Brii Biosciences Limited (2137) Earnings Call Transcript & Summary

[Foreign Language] 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 guest of today. They are Professor Zhuang Hui of Chinese Academy of Engineering; Dr. Hong Zhi, Chairman and CEO of Brii Bio; Dr. Yongqing , 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 affected people. In particular, China is facing with heavy burden of this disease. Latest administrative research results shows that HBV infection rate in China is 5.6%, covering 79 million people and about 400,000 new infection are related to liver cancer [indiscernible] every day. For a long time, Brii has always been adhering to the value of putting people first and patient first, and this committed to provide the most advanced preventive and clinical curative therapy for hepatitis B. And end this hepatitis B is always our mission. Today, we take this opportunity to discuss with you the strategy in China to eliminate the chronic hepatitis B and 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, 5 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 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 [indiscernible] for treatment are very limited. You must have a deep understanding of what happened in the past 3 years during COVID-19 pandemic. Also during these 3 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 2.5 years with record-breaking speed we developed successfully and marketed China's first new coronavirus neutralizing antibody. And this is unprecedented in China. -- such a great example of scientific translation. our first half in response to the emergency of COVID-19 Brii Bio cooperated with government agencies in hospitals between June and December 2021 to donate nearly 3,000 doses of Amubarvimab and romlusevimab combination for emergency use in early provinces, which is such an unprecedented record of its static drug use in China, nearly 1,000 patients received the treatment, and we have made our contribution to China's successful fight and 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, Shenzhen Third Hospital as well as Beijing and 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 in the central nervous system diseases. You can see that we have made great expansion and the progress in the hepatitis B product line and the neurological disease production line in recent years. So today, we hope to give you a further introduction to the layout and pipeline of our hepatitis B product lines. So 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%. And the goal of diagnosis rate is 90% and the goal of treatment rate is also 90% for eligible patients and 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 China hepatitis prevention and control foundation and the liver disease branch of Chinese medical association to introduce to us how China cooperate with WHO to reach the goal of eliminating hepatitis B by 2030. And after Professor Zhuang Hui, Dr. Yongqing will share with you a more systematic introduction of Brii's hepatitis B prevention and cure strategy and pipeline, including an optimized recombinant preventive vaccine PreHevbri. We've seen in humans that it enables the strongest and longest lasting surface antibody response and the broad T-cell response. Among the treatment and the cure project that we have 3 projects, the BRII-179 is optimized recombinant therapeutic vaccine. We have also carried out evidence collection in clinical scenarios. We have seen that the preventive vaccine can induce strongest anti-HBs response and the broad T-cell response. The safety profile is [indiscernible] after administered in 180 patients. The second [indiscernible] is a comprehensive Anti body with a broad spectrum surface antigens . We have also carried a lot of evidence collection in the clinic application, which proves that this very efficient [ subcu ] [ 6 milligram ] 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 HBV targeting small interference renal nucleic acid, siRNA, which can degrade the viral transcripts and reduced 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. So here, I would like to leave more time to Professor Zhuang Hui and Dr. Zhu Qing. So I would like to [indiscernible] again my gratitude to all of the guest 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. So the prevention and treatment and cure, we have best solutions. So before we introduced 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 many 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 Day. 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 WHA69 WHO propose the aspiration to eliminate hepatitis B, viral hepatitis. And WHO also passed the resolution in this regard with the signature of 169 countries, including China. And by 2022, the 35th World Health Assembly WA adopted a resolution on the global health sector action plan on HIV/AIDS, viral hepatitis and sexually transmitted disease from 2022 to 2023, posting the goal to -- and the strategies to eliminate viral hepatitis and it added goals for 2025. Since the proposal from 2016 and according baseline situation in 2020, and the goal is to reduce the infection by 90% and the death by 65%. These are the 2 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 75th World Health Assembly it was proposed that the goal for 2025. That is by 2025 the infection from 1.5 million to 850,000, and death reduced from -- reduced to 530,000 . So that means we will cut the infection rate by 90% and a death rate by 65%. In order to meet these 2 goals WHO made 5 methods or 5 measures. The first one is hepatitis B vaccination for the neonate, the 3-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 diagnosis and treatment of hepatitis C should improve accordingly, respectively, to 90%, 80% -- 90% and 80%. If we can reach the 5 goals, we can reduce the hepatitis B infection by 90% and hepatitis death by 65%. So 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 3 dose hepatitis B vaccination rate is 87.7% and the first dose of hepatitis B vaccination rate is 47%. So the big gaps lie in the diagnosis and treatment of the hepatitis B. The China is much than the average level across the world. For example, the first dose of hepatitis B vaccination and [indiscernible] dose of hepatitis B vaccination are much higher than the goal proposed by WHO for 2030. For example first dose for neonates is 96%. And -- in the [ 3-dose ] vaccines have a coverage of 99%, already surpass the 90% goal of WHO and the [indiscernible] 100% but there's still a gap in the diagnosis and treatment of hepatitis B. For diagnosis of B 22.1% and for the treatment of B 15%. There is a little bit gap from the goal proposed by WHO. In recent years, we have made decent progress. You can see this is epidemiology survey in 1992, and you can see, this is the right line and that the pink curve is 2006. And 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. But you can see that is a surface antigen prevalence show a decline. And the fourth curve, the green one is for 2020. And [ correct ] data has been published, but the art the paper hasn't. So according to epidemiological survey, the prevalence rate of the surface antigen has dropped to 5.86%. Regarding the population, less than 5 years so the drop is more significant. And it was in 1992, 96.9% but it dropped to -- sorry, it was 9.67%, it dropped to 0.3%, and the goal of WHO is to cut it to 0.01% -- 0.1% by 2030. That means kids under 5 years old the prevalence of surface antigen should be lower than 0.1%. And we have reduced it by 96.9%. And Zhejiang provinces just published a result -- for example, the survey on 1992, in 2006 in 2014 and 2020, and that there is no surface antigen for the case under 5 years old nor under 14 years old. So surface antigen positive only happens over 30 years old. The base is still low, only 7.3%. So you can see we already cut to 0 the surface antigen positive prevalence for the group under 5 and under 15. So we have made very good progress in the control of the surface antigen positive. And we can also see that we have very high surface antigen for the Zhejiang province -- so on the right-hand side, this is the HBV prevalence rate, so that means these people has been affected by hepatitis virus or they are currently carrying the virus. You can see from 30 to 69 years and is 51.7%. And some people, they have been vaccinated. So at least in this age group, 30% to 40% of the people are susceptible to hepatitis B virus. They need to be vaccinated. And what measures should we take? Firstly, we need to expand the prevention. For example, the 3 dose vaccination for neonates now is 99% in China. Secondly, we need to expand the coverage of first-dose vaccination. Now is 96%. Thirdly, [indiscernible] and reduce harm. So we should also improve our efforts in this regard. And the China's good at [indiscernible] 100%. Fifth injection and reduced harm, we will also meet the goal set by WHO for 2030. Of course, we need to consider to expand the vaccinaiton for the susceptible adults. In April 2020, United States 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, United States proposed to vaccinate all the people under 18 years old. In this time, United States, proposed a [indiscernible] on all people should be vaccinated between 19 to 59 years old and if the people is above 60 years old, [indiscernible] should also be vaccinated or any people wanting to take the job can also get one. So these are the 3 new measures. Vietnam also started the goal to eliminate HBV and to improve the immunization coverage of the people. So why we should 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 lower the -- we improved the vaccination rate for the neonates, so the major group for hepatitis B infection is 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-year-old, 50 years old, 40 years old and 60 years old. They have very relatively high incident risk of hepatitis Bs. 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%. In China, the -- but that is the result for United States. And in China, the people over 14 years old, the vaccination rate is low, like for the 8 years old, for the people over 15, under 25 and much lower for elderly people. And the Wuhan Municipality also carry out epidemiological survey, and we can see that the HBS positive rates are still high for all the age groups. So these are some results of the epidemiological survey. From 5 to 9, from 10 to 14 because they have taken the vaccine so their susceptibility is low. But if a person is over 15 years old, the susceptibility is elevated almost to 30%. So we estimate about 30% to 40% of adults in China are susceptible, so they need to be vaccinated. This is reported by Zhejiang province. They have 2 counties Pujiang district or Pujiang County. And Dinghai district, they draw parallel between the 2 districts. So 20 to 59 years old without 3 doses of vaccination, they can receive the vaccination for free. We can see the HBS positive high and the surface antigen positive is low. So this is the interference group -- intervening 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. And the vaccines against hepatitis B for patients, for adults can have different theme of administration, 2 doses or 3 doses both work, no matter which strategy or scheme, it can reduce the outsize infection of all the viral hepatitis like the hepatitis B or the chronic had infection, HCC and HPV-related death and acute HBV infection. So 2 dose or 3 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 the United States proposed to enlarge the HBV infection screening and stating 5 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. And for risk-based population, they also need to receive testing. And this time, they added 3 more measures. First one is universal hepatitis B virus screening. Secondly, anyone who requests HBV testing can get one. And not only for the surface antigen but also HBS and HBsAg. Germany in this February also promulgated to expand the screening for HBV. And China now is drafting the expert common consensus on the expansion of HBV infection screening. So by the end of this year, we are supposed to have this new policies. So also contains 3 items: HBsAg, anti-HBS and anti-HBC. So if we detect an infection, we need to give them treatment. So if only surface accure -- on the HBS and 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 their treatment, we need to give them preventive treatment for hepatitis B. The third possibility is anti-HBS is positive, and the other 2 are negative. That means they have been vaccinated. Fourth, all 3 are negative. We suggested to give them hepatitis B vaccines. The fifth possibility is 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. And by doing this screening, we can reduce the 30% for the decompensated hepatitis and compensated cirrhosis by 43% and HCC by 23% and liver transplant by 24% and HPV-related death by 27%. We suggest to do the universal screening for all the people between 18 to 69 years old. And we also need to combine the treatment after the screening, so according to different results of the screening, we can provide the people with different strategies of treatment. And this is the paper published in Australia. After the screening, if we can provide timely treatment -- diagnosis and treatment. According to the positive negative of the 3 indicators, we can effectively cure the disease. So 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 high risk of population or patients -- and every year China screened 760 million people, but our diagnosis and the treatment lag behind. That means after the screening we only provided neonates with some prevention. If some surface antigen is positive, we will give them a treatment immunoglobulin if negative, we give the vaccine without immunoglobulin, 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 diagnosis lag behind it. And for the donation personnel, we screen every year 24.6 million. If results is positive, we don't have follow-up data. How do we -- what kind of diagnosis and treatment we provide to them -- and -- so if we don't do diagnosis and treatment, the screening doesn't make any sense. So for China, the problem is that we need to reach the gap between the screening and the diagnosis and treatment and 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%. And the United States is not high and the diagnosis rate is 90%, among them 29% receive treatment. So diagnosis rates 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 is HBV positive with results, 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 with this, the treatment rate is only 33% far behind 80%. If we cannot meet the goal of 90% of diagnosis rate and 80% of treatment rates, there is no mean for us to reduce the death rate by 65% and infection rate by 90%. So we must improve the diagnosis and treatment rates. And 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 stigma and quality of life and can reduce the rate of pregnancy transmission. So HBV positive treatment. This year, the [indiscernible] of india also published a paper titled treat all or treat for that If we do treat all we can improve diagnosis and treatment rate. You can see this treat all strategy, green curve. Diagnosis rates improved a lot and the treatment rates elevated a lot and the new infection reduced significantly for both the acute cases and the chronic cases. that's 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 a new treatment guideline for HBV. And according to the new treatment guideline in China -- in China, there are 81 million HBV surface antigen negative inflection 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 is cirrhosis, you need to receive treatment. If is more than up 52% and ALT more than [indiscernible] history of cirrhosis or HCC or extrahepatic manifestations. Well, if we add them together, it's more than 95% and almost to 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 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 B Day, and one person has one liver. We must appreciate that we must take care of our liver. And 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 the only way to reduce the incidence rate by 90% and death by 65%. New infection reduction by 90%, and death rate by 65%. Thank you so much.

Thank you so much, Professor Zhuang Hui for his wonderful speech. For he showed a very clear strategy of China to eliminate hepatitis B. So we can see that from prevention to treatment, there is still a big unmet need and that's still big gap from the goal that by WHO. For example, the treatment rate in China is 15%. And 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, 3 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 to take vaccines and receive regular screening. Secondly, screening, screening for all, especially for adults, at least you need to receive one screening to see whether they are susceptible or 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. So 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. [indiscernible] 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. And every time I listen to the presentation of academician Zhuang Hui I learn 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 3 years, we are devoted to the treatment of functional treatment -- functional cure. There are 3 products. Later you can see their progresses. With the clinical progress this year, we introduced the preventive vaccine and Professor addressed that the WHO stated goal for the elimination of hepatitis B. If we cannot tackle the problem of prevention treatment, there will be no way. And we have very good coverage of vaccination for the neonates but not so good adults. There is a big unmet need there. I'll also spend [indiscernible] to firstly introduce the PreHevbri for adult and then I will introduce the functional cure solutions. Firstly, I'll take a look at high-risk population and underprotected population. China and other Asia Pacific countries are very good in terms of giving vaccination to all the neonates. But due to the following reasons for the high risk under protected adults are not fully protected by the hepatitis B vaccination. China is less than 30%. For the susceptible population 30% to 40% of vaccination rate, very low. For the nontraditional vaccines, when new [indiscernible], grown up and the immunity [indiscernible] less strong than 10% of the patients. So the people, they are not responding to the virus when they've grown up. So there is the 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 PreHevbri, this is our licensed new drug. You can see the license territories to cover greater China region. China, Hong Kong, 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 lot of population of underprotected people. And there are more than 150 million HBV affected people in this region. And 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 and the professor [indiscernible] said that [indiscernible] of China, stresses that all adults are suggested to take hepatitis B vaccine. And this vaccine is suggested -- recommended by CDC in the United States to their adults. And firstly, I would like to introduce what is the difference between PreHevbri and other vaccines. You can see this structure. And this is the virion and you can see [indiscernible] is the [indiscernible] the new clear cost feed are at the center. At the surface, there are 3 different surface antigens. You can see the spikes our trends. This kind of spike without the yellow bar and they are the green smaller ones. We call them the small surface antigens. So normally, other marketed vaccines only contain 1, this one and the other, the Pre-S2 and Pre-S1, they are medium-sized surface antigen envelop protein and the large envelope protein. And they contain the Haptitis B virus hepatocyte biting sites and they can trigger a very strong immunological responses. So our vaccine has all the 3 types of envelope virus and they are also expressed in the infected virus. So this -- after the expression of [indiscernible] cells and the development [indiscernible] wild type interest [indiscernible] of 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 memo cells. So it has the correct like constellation pattern, it can fold to it's native confirmation resamples the naturally occurring [indiscernible] particles in terms of protein composition. We can see this is the pivotal Phase III trial for registration. And 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, and [indiscernible], and you can see there is the line more to the right-hand side, it is more -- has higher superiority. So this is over 65 years old or between 45 to 69 years old, who has compromised immunity and not good responder to traditional vaccines after taking the PreHevbri vaccines, the result is much better like 10% or 15% of the population can have serum protection. And the titer you can see at least 5x larger is the titer. After the protection of PreHevbri and the titer is much higher 5x. And 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 3 years of vaccination, the serum concentration titration and what is different between our vaccine and other marketed vaccines. You can see after the immunization the difference is big. Just a big. Two years after the titration difference is still 5 times and the blue curve is traditional vaccines. It dropped to less than 200 units while PreHevbri is more than 1,000 units. So this is so significant difference. Our 3 highlights, if -- remember something, just remember these 3 highlights. The first one, the rate of serum protection is high and very quick. After 2 doses, the titration will increase rapidly and the immunogenicity is very strong and very long lasting. And we introduced that the adult preventive vaccine. And on this slide, you can show some of our strategies of marketing. First one, of course, fast access to Asia Pacific region. Not only we got EU, U.S. licenses, and we also submitted 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 will find commercialization partners. We are also communicated with CD of China to make it clear our strategy for registration in China. We -- 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. And 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, is 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. So there's a very clear trait in the difference of the immunological harms. So earlier diagnosis, earlier treatment definitely will make a difference. And the standard treatment is to use the nucleus so that we can reduce the burden of the virus. We can use the natural immunological interferons 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 the big limitation, which is after using the interferons, they need to take the drug permanently. So for the Hepatitis B patients, we hope that we can develop some solutions, 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. So in order to have functional care -- 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 response -- spontaneous relapse. And with time goes and to reduce the cccDNA or eliminate cccDNA over time if they will sustain the immunological control and for a complete cure. On the left-hand side, we can see the life cycle of a virus from [indiscernible] entry, amplification and packaging and secretion of the antigen and it doesn't contain all of these whole viral genes or these cells. And because this kind of a surface antigens they lower the immunity or deplete the immunity, therefore, to improve the immunity, for example, innate immune responses and adaptive immune responses, that are so important. Therefore, the first candidates in the combination, well, 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. So, professor Hong mentioned that we have fewer products. The last one is BRII-835 and it will target all the siRNA. In the last 2 to 3 years, we work together with our partners in doing Phase I and Phase II trials in chronical hepatitis B. We can effectively degrade the viral transcripts and reduce the viral antigen levels, and we have administered the combination to 397 patients, we have a very good safety profile. The second solution is BRII-877 and the most potent surface antibody in reducing surface antigen and prevent the reinfection. And we have made some modification on the surface and not only increase their neutralization ability but also to improve their combination to the immunological cells. And we can effectively reducing the HBsAg. The last one is BRII-1. And I think this is optimize the recombinant vaccine and for the chronic hepatitis B. On this slide I can do a summary. In the past 2 years we did the single therapy trial of the 3 vaccines each -- 3 treatment each. And since this year, we have started to do some combination trials to see which is the best combination and here, what you can see is that the studies and trials we are doing, including the combination of BRII-179 and BRII-835 -- and the BRII-835 and PEG-IFN-alpha and also together with our partner -- sorry, our partner is doing the BRII-835, BRII-877 with or without PEG-IFN-Alpha, and we are also doing BRII-179 with PEG-IFN-Alpha. So later, we can elaborate more on the scientific strategy. And we have a small sample this trial carried out by our partner, which is the combination of BRII-835 and PEG-IFN-Alpha and our competition and their combination has a slight difference. And you can see that off-treatment data was presented at EASL in June 2023. And also at the APASL in February this year. And now I can share with you some highlights of our data and also some newly launched trials and the researches. The first one is combination of 835 and PEG-IFN-Alpha. The design has been shown to you before. So the design is answering some questions. So, all the siRNA are the control group, we want to see that whether we can improve the functional cure possibility. So PEG-IFN and at different time windows or we give the 2 treatment at the same time. 6 months or 12 months or at the same time, the siRNA and the PEG-IFN at the same time. At the early phase after the treatment, the result was very encouraging because the siRNA and PEG-IFN take a long time up to 48 months. The surface negative conversion rate is very encouraging, up to 30%. But I want to stress is that the trial was not limited to baseline surface antigen. We know that interferon works well is when it's less than @, but the baseline -- lowers the baseline, better is the result. But this study is open to all the patients. So you can see the negative conversion rates contains some patients 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 results. We clearly see some rebounds but many of them sustained the treatment effect, the negative status. And this was released in the 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 that the titer -- lower is the titer, higher is the possibility that the patient will have a rebound. And at least more than 100 or some of the patients more than 500 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 indicated to predict whether the patient will have rebound or sustained results. And interestingly all the negative conversion patients have antibody responses is different from only receiving PEG-IFN and converting to negative. Because the sample is small, we don't have comparison of interferon. So later, we can see that we did something more in follow-up study. And regarding the surface antigen. According to the requirement of clinical trial, we made some adjustments. They are very similar in previous studies and the [liver], after treatment of interferon and in the clearance patient with clearance of surface anti-[indiscernible] and if the titer is more than 100 units at the end of the CHB patients achieve HBsAg lost by PEG-IFN 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. The higher curve is higher than 100. And the increasing number of studies suggested that the presence of HBsAg, securities specific B cells in peripheral blood of CHB patient may be an important immunological indicator to predict the interferon treatment efficacy. So as the chart show this is the proportion of serum conversion in CHB patients receiving interferon treatment comparing the [indiscernible] -- positive group and the negative group. So for the antibody response and in our 2 studies to study the 179, we detected some interesting phenomena. The first thing is that the BRII, half BRII. You can see this structure as antigen and the BRII has to as one. The structure is very similar to the preventive vaccine. It contains a small antigen Pre-S2 and Pre-S1 antigens. So what is the difference? This is that for the purpose of treatment. Firstly, the concentration is higher. Secondly, it has been optimized in terms of the adjuvant. So it is a 3 antigen therapeutic HBV vaccine formulated the adjuvant bias [indiscernible] immune responses. We used 2 clinical trials to evaluate. One is a 4-week dose to evaluate the B-CELL and C-CELL -- T-CELL. We can see the specific T-CELL compared to the doses is elevated. We also observed that some chronic hepatitis B patients after receiving the treatment, there is a response of antibody. The proportion is change. You can see the blue columns. Another study combining 835 and 179 and because patients need to take the vaccination for 9 doses. So the effect is even more obvious. In this chart, we drove comparison for the only receiving siRNA, and we can see different titers represent different titers, more than 1,000 units, very high. And around 20% of the patients belong to the blue part. And the majority of the patients that means, more than 40% of the patient after the treatment, they can have more than 100 IU per limit per liter. We also found that some patients don't have antibody response after the vaccination. So according to the result of these 2 clinical trials and the PEG-IFN, especially for the sustained serum conversion after the treatment of interferon. We have a hypothesis that patients who illicit 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. And we can anticipate that people have different innate immunological responses. And some people after 1 dose, they have good response. Others even have taken many doses, they don't have a good response. So we want to tell the patient with good baseline immunogy from the -- those who don't. And in this way, the anti-HBs responders receive BRII-835 and has PEG-IFN-Alpha therapy can have improved functional cure. So 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 reaching for increased functional cure. So we will evaluate the hypothesis with [indiscernible]. 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 -- see, we already got the N.M.D approval from CDE. We will start the breeding trial of four 877. Firstly, you can see here, this is effective neutralizing antibody for with different status and this is the patient after treatment and they rely a lot on the doses. For it's patient, the [indiscernible] is very good. When it's less than 1,000 at the baseline, only 6-milligram can reduce 1 or 2 logs. And now there are more and more preliminary data, which are supporting further evaluation of the potential of 877 for functional cure in patients with chronic HBV infection. So 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. So in China, we are making big efforts to do the bridging study. And this is our partner Vir, which is doing a Phase II study. It is also called the MARCH study. It has 2 parts, Part A and Part B. So in the European liver conference, it is reported that at the end of the treatment, the results of treatments and the results at 48 weeks post-IoT. So firstly, we observed the PK and DMP to see whether it can be reduced. We can see different regimes, 75 or 80 milligrams. This is a fixed dose and siRNA in parallel or not in parallel, consecutive. And Cohort 3 at the end of the treatment, it reduced about 3 logs, and 90% of the participants achieved surface antigen less than 10 IU per [indiscernible] and at the end of the treatment. Because this is the short duration of treatment and all the HBsAg levels rebounded in all treatment groups, but remained almost 1 log below baseline and the safety profile is very good. And now reaching evaluating 24 or 48 weeks with the BRII-877 with or without having INF-alpha are going. So by the end of this year, we will publish the data. So before the end of my presentation, I will briefly stress our BRII's HBV cure strategy. siRNA plus PEG-IFN, according to the [indiscernible] design and the protocol, we can foresee a good [Audio Gap] outcome of treatment. Based on that, and the PEG-IFN, our partner is completing the Phase study. Meanwhile, we -- you can see there is second group of interferon alone and I also mean that as siRNA and the 179 patients because they have good immunological profile. So after the treatment, if these patients are called back to receive siRNA interferon so that we can evaluate the role of 179, weather it can improve the rate of cure. So we are planning and in discussion another clearer Phase II study design. 179 immunohiping plus 835 for PEG-IFN-Alpha. So in the next 6 months, you see some new clinical trial to be launched. So again, better evaluate different combinations, which can better improve the target cure rate. So some expected date, we will publish the clinical trial results. And in China, we will have Phase II study evaluate 179 on the patients who had been receiving PEG-IFN-Alpha, 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, 835 and 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 line execution for Mainland China and the APAC region. And regarding the combination -- regarding the life cycle of viral and other channels, and we are also doing a lot of work of translation and clinic evaluation. And based on the data and our deep understanding of the unmet need we will design our different strategies of combination. So 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 for your long-term support and attention, and thank you for giving me this opportunity to share with you. Thank you.

Thank you so much, Dr. Qiu, for your very detailed introduction from provision to functional cure. Just as Dr. Qiu shared each candidate drug for Hepatitis B developed the [indiscernible] not only have unique mechanism of action, but our best-in-class candidates. This gives us the opportunity to provide potentially the best treatment option for different types of Hepatitis B patients. Each program is designed based on the [indiscernible] of the patients. We have to -- and for the QA session, I can see that we are receiving many questions. But due to time constraints, we will take some frequent ones for [indiscernible] and Professor Dr. Drew you can also ask a question after the meeting.

Professor [Jon], I have a question for you. Within China, can reach the goal of eliminating Hepatitis B by 2030. What should we do to achieve that?

There are 5 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 treatment to 80%. This is the only way to reach the goal of incidents cutting by 90% and the death rate cut by 65%. We must work together to improve the diagnosis rate to 90% and treatment rate to 80%. This is a way for us to eliminate viral hepatitis by 2030. If we can not do it, there would be no way, because we are good at the other 3 [indiscernible] I think this is a recap but if we can expand the diagnosis and treatment we can do that. So pick up [indiscernible] here. If we cannot make these 2 goals, meeting 90% and 80%, we cannot meet the goal. If we can improve diagnosis to 90% and the treatment to 80%, we definitely can reach the goal of eliminating Hepatitis B by 2030, namely reducing the incidents by 90%, and death rates by 80%.

Dr. [indiscernible] , I have one question for you. Just elaborate more on this. PreHevbri compared to other marketed vaccines, what strength or advantages that's PreHevbri have. There are some newly launched 2-dose vaccines. So compared to that, what advantage do we have?

We haven't got the data. So the question is for Dr. Drew. Dr. Drew can you answer the question?

Yes, we have pivotal trial data. This is head-to-head to compare the second generation, the small surface amyloid protein of [indiscernible]. And because there are different components on the surface and the manufacturing mechanism, and the immunity is much higher. Therefore, in the head-to-head trial, we can see that immunogenicity is stronger and longer lasting and the titer is significantly higher, especially for the susceptible adults. So there is a newly launched to those adult vaccine. So if we only compare to the serum protection rate is similar, but I must say you have head-to-head comparison but the type of anti[indiscernible] and I think that PreHevbri has the advantage. And we, therefore, anticipate a longer lasting of protection.

Another question for Professor Drew. The question is that in your presentation, you said earlier prevention, earlier screening and treatment, all is important. And some of the audience want to know which are the challenges in China in hepatitis B prevention?

First, the newness without vaccination in 2019 to 2021, were vaccinated for the newness without vaccination when they were born and they were vaccinated during these 3 years. But the program was suspended up to 2021. So I think we should establish routine program to give vaccination to all the new names who had not been vaccinated when they were born. So 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 incidents because they have lower immunity to the virus and the patients 30%, 40% that are not immune to Hepatitis B. So 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 wanting to take hepatitis vaccination should have one because there are still some social stigma to these patients. And so anybody who are voting to receive the Hepatitis B vaccination should be vaccinated. And I think China is quite good. In the first dose vaccination is more than 90% for the newness It cannot be 100% due to very reasons. Some newness will miss the first dose. So it's difficult to get this score higher. And the 3 dose recognition is already 99%, no headroom for improvement. So for newness we are quite good and I think the headroom lies in the adult population. We will continue our vaccination scheme for newness. 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. So this is the way to expand the prevention and eliminate the hepatitis B. So expanding prevention is one solution. Expanding -- expanding prevention, expanding diagnosis, expanded treatment. So combining all the things together, we reach the goal set by [indiscernible] elimination of viral hepatitis.

Thank you, Professor [indiscernible] and due to time constraints, that's all for the Q&A session. From the introduction of Professor and Dr. Drew, we know that elimination of hepatitis B is always the mission of BRII Biosciences, let's joined government agencies to scientific research institute to pharmaceutical companies, and we can make this dream a reality. It has not only solve the physical pain for patients 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 this event is available at Brii Biosciences. [Statements in English on this transcript were spoken by an interpreter present on the live call.]