challenges of public health with breakthrough scientific innovations and insights into the key needs of patients. Our focus areas have always been infectious diseases and central nervous system disease.
We hope to make the first and innovative treatment programs and methods in all of these areas. Challenges with the public health has the following characteristics. First, there is a large number of patients. Second, when patients suffer from serious diseases, they face great social discrimination. Third, the options for treatment are very limited. You must have a deep understanding of what happened in the past three years during COVID-19 pandemic. Also, during these three years, the entire staff of Brii Bio withstood the big challenges. At the beginning of 2020, we stepped forward to take the responsibility of China and the safety of the people. In two and a half years, with record-breaking speed, we developed successfully and marketed China's first new coronavirus neutralizing antibody, and this is unprecedented in China, as such a great example of scientific translation.
Of our staff, in response to the emergency of COVID-19, Brii Bio cooperated with government agencies and hospitals between June and December 2021 to donate nearly 3,000 doses of amubarvimab and romlusevimab combination for emergency use in 13 provinces, which is such an unprecedented record of [uncertain] use in China. Nearly 1,000 patients received the treatment, and we have made our contribution to China's successful fight and the victory against the Delta variant in China. For this reason, we are very proud. We also made some contribution to our partners like Tsinghua University, The Third People's Hospital of Shenzhen, as well as Beijing and the Shenzhen municipalities. At the end of last year and the beginning of this year, with the sudden change of pandemic situation, we decided to return to our main pipelines of infectious diseases and the central nervous system diseases.
You can see that we have made great expansion and progress in the hepatitis B product line and the neurological disease production line in recent years. Today, we hope to give you a further introduction to the layout and pipeline of our hepatitis B product lines. The elimination of hepatitis B is the hope and the request of the international society. As early as 2016, the WHO formulated a very clear goal of eliminating hepatitis B by 2030, which includes the goal of prevention, reducing the new hepatitis B infection by 90%. The goal of diagnosis rate is 90%, and the goal of treatment rate is also 90% for eligible patients, so that we can reduce the death rate by 65%. We know that these goals are ambitious without good preventive vaccine and effective curative treatment.
Today, we are very honored to invite Academician Zhuang Hui, who represents Chinese Foundation for Hepatitis Prevention and Control and the Chinese Society of Hepatology, Chinese Medical Association, to introduce to us how China cooperates with WHO to reach the goal of eliminating hepatitis B by 2030. After Professor Zhuang Hui, Dr. Zhu Qing will share with you a more systematic introduction of Brii's hepatitis B prevention and cure strategy and pipelines, including an optimized recombinant preventive vaccine, PreHevbrio. We've seen in humans that it enables the strongest and longest lasting surface antibody response and a broad T- cell response. Among the treatment and the cure project, we have three projects. BRII-179 is an optimized recombinant therapeutic vaccine. We have also carried out evidence collection in clinical scenarios. We have seen that the preventive vaccine can induce the strongest anti-HBs response and a broad T- cell response.
The safety profile is wow after administered in 180 patients. The second, BRII-877, is a comprehensive antibody with a broad spectrum surface antibody. We have also carried out a lot of evidence collection in the clinic application, which proves that it's very efficient at 6 mg, which can reduce the concentration of surface antigen in human body. It has a very good safety profile, has been administered to more than 240 patients. Last but not least, BRII-835, which is the HBV targeting small interference ribonucleic acid, siRNA, which can degrade the viral transcripts and reduce viral antigen levels. A lot of clinical evidence has been collected showing that it can effectively reduce the concentration of surface antigens.
In terms of safety profile, it has been administered to nearly 400 patients. The proof of safety is very good. Here, I would like to leave more time to Professor Zhuang Hui and Dr. Zhu Qing. I would like to express again my gratitude to all of the guests for your attention to Brii Biosciences. Thank you so much. I wish this meeting a complete success.
Thank you so much, Dr. Hong Zhi. As Dr. Hong Zhi said, our mission is always use the breakthrough in science and technology to respond to public health issues, and the WHO has set a clear goal for the elimination of HBV by 2030. Be prevention and treatment and cure, we have best solutions. Before we introduce our pipeline for R&D, I would like to invite distinguished Professor Zhuang Hui to introduce the strategies of China in the elimination of hepatitis B.
Thank you so much, General Manager Rico, and I would like to pull up my slides. Distinguished Dr. Rico, Dr. Hong Zhi, Dr. Zhu Qing, distinguished experts, colleagues, ladies and gentlemen, good afternoon. Firstly, I want to thank Brii Biosciences for inviting me to participate in this chronic hepatitis B R&D. I wish this meeting a complete success. Today, my topic is expand screening, expand prevention, expand treatment in order to eliminate hepatitis B. In 2016, at the WHA 69, WHO proposed the aspiration to eliminate hepatitis B, viral hepatitis, and the WHO also passed the re solution in this regard with the signature of 169 countries, including China.
By 2022, the 75th World Health Assembly, WHA, adopted a resolution on the global health sector action plan on HIV AIDS, viral hepatitis, and the sexually transmitted disease from 2022 to 2030, posing the goal to, and the strategies to eliminate viral hepatitis. It added goals for 2025. Since the proposal from 2016 and according to baseline situation in 2020, the goal is to reduce the infection by 90% and the death by 65%. These are the two primary goals in order to contain the viral hepatitis. That means by 2030, infection reduction by 90% and a death reduction by 65%. In May 2022, at the 76th World Health Assembly, it was proposed that the goal for 2025, that is by 2025, the infection from 1.5 million to 850,000.
The death reduced to 530,000. That means we will cut the infection rate by 90% and the death rate by 65%. In order to meet these two goals, WHO made five methods or five measures. The first one is hepatitis B vaccination for the neonate. The three dose hepatitis B vaccination rate should be 90%, and the first dose of hepatitis B should be over 90%. Secondly, the blood safety 100%. Thirdly, injection safety 100%. Fourthly, the reduction in harm. That means to provide for free the injector for the drug user, and this rate should be over 83%. The fifth goal is the diagnosis treatment of HBV, and the diagnosis and treatment of hepatitis C should improve accordingly, respectively to 90%, 80%, 90%, and 80%.
If we can reach the five goals, we can reduce the hepatitis B infection by 90% and the hepatitis death by 65%. How is the current situation? At global level, we can see we still don't have information for the free injector for the drug users, but we do have some other, for example, the three dose hepatitis B vaccination rate is 87.7%, and the first dose of hepatitis B vaccination rate is 47%. The big gaps lie in the diagnosis and treatment of hepatitis B. China is much lower than the average level across the world. For example, the first dose of hepatitis B vaccination and the three dose of hepatitis B vaccination are much higher than the goal proposed by WHO for 2030 .
For example, the first dose for neonates is 96%, and the three dose vaccines have a coverage of 99%, already surpass the 90% goal of WHO and the blood safety 100%. There is still gap in the diagnosis and treatment of hepatitis B. For diagnosis of B, 22.1%, and for the treatment of B, 15%. There is still a big gap from the goal proposed by WHO. In recent years, we have made decent progress. You can see, this is the epidemiology survey in 1992, and you can see this is the red line, and the pink curve is 2006. You can see it dropped to 7.18% for the general population.
The brown curve is 2014. It only surveyed the people under 30 years old, without information for people over 30 years old. You can see that the surface antigen prevalence shows a decline. The fourth curve, the green one, is for 2020. Already the data has been published, but the paper hasn't. According to epidemiological survey, the prevalence rate of the surface antigen has dropped to 5.86%. Regarding the population less than five years old, the drop is more significant, and it was, in 1992, 96.9%, but it dropped to Oh, sorry. It was 9.67%. It dropped to 0.3%, and the goal of WHO is to cut it to 0.01 at 0.1% by 2030. That means, kids under five years old, the prevalence of surface antigens should be lower than 0.1%, and we have reduced it by 96.9%. Zhejiang Province just published a result.
For example, the survey on 1992 and 2006 and 2014 and 2020, there is no surface antigen for the kids under five years old, nor under 14 years old. Surface antigen positive only happens over 30 years old, but it's still low, only 7.3%. You can see we already cut to zero the surface antigen positive prevalence for the age group under five and under 15. We have made very good progress in the control of the surface antigen positive. We can also see that we have very high the surface antigen for the Zhejiang Province. On the right-hand side, this is the anti-HBc prevalence rate. That means these people have been infected by hepatitis virus, or they are currently carrying the virus. You can see from 30 to 69 years, and it's 51.7%. Some people, they have been vaccinated.
At least in this age group, 30%-40% of the people are susceptible to hepatitis B virus. They need to be vaccinated. What measures should we take? Firstly, we need to expand the prevention. For example, the three-dose vaccination for neonates now is 99% in China. Secondly, we need to expand the coverage of first dose vaccination, now is 96%. Thirdly, blood safety and reduce harm. We should also improve our efforts in this regard. China is good at blood safety, 100%. Safe injection and reduce harm. We will also meet the goal set by WHO for 2030. Of course, we need to consider to expand the vaccination for the susceptible adults. In April 2020, U.S. proposed universal vaccination against the hepatitis B for the people aged 19 to 49. In the past, it proposed the vaccination plan for all the neonates in 1992.
In 1999, U.S. proposed to vaccinate all the people under 18 years old. At this time, U.S. proposed the theory that all people should be vaccinated between 19 to 59 years old. If the people are above 60 years old, they should also be vaccinated, or any people willing to take the jab can also get one. These are the three new measures. Vietnam also set the goal to eliminate HBV and to improve the immunization coverage of the people. Why should we vaccinate adults with the vaccines? You can see, people over 30 years old, they still have a high possibility to get hepatitis B, because if we improve the vaccination rate for neonates, the major group for hepatitis B infection is adults.
In China, we can see from 2005 to 2016, the incidence rate of hepatitis B for the people over 30 years old is very high. You can see these curves are for 30 years old, 50 years old, 40 years old, and 60 years old. They have very relatively high incidence rates of hepatitis B. At the same time, the protection rate and coverage of vaccines for the adult groups are low. You can see the age group from 25 to 49, and these are the people over 50 years old. You can see the coverage rate is low and the susceptibility is high. For the people from 25 to 49 years old, the susceptibility is 65%. If the people are over 50 years old, the susceptibility is 81.6%.
That is the result for U.S., and in China, for the people over 14 years old, the vaccination rate is low, like 48% for the people over 15, under 25, and much lower for elderly people. The Weihai Municipality also carried out an epidemiological survey, and we can see that the HBsAg positive rates are still high for all the age groups. These are some results of the epidemiological survey. From five to nine, from 10 to 14, because they have taken the vaccine, their susceptibility is low. But if a person is over 15 years old, the susceptibility is elevated almost to 30%. We estimate about 30%-40% of adults in China are susceptible, so they need to be vaccinated. This is reported by Zhejiang Province. They have two counties, Putuo District or Putuo County, and Dinghai District.
They draw a parallel between the two districts. So 20 to 59 years old, without three doses of vaccination, they can receive the vaccination for free. We can see the HBsAg positive high and the surface antigen positive is low. This is the intervene group. That means we need to give the vaccination to the people susceptible to hepatitis B. In this way, we can reduce the infection and reduce the onset. The vaccines against the hepatitis B for adults can have different schemes of administration, two doses or three doses. Both work. No matter which strategy or scheme, it can reduce the onset infection of all the viral hepatitis, like the hepatitis B or the chronic hepatitis infection, HCC, and HBV related death, and acute HBV infection. So, two dose or three dose strategies both work. Secondly, we need to expand the screening.
Detection, detecting earlier, diagnosis earlier, and the treatment earlier. In this March, CDC of U.S. proposed to enlarge the HBV infection screening and stating five measures. First one, screening for pregnant person. All pregnant women, each time of pregnancy, they need to receive one screening. That was proposed in 2018. For risk-based population, they also need to receive testing. This time they added a few more measures. First one is universal hepatitis B virus screening. Secondly, anyone who requests HBV testing can get one. Not only for the surface antigen, but also HBs and anti-HBc. Germany in this February also promulgated to expand the screening for HBV. China now is drafting the expert common consensus on the expansion of HBV infection screening. By the end of this year, we are supposed to have these new policies.
It also contains three items, HBsAg, anti-HBs, and anti-HBc. If we detect an infection, we need to give them treatment. If only surface or core, only HBs and anti-HBc are positive while their antigen is negative, maybe they have been infected, but now they have recovered. We need to evaluate their reactivation risk. If they are receiving the anti-tumor treatment or anti-immunological treatment, before the treatment, we need to give them preventive treatment for hepatitis B. The third possibility is anti-HBs is positive and the other two are negative. That means they have been vaccinated. Fourth, all three are negative. We suggest to give them hepatitis B vaccines. The fifth possibility is anti-HBc is positive. They could be false positive after infection, or we should do further analysis of the reason and then give them treatment accordingly.
This is the universal screening for the adult from 18 to 69 years. By doing this screening, we can reduce 30% for the decompensated hepatitis and compensated cirrhosis by 43%, and the HCC by 23%, and liver transplant by 24%, and HBV-related death by 27%. We suggest to do the universal screening for all the people between 18 to 69 years old. We also need to combine the treatment after the screening. According to different results of the screening, we can provide the people with different strategies of treatment. This is the paper published in Australia. After the screening, if we can provide timely diagnosis and treatment, according to the positive, negative of the three indicators, we can effectively cure the disease. Immediately after the screening, we need to provide with diagnosis and treatment.
China has a big coverage of screening before pregnancy, after the surgery, or a high-risk population or patients. Every year, China screened 760 million people. Our diagnosis and the treatment lag behind. That means after the screening, we only provide neonates with some prevention. If some surface antigen is positive, we will give them a treatment, immunoglobin, and if negative, we will give them vaccine without the immunoglobin, but we don't have any treatment for the pregnant women. If their surface antigen is positive and there is no treatment, and for the surgery, if the screening result is positive and treatment and the diagnosis lag behind. For the donation personnel, we screen every year 24.6 million. If result is positive, and we don't have follow-up data, what kind of diagnosis and treatment we provide to them.
If we don't do diagnosis and treatment, the screening doesn't make any sense. For China, the problem is that we need to bridge the gap between the screening and the diagnosis and treatment. This is so important for the people after the screening. The third aspect in my presentation is expanding treatment. In China, the diagnosis rate is 22%, the treatment rate is 15%. United States is not high, and the diagnosis rate is 90%. Among them, 29% receive treatment. So, diagnosis rate and the treatment rates are low. Now, United States, the Hepatitis B Foundation proposed to streamline the treatment, expand the treatment, and streamline the standard for treatment. If it's HBV positive, with or without the enzyme elevation, we need to provide treatment. In other situation, if the HBV is more than 2,000 units, we need to provide treatment.
Even we do this, the treatment rate is only 33%, far behind the 80%. If we cannot meet the goal of 90% of diagnosis rate and 80% of treatment rate, there's no mean for us to reduce the death rate by 65% and the infection rate by 90%. So, we must improve the diagnosis and treatment rates. China also published our new policies by the end of last year in November. For HBV positive, we need to provide treatment because there is a cirrhosis, and the infection, and the transplant, and death risks, and also transmission to other people, and the stigma, and the quality of life, and can reduce the rate of pregnancy transmission. So, HBV positive treatment. This year, the Serum Institute of India also published a paper titled, "Treat All or Treat Selected." If we do treat all, we can improve diagnosis and the treatment rate.
You can see this is treat all strategy, green curve. Diagnosis rate improved a lot and the treatment rate elevated a lot. The new infection reduced significantly for both the acute cases and the chronic cases. Death related to hepatitis or liver diseases reduced by 50%. So only by doing treat all can we meet the goal set by WHO. Infection cut by 90% and the death cut by 65%. In 2022, China published the new treatment guideline for HBV. According to the new treatment guideline in China, there are 81 million HB surface antigen negative infection in China, and our estimation is 45 million. But in this guideline, it estimates there are 81 million. Among them are 75 million infections more than 30 years old, that they need to receive treatment. So this rate is 92%.
The people under 30 years old, if it's cirrhosis, they need to receive treatment. If it's more than F2, phase II, and the ALT more than ULN, or history of cirrhosis or HCC, or extrahepatic manifestations. Well, if we add them together, it's more than 95% and almost treat all. If we can do that, over 95%, we will be not far away from cutting the death rate by 65%. So don't wait. Don't wait is the slogan set by WHO this year. We need to get people tested, vaccinated, and treated for hepatitis B. It could save the life. This is the hepatitis day, and one person has one liver. We must appreciate, and we must take care of our liver. In China, the slogan is that earlier prevention, earlier detection, earlier diagnosis, earlier treatment.
We can see we have different cultures, but they are on the same page. Earlier prevention, earlier diagnosis, and earlier treatment. This is only way to reduce the incidence rate by 90% and the death by 65%. New infection reduction by 90% and the death rate by 65%. Thank you so much.
Thank you so much, Professor Zhuang Hui, for his wonderful speech. He showed very clear the strategy of China to eliminate hepatitis B. We can see that from prevention to treatment, there is still a big unmet need, and there is still a big gap from the goals set by WHO. For example, the treatment rate in China is 15%. Regarding prevention, the coverage rate for the adult people vaccinated is very low, and the susceptibility is very high, about 30%. All of these are unmet needs. What should we do in order to realize the elimination of hepatitis B by 2030? Professor Zhuang also showed us the clear pathway. Earlier prevention, three doses for neonates. For the susceptible people over 18 years old, they must be vaccinated.
For the people exposed to high-risk work, they also must take vaccines and receive regular screening. Secondly, screening. Screening for all, especially for adults. At least they need to receive one screening to see whether they are susceptible or people need to be treated. The second one is treat all strategy. According to China's new treatment guideline, all the people who need treatment should be treated. Don't wait. Earlier prevention, earlier diagnosis, earlier screening, earlier treatment. This is the only way to eliminate chronic hepatitis B. Again, thank you so much, Professor Zhuang. Next, I will give the floor to Dr. Zhu Qing to introduce what pipeline strategy of R&D Brii Bio has.
Thank you, Dr. Rico. Firstly, I want to thank Professor Zhuang Hui for the wonderful sharing. Good afternoon. Thank you so much for taking time from your schedule to take part in this meeting. Every time I listen the presentation of Academician Zhuang Hui, I learned a lot. This time, I will introduce to you the strategy and pipeline of Brii Biosciences in the hepatitis B treatment. Before my introduction, I would like to briefly introduce our pipelines. In the past several years, if you are familiar with us, you must know that in the past three years, we are devoted to the treatment of functional treatment, functional cure. There are three products. Later you can see their progresses.
With the clinical progress, this year we introduced the preventive vaccine. Professor Zhuang said that the WHO set the goal for the elimination of hepatitis B. If we cannot tackle the problem of prevention treatment, there will be no way. We have very good coverage of vaccination for the neonates , but not so good on adults. There is a big amount need there. I will spend 20- minutes to firstly introduce the PreHevbrio for adult, and then I will introduce the functional cure solutions. Firstly, let's take a look at high-risk population and underprotected population. China and other APAC countries are very good in terms of giving vaccination to all the neonate s. But due to the following reasons for the high risk, underprotected adults are not fully protected by the hepatitis B vaccination. China is less than 30%.
For the susceptible population of 30%-40% of vaccination rate, very low. For traditional vaccines, when the neonate s gets grown up and the immunity will get less strong, then 10% of the patients of the people, they are not responding to the virus when they are grown up. There is individual difference from one to one, especially for the elderly people and susceptible people, HIV AIDS carrier or obesity or smokers. All of these susceptible people, they are not good responders to traditional vaccines. Brii Biosciences or PreHevbrio, this is our licensed new drug. You can see the licensed territories cover Greater China region, mainland China, Hong Kong, Taiwan province, and you can see also some other Asian countries.
Why we want to get all of these licenses, because these are the places with high prevalence of hepatitis B and with a large population of underprotected people. There are more than 150 million HBV-infected people in this region. The susceptible population is as high as 500 million. If we can use this very good preventive vaccine, we can effectively reduce this burden. This vaccine has been marketed in multiple countries, United States, Canada, European Union. Professor Zhuang said that CDC of China stresses that all adults are suggested to take hepatitis B vaccine, and this vaccine is recommended by CDC, in United States to their adults. Firstly, I would like to introduce what is the difference between PreHevbrio and other vaccines. You can see this structure.
This is the variant, and you can see the DNA is [uncertain] the nucleocapsid are at the center. At the surface, there are three different surface antigens. You can see the spikes are different, and this kind of spike without the yellow ball, and they are the green smaller ones. We call them the small surface antigens. Normally, other marketed vaccines only contain one, this one. The other, the Pre-S2 and the Pre-S1, they are medium-sized surface antigen envelope protein and the large envelope protein. They contain the hepatitis B virus hepatocyte receptor binding sites, and they can trigger very strong immunological responses. Our vaccine has all the three types of envelope proteins, and they are also expressed in the infected virus.
This after the expression of mammalian cells and the develop B or wild type into envelope, while the traditional marketed vaccines, they only contain the small envelope proteins. Due to different types of the envelope vaccines, there are different profile in terms of the immunogenicity. First one, because it expresses in mammal cells, so it has the correct glycosylation pattern. It can fold to its native conformation, resembles the naturally occurring HBV particles in terms of protein composition. We can see this is the pivotal phase III trial for registration. When we evaluate the immunogenicity on different groups including healthy population in the middle, you can see this is a comparison to the second-generation vaccine, ENGERIX-B, and you can see there is the line. More to the right-hand side, it has higher superiority.
This is over 65 years old or between 45 to 69 years old, who has compromised immunity and are not good responder to traditional vaccines. After taking the PreHevbrio vaccines, the result is much better, like 10%, 15% of the population can have serum protection. The titer, you can see at least five times larger is the titer after the protection of PreHevbrio, and the titer is much higher, five times. We also evaluated for the susceptible population, for example, with diabetes, with obesity. We can see the advantage is even more obvious. We also evaluated among the population after three years of vaccination, the serum concentration titration, and what is the difference between our vaccine and other marketed vaccines. You can see after the immunization, the difference is big, just big.
Three years after, the titration difference is still five times, and the blue curve is traditional vaccines. It dropped to less than 200 units, while PreHevbrio is more than 1,000 units. This is so significant a difference. There are three highlights. If you remember something, just remember these three highlights. The first one, the rate of serum protection is high and very quick. After two doses, the titration will increase rapidly, and the immunogenicity very strong and very long-lasting. We introduced the adult preventive vaccine. This slide you can show some of our strategies of marketing. First of all, of course, fast access to APAC region. Not only we got EU, U.S. licenses and we'll also submit application in Hong Kong. We expect to get the approval by the end of this year. In other countries in Asia, we are also communicating closely with regulators.
We will give priority to the countries which do not require additional trials to do the registration, and we'll find commercialization partners. We are also communicating with CDE of China to make it clear our strategy for registration in China. Of course, we want to bring this very good vaccine to China as soon as possible, especially for the adults and for the adults with higher risks. After talking about this preventive vaccine, I will spend more time for the functional cure. What we have done in these years. As you can see here, I don't need to repeat this part because you know it very well. It's very complex disease. Most of the infected people, they got infected when they are very young, for example, from their mother or some vertical infection. Therefore, when they have onset, they had already carried the virus for many years.
There's a very clear trait in the difference of their immunological harms. Sooner diagnosis, sooner treatment definitely will make a difference. The standard treatment is to use the nucleocapsid, so that we can reduce the burden of the virus. We can use the natural immunological interferon, and these drugs have been used in the market for 20 years. It works so good, especially in the suppression of the DNA. But it has a big limitation, which is after using the interferons, they need to take the drug permanently. For the hepatitis B patients, we hope that we can develop some solution.
For example, after a certain period of treatment, patients can discontinue administration, just relying on their own immune system to control the infection of the virus, and also go back to normal life without any concern of the hepatitis B or any possibility to get cirrhosis or HCC. The new combination therapy may lead to higher functional cure, and the one combination with consensus is to reduce the antigen and to recover the immunity of the host. In order to have functional cure, we must have a combination of different treatment and of different mechanism of action so that we can reach the goal that there is no surface antigen or DNA detected after discontinuation, and no relapse, no spontaneous relapse. With time, goals to reduce the cccDNA or eliminate cccDNA over time through sustained immunological control and for a complete cure.
On the left-hand side, we can see the life cycle of a virus, from virion entry, amplification, and the packaging and secretion of the antigen. It doesn't contain all of these whole viral genes or these cells. Because this kind of surface antigens, they lower the immunity or deplete the immunity. Therefore, to improve the immunity, for example, innate immune responses and adaptive immune responses, they are so important. Therefore, the first candidates in the combination, they must have the features to induce the strong anti-HBs responses and broad T-cell responses against the Pre-S1, Pre-S2, and S. Professor Hong mentioned that we have three projects. The last one is BRII-835, and it will target all the siRNA.
In the last two to three years, we worked together with our partners in doing phase I and phase II trials in chronic hepatitis B, where you can effectively degrade the viral transcripts and reduce the viral antigen levels. We have administered the combination to 397 patients. We have very good safety profile. The second solution is BRII-877, and it's the most potent surface antibody in reducing surface antigen and preventing reinfection. We have made some modification on the surface, and not only increased their neutralization ability, but also to improve their combination to the immunological cells. We can effectively reduce the HBsAg. The last one is BRII-179, and I think this is optimized the recombinant vaccine, and for the chronic hepatitis B. On this slide, I can do a summary.
In the past two years, we did the single therapy trial of the three vaccines each, three treatment each. Since this year, we have started to do some combination trial to see which is the best combination. Here, what you can see is that the studies and trials we are doing, including the combination of BRII-179 and BRII-835, and BRII-835 and pegylated interferon- alfa, and also together with our partner. Sorry, our partner is doing the BRII-835, BRII-877, with or without pegylated interferon- alfa, and we are also doing BRII-179 with pegylated interferon- alfa. Later we can elaborate more on the scientific strategy. We have a small sample. This trial carried out by our partner, which is the combination of BRII-835 and pegylated interferon- alfa, and our combination, their combination has a slight difference.
You can see that two off-treatment data was presented at EASL in June 2023, also at the APASL in February this year. Now I can share with you some highlights of our data, also some newly launched trials and researches. The first one is combination of BRII-835 and pegylated interferon alfa. The design has been showed to you before. The design is asking some questions. All the siRNA are the control group. We want to see whether we can improve the functional cure possibility. Pegylated interferon at different time windows, or we give the two treatment at the same time, six months or 12 months, or at the same time, the siRNA and the pegylated interferon at the same time.
At the early phase, after the treatment, the result was very encouraging because the siRNA and the pegylated interferon take a long time, up to 48 weeks. The surface negative conversion rate is very encouraging, up to 30%. I want to stress is that the trial was not limited to baseline surface antigen. We know that interferon works well is when it less than 1,500 IU/mL, but the baseline, lower is the baseline, better is the result. This study is open to all the patients. You can see the negative conversion rate contains some patient with very high baseline. Just because of this, we are looking forward to see the follow-up results of these patients. You can see the follow-up result. We clearly see some rebounds, but many of them sustained the treatment effect, the negative status. This was released in United States this year.
As you can see that on the right-hand side, the people with rebounds, the Y-axis, this is anti-HBs at the end of the treatment. We can see is that the lower is the titer, higher is the possibility that the patient will have a rebound. At least more than 100 IU/L, or some of the patients more than 500 IU/L anti-HBs at the end of the treatment, they have sustained effect after the treatment. That means the level of anti-HBs at the end of the treatment can be an indicator to predict whether the patient will have rebound or sustained result. Interestingly, all the negative conversion patient has antibody responses. It's different from only receiving pegylated interferon and converting to negative. Because the sample is small, we don't have comparison of interferon. Later, we can see that we did something more in follow-up study.
Regarding the surface antigen, according to the requirement of clinical trial, we made some adjustment. They are very similar in previous studies. Later, after treatment of interferon and in the clearance, patient with clearance of surface anti, and if the titer is more than 100 IU/L at the end of the CHB patient achieving HBsAg loss by pegylated interferon-based therapy was associated with high rates of sustained HBsAg loss during follow-up. You can see this curve is less than 100%, and the lower curve is the surface antigen, less than 100 IU/mL. The higher curve is higher than 100 IU/mL. The increasing number of studies suggested that the presence of HBsAB secreting specific B cells in peripheral blood of CHB patients may be an important immunological indicator to predict the interferon treatment efficacy.
As the chart show, this is the proportion of serum conversion in CHB patients receiving interferon treatment comparing the ellipse part group, positive group and the negative group. For the antibody response and in our two studies, to study the BRII-179, we detected some interesting phenomena. The first thing is that the Brii, you can see this structure S antigen and the Pre-S2, Pre-S1. The structure is very similar to the preventive vaccine. It contains the small antigen Pre-S2 and the Pre-S1 antigens. What is the difference? For the purpose of treatment, firstly, the concentration is higher. Secondly, it has been optimized in terms of the adjuvant. It is a three-antigen therapeutic HBV vaccine formulated in adjuvant biased for Th1 immune responses. We use two clinical trials to evaluate this. One is a four-week, one dose to evaluate the B cell and the T cell.
We can see the specific T- cell compared to the doses is elevated. We also observe that some chronic hepatitis B patients, after receiving the treatment, there is some response of antibody. The proportion is changed. You can see the blue columns. In another study combining BRII-835 and BRII-179, because patient need to take the vaccination for nine doses, the effect is even more obvious. In this chart we draw comparison for the only receiving siRNA, and we can see different titers represent different titers. More than 1,000 units, very high. Around 20% of the patients belong to the blue part. The majority of the patients, that means more than 40% of the patient, after the treatment, they can have more than 100 IU/L . We also found that some patients don't have antibody response after the vaccination.
According to the result of these two clinical trials and the pegylated interferon, especially for the sustained serum conversion after the treatment of interferon, we have a hypothesis that patient who elicit good antibody response to BRII-179 with higher anti-HBs titers may have less dysfunctional immunological profile and may be able to achieve a better response to curative therapies. We can anticipate that people have different innate immunological responses. Some people after one dose, they have good response. Others even have taken many doses, they don't have a good response. We want to tell the patient with good baseline immunity from those who don't. In this way, the anti-HBs responders receive BRII-835, and the pegylated interferon- alfa therapy can have improved functional cure.
Brii plans for multiple combination studies with the earliest to start in second half this year, investigating the potential value of BRII-179 in combination regimen for increased functional cure. We will evaluate the hypothesis we just mentioned. Before the end of my presentation, I would like to make some introduction of BRII-877. If you pay attention to our company, you may find that we already got the IND approval from CDE. We will start the bridging trial of BRII-877. Firstly, you can see here, this is effective neutralizing antibody for people with different status. This is the patient after the treatment and they rely a lot on the doses. For this patient, the safety is very good. When it's less than 1,000 at the baseline, only 6 milligram can reduce one or two log.
Now there are more and more preliminary data which are supporting further evaluation of the potential of BRII-877 for functional cure in patient with chronic HBV infection. With this work together with siRNA, if we use them together, we can have more options for patients of different status, not only limited to the surface antibody selected patient, but also for a wider population. In China, we are making big efforts to do the bridging study. This is our partner, Vir, which is doing a phase II study. It is also called the MARCH study. It has two parts, part A and part B. In the European Liver Conference, it is reported that at the end of the treatment, their results of treatment and the results at the 48 weeks post EOT.
Firstly, we observe the PK and the PD to see whether it can be reduced. We can see different regimes, 75 mg or 18 mg. This is the fixed dose and siRNA in parallel or not in parallel, consecutive. Cohort three, at the end of the treatment, it reduced about three logs and 90% of the participant achieved surface antigen less than 10 IU/m L at the end of the treatment. Because this is a short duration of treatment and all the HBsAg levels rebounded in all treatment groups, but remained almost one log below baseline. The safety profile is very good. Now regimes evaluating 24 or 48 weeks with the BRII-877 with or without pegylated interferon- alfa are going. By the end of this year, we will publish the data.
Before the end of my presentation, I will briefly stress our Brii HBV cure strategy. siRNA plus pegylated interferon. According to different design and the protocol, we can foresee a good outcome of treatment. Based on that, and the interferon, our partner is completing the physical study. Meanwhile, you can see there is a group of interferon alone, and I also mentioned that siRNA and the 179 patients because they have good immunological profile. After the treatment, these patients are called back to receive siRNA interference so that we can evaluate the role of BRII-179, whether it can improve the rate of cure. We are planning and in discussion another clearer phase II study design. BRII-179 immunotyping plus BRII-835 or pegylated interferon- alfa.
In the next six months, you see some new clinical trial to be launched, so we can better evaluate the different combinations, which can better improve the target cure rate. Some expected date, we will publish the clinical trial results. In China, we will have a phase II study to evaluate BRII-179 on the patient who had been receiving pegylated interferon- alfa. The result will be published by the end of this year. By the end of this year, we will also share with you more outcomes, BRII-835 and the BRII-179 combination. Some other studies are about to be launched, and others are in process of design. My last slide. We have introduced the progress of our pipelines. The strategy is that we will be driven by data and to achieve functional cure.
We want to stress that our China team in the past years has made successfully early POC studies in APAC and mainland China. We have very good insights. We also have design execution for mainland China and the APAC region. Regarding the combination, regarding the life cycle of viral and other channels, we are also doing a lot of work of translation and clinical evaluation. Based on the data and our deep understanding of the unmet need, we will design our different strategies of combination. Based on that, we hope we can expand our pipeline and find the most optimal combination strategy so that we can bring this product to the market and to develop our combination as soon as possible so that we can help all the chronic hepatitis B patients. That's all for my presentation. Thank you.
Thank you for your long-term support and attention. Thank you for giving me this opportunity to share with you. Thank you. Thank you so much, Dr. Zhu, for your very detailed introduction, from prevention to functional cure. Just as Dr. Zhu shared, each candidate drug for hepatitis B developed by Brii, not only have unique mechanism of action but are best-in-class candidates. This gives us opportunity to provide potentially the best treatment option for different types of hepatitis B patient. Each program is designed based on the unmet needs of the patients. We have 10- minutes for the QA session. I can see that we are receiving many questions. Due to time constraints, we will take some frequent ones for Professor Zhuang and Dr. Zhu. You can also ask a question after the meeting.
Professor Zhuang, I have a question for you. Do you think China can reach the goal of eliminating hepatitis B by 2030? What should we do to achieve that?
There are five measures. Our biggest problem is diagnosis rate is only 22%, treatment rate is only 15%. If we want to eliminate hepatitis B, we must improve the diagnosis to 90% and the treatment to 80%. This is only way to reach the goal of incidence cutting by 90% and the death rate cut by 65%. We must work together to improve the diagnosis rate to 90% and the treatment rate to 80%. This is the only way for us to eliminate viral hepatitis by 2030. If we cannot do it, there would be no way, because we are good at the other three. I think this is only gap, but if we can expand the diagnosis and treatment rates, we can do that.
The big gap lies here. If we cannot make these two goals, meeting 90% and 80%, we cannot meet the goal. If we can improve diagnosis to 90% and treatment to 80%, we definitely can reach the goal of eliminating hepatitis B by 2030, namely reducing the incidence by 90% and the death rate by 80%.
Dr. Zhu, I have one question for you. Just elaborate more on this. Compared to other marketed vaccines, what strengths or advantages does PreHevbrio have?
There are some newly launched two-dose vaccines, so compared to that, what advantages do we have? We haven't got the data.
Sorry, the question is for Dr. Zhu. Dr. Zhu, can you answer the question?
Yes. We have pivotal trial data. This is the head-to-head to compare the second generation, the small surface envelope protein of ENGERIX-B. Because there are different components on the surface and the manufacturing mechanism, the immunogenicity is much higher. Therefore, in the head-to-head trial, we can see that the immunogenicity is stronger and longer lasting, and the titer is significantly higher, especially for the susceptible adults. There is a newly launched two-dose adult vaccine. If we only compare two dose, the serum protection rate is similar, but I must say you have head-to-head the comparison. The titer of anti, I think the PreHevbrio has the advantage. We therefore anticipate a longer lasting of protection.
Another question for Professor Zhuang. The question is that in your presentation you said earlier prevention, earlier screening, and earlier treatment and treat all is important. Some of the audience want to know which are the challenges in China in hepatitis B prevention.
First, the neonates without vaccination in 2019 to 2021 were vaccinated for the neonates without vaccination when they were born, and they were vaccinated during these three years. But the program was suspended after 2021. I think we should establish a routine program to give vaccination to all the neonates who had not been vaccinated when they were born. This is first thing. Second thing, for adults, the incidence rate of hepatitis B is high, and the adult group is the major group with incidence because they have lower immunity to the virus. The patients, 30%, 40%, they are not immune to hepatitis B. All the adults, especially the susceptible adults, should receive the preventive vaccine against the hepatitis B. Again, especially for the high-risk groups, susceptible people, they must receive the whole process, hepatitis B vaccination.
Third, any people willing to take hepatitis B vaccination should have one. Because there are still some social stigma to these patients. Anybody who are willing to receive the hepatitis B vaccination should be vaccinated. I think China is quite good in the first dose. Vaccination is more than 90% for the neonates. It cannot be 100% due to varied reasons. Some neonates will miss the first dose. It is difficult to get this score higher. The three-dose vaccination is already 99%. No headroom for improvement. For neonates, we are quite good. I think the headroom lies in the adult population. We will continue our vaccination scheme for neonates. The key is that any kid misses their first vaccination should have the second chance.
Especially, we should redouble our efforts in vaccinating the susceptible adults and any people who are willing to be vaccinated. This is the way to expand the prevention and eliminate the hepatitis B. Expanding prevention is one solution. Expanding screening, expanding prevention, expanding diagnosis, expanding treatment. Combining all the things together, can we reach the goal set by WHO, elimination of viral hepatitis? Thank you.
Thank you, Professor Zhuang, for this video answer. Due to time constraints, that is all for the Q&A session. From the introduction of Professor and Dr. Zhu , we know that elimination of hepatitis B is always the mission of Brii Biosciences. Let us join government agencies to scientific research institutes, to pharmaceutical companies, and we can make this dream a reality. It is not only solve the physical pain for patient, but also to help them get rid of the social stigma, and they get back to their normal life. Again, thank you so much for your time and participation, and the recordings. You can follow us in our social media website, and the recording of today's event is available at Brii Biosciences.