Morning and evening, everyone. Thank you for your interest in Brii Bio, and welcome to participate our business update call. I would like to remind you that remarks made on today's call may include forward-looking statements. The company does not undertake any obligation to update any forward-looking statements, whether as a result of new information, further events, or otherwise. This is Chris, Company IR Director. I'm joined today by Dr. Zhi Hong, our Founder and CEO; Dr. Ankang Li, our Chief Strategy and Finance Officer; Dr. David Margolis, Chief Medical Officer; Dr. Susannah Cantrell, Chief Business Officer; Dr. Qing Zhu, Head of China R&D; Dr. Ellee de Groot, Chief Technology Officer; and Mr. Rico Liang, Greater China General Manager. A few hours ago, we just announced a VBI transaction, so joining me today, our senior management team would like to share more details regarding on the deal. After our presentation, we will open the call for Q&A. Welcome your question, conducted in Mandarin as well. I would like to turn the call over to our chairman, sorry, to our CFO, Dr. Ankang Li. Li, please go ahead. Thank you, Chris Fang. Hi, everyone. Thank you for listening and participating in our call. We are very glad that we just announced that we are broadening our leadership in the HBV field with a portfolio covering prevention to cure. We have extended our collaboration with our partner, VBI Vaccines. In this return, in the latest deal, we have obtained worldwide rights to BRII-179, which is a therapeutic vaccine for hepatitis B. Our exclusive license for BRII-179, which is VBI-2601, acquired by VBI, now is a worldwide market. We are going to establish our leadership position, not only in the HBV functional cure, but also we are extending to the prevention of the hepatitis B. In this deal, we also obtained the APAC ex-Japan rights to PreHevbri, which is a approved product in the United States and EU and a few other countries. We will have this exclusive right to develop and commercialize PreHevbrio in the APAC region. This is a best-in-class adult HBV prophylactic vaccine. The region include both APAC and Greater China. We are paying an upfront payment of $15 million, which include a few components, such as $5 million ring-fenced manufacturing supply, as well as $3 million equity investment into the VBI. VBI also announced its financing, its ongoing financing, which will be part of that $3 million investment. We will also pay VBI additional milestones and royalties based on future regulatory and commercial milestone events. Those payments are really backloaded. The transaction is subject to certain closing conditions, which, you can log into VBI's website to look at VBI's announcement. This is the highlights of the transaction. I think, with this transaction, we now covered HBV from prevention to cure, further expanding our leadership in this field. Thank you. I will turn to Dr. David Margolis, so that he can give you more highlights about two programs, as well as our plan to develop and commercialize them. Thank you. Thank you, Ankang. Our decision to invest further in BRII-179 is a data-driven decision based on our own data, as well as evolving data in the hep B cure space. BRII-179 is a 3-antigen HBV vaccine, which has been specifically formulated for use in chronic hep B patients as a therapeutic vaccine. We've conducted now two studies, and the interim data from both of these studies has been presented and is shared again here, which gives evidence that BRII-179 is able to induce both a specific hep B antibody and T cell response. The top study shows us that after four doses in NRTI backbone patients, BRII-179 is able to generate, in a large minority of patients, a substantial T cell and B cell-specific response. In the lower portion of the data, we can see that when combined with 835, and dosed for a longer duration of time, a more prominent response in more individuals was seen in both the antibody and the, and the T cell space. In fact, the majority of individuals were able to generate an HBV-specific antibody response, and in a majority of those individuals, the response was greater than 100 mIU/mL. Next slide. Why do we think that this antibody response is important and may be an important contribution to combination curative therapy? There have now been a number of studies, including this important study, which we recently presented at EASL, which have shown a correlation between the presence of antibody and the durability of seroclearance. In this study, individuals who were treated for up to 48 weeks with the siRNA BRII-835 plus pegylated interferon generated the highest rates of seroclearance, 25% at the end of treatment, 16% which were able to maintain seroclearance following the discontinuation of treatment. The important correlation that was noted in these individuals is that all four individuals with anti-HBs levels greater than 500 mIU/mL were able to sustain cure seroclearance, while all individuals with antibody levels less than 100 rebounded. Individuals with levels between 100 and 500 had a variable response. This suggests a very tight correlation between the presence or the ability to generate antibodies and the ability to maintain a durable seroclearance. Next slide. With this in mind, we believe now, and with the assumption of global rights of BRII-179, we have all of the tools that we need to evaluate the primary strategy of functional cure, which is the potent reduction of surface antigen, while at the same time promoting an immune response, which can help to maintain that seroclearance over time. With the use of the siRNA, which has demonstrated reduction in surface antigen levels in combination with possibly the monoclonal antibody, which is currently under study by Vir and is about to start a phase I study in China, along with the potent immune-inducing BRII-179, we believe this dual combination of surface antigen loss plus promotion of antibody production may help to maintain cure levels in the highest percentage of patients. We acknowledge that the patient population in HBV is quite variable, of great interest to us is to better understand these individual patient populations and identify those which are most likely to respond to these combinations. We plan to start multiple combination studies evaluating this premise over the next years, with the first studies to begin the second half of this year. Next slide. The cure for HBV is likely to be an iterative process. The field has learned a considerable amount of information over the last several years, we acknowledge this approach but also want to take advantage of it through our evaluation and the use of combinations to generate approvals in waves. Our first and primary approach is to take advantage of the data generated with BRII-835 plus pegylated interferon, showing sustainable cure in up to 16% of individuals in optimizing that combination, with or without BRII-179, to promote higher durable cure rates. In parallel, we expect to conduct combination studies, which will help us evaluate a broader set of patients and identify a subset of patients which can promote an even higher response rate, targeting cure rates in these subgroups, between 30% and 60%. Ultimately, we believe the field needs to get to a point where all patients with chronic hep B will have treatment options, and the data should help answer questions as to how to get there over time. Next slide. Now, moving on to PreHevbri. PreHevbri is a three antigen prophylactic HBV vaccine, forms the basis of BRII-179, but is formulated differently as a prophylactic vaccine. This is a well-differentiated prophylactic vaccine showing best-in-class seroprotection rates, antibody titers, as well as durability of these antibody titers over time. Recent data showing here on the bottom with antibody titers out to 3 and a half years. Next slide. We believe there is considerable opportunity to continue to evolve the prophylactic space. Obviously, hep B strategy, prevention strategies have been in place for many years, with national emphasis on increasing rates of immunization. In spite of this, low coverage of vaccination of at-risk individuals remains, with even young individuals with highest rates of vaccination superseded by falling rates over time in older individuals. There's also groups of non-responders to current vaccines which could be targeted, as well as waning vaccine immunity over time, all of which can be improved upon by a best-in-class vaccination strategy. Next slide. The unmet medical need is significant in the regions which we have now accessed rights from VBI for PreHevbri. This is an area of high endemic HBV infection. There are over 150 million individuals we estimate with hep B in the regions where we will be marketing PreHevbri. This presents an even higher number of patients that are potentially at risk in these high endemic areas, estimated to be up to 500 million. People, of course, living in these higher prevalence areas are at increased risk of infection. As mentioned on the previous slide, we believe there is considerable room for improvement in the vaccination rates and the penetration of vaccines in this market. Our access to PreHevbri will jumpstart our commercialization efforts as a company using this safe and highly efficacious vaccine. Next slide. This process will come in waves, with the commercialization happening in different countries at different speeds, largely based on the regulatory requirements for approval. The large global data set supporting PreHevbri will be taken advantage of in submissions to initially the APAC countries, which will be the first targets for commercialization based on the lack of need for additional clinical data, followed by a parallel effort to generate clinical data in China for access to the China market over time. Eventually, our hope is to increase overall market penetration and vaccine usage across the regions of interest, including, institutionalization into national reimbursement. The primary focus will be on self-pay markets. I believe this will take us to our Q&A. Right. Yep. I'll turn the floor over to Zhi Hong, our founder and CEO. Great. Thank you, David. Thank you, Ankang, for the summary of this transaction. Now I think we should open up for questions, and after Q&A, I will make concluding remarks. As Chris mentioned, you can ask questions in both Chinese or English. Feel free to do whatever you preferred. Thank you. Can we move to the next slides in the Q&A? Yeah. Thank you, Zhi. I think we have opened the line for question, and the first question is coming from Morgan Stanley, Jack. Jack, please go ahead. Please, operator, unmute Jack. Thank you. Hello. Hi, can you hear me? Yep. Hi, thanks, Dr. Zhi Hong and Chris for the question. I have two quick questions. It seems like, one, the next step, what the company will be evaluating would be the combination of BRII-179 plus BRII-835. Sorry, BRII-835 plus interferon-gamma, with or without BRII-179. I'm curious in terms of, one, what the implication. What the commercial implication, or I guess clinical, would be in terms of adoption for a three-drug regimen versus, I think, maybe previously we were kind of aiming for a two-drug regimen. Kind of how the dynamic would shift. Depends on affordability, depends on the administrative method, these consideration. Second one is, I see that kind of we're targeting a 15%-30% functional cure rate. I mean, that's a broader range, I think. How does that compare to kind of what previous regulatory discussion has indicated? You know, what was the threshold or bar that, say, CDE or NMPA would have considered to be a approvable threshold versus kind of what we're seeing based on the clinical updates that from Vir or from us and other companies in the past six-12 months? Just these two questions. Thank you. Well, thank you, Jack. I think those are excellent question regarding the next step. As David alluded to, that we now have significant knowledge and insight in terms of both, in terms of siRNA and neutralizing antibody, as well as the therapeutic vaccine 179. Those insight are very critical in terms of how we're gonna combine them and further optimize this. I think we have a starting point on, you know, although the sample size is small, at 16%, but we feel that's a good starting point for us to further optimize this, including how we're gonna select patient more carefully and then making sure that we always keep eye on not only losing the surface antigen, as well as enhance the antibody response. That, I think it's very important, shown by Vir's data as well as by many other people. I think with regard affordability issues, clearly that where, if we have a way to use two-drug combination, not three, then we don't have to do three. Obviously, when you don't have optimum response and then you need three, then you use three. I think, you know, pricing will not be the barrier for access. I think having a better cure rate, to me, is the most important driver for adoption of any HBV curative therapy. I think those discussion probably will be for another day when we talk about, you know, commercial strategies and, you know, more kind of in-depth discussing. As you know, that we're still a way from that. I don't think we should talk about affordability pricing strategy at this point. Your point are very well taken, and I think in China, we have always have to keep an eye on the, the affordability, and then especially, as I mentioned before, the cost of good consideration. As you know, that we're trying to make our regimen as efficient as we can to lower the cost of the good in order to be more competitive in this space. These are absolutely something that we're considering. With regard the FDA or EMA or regulatory or CDE and NMPA's current consideration of, you know, how to have these, how to define the cure rate and the percentage, the endpoint, I want to point to you some very helpful discussion as well as, you know, in the recent ENSURE study, as well as last year, there are a working group that looking at how to define, you know, the kind of a functional cure rate. The talk about in a more strict definition of sustained a loss of surface antigen, and there's also looser kind of understanding of, you know, maintain a very, very low surface antigen level post post-curative treatment over extended period of time. I think there are, there will be some publication, I think is coming up very soon. I do not want to, you know, foreshadow a lot of that discussion, but I would ask you to pay attention to in the near future regarding some of the publication on the consensus among EU- EMA and FDA, and then clearly those consensus will be important for China to consider as well. You know, obviously, the bottom line is that you have to start with a very good cure rate compared to the current standard of care, which is very low, from 3%-7%. Understood. Thank you. Okay, thank you. The next question is coming from SVB Roanna. Roanna, please go ahead. Great. Can you hear me? Yep. Great, thanks. I had a question on PreHevbri. I'm curious, what are the immediate next steps in China, and can you use the PROTECT and CONSTANT studies to support regulatory submission there, or will you perhaps need to run additional trials for it in China? Yeah, I think those are good questions. I mean, we're obviously with this deal, we're going to start talking to CDE and NMPA right away, and I know who we know who to talk to, and then we have already have some early regulatory assessment. I feel, Barbara, this is too early for me to comment on. This, there is a range of, as we can see from the past experience, there's a range of potential timelines in terms of regulatory requirement. I think there's something from the best case scenario of, you know, what we're seeing in the HBV vaccine from Merck and improving 9 days to some very long, you know, studies in the country. I think this is something that we'll find out pretty soon. There's clearly a significant need, as our GM potentially could answer some of the questions if you have more interest in this. You know, clearly, the country recognize this mRNA need. There's a large proportion of adult population has not been vaccinated, so there's the high-risk group has been identified. I think the current situation in China, this is a very open market with a lot of, very generic, vaccines, and then they all kind of similar to each other. The promotion is more from the vantage point of pricing. I think with a PreHevbrio, which clearly have been demonstrated clinically, without a doubt, it's a much better vaccine, much longer duration of protection and a strong antibody response and safe. I think this will help us to, you know, really promote this vaccine based on the information that we have. We think based on the need, based on the large population not being vaccinated and susceptible population, high-risk group, we think this is going to be a pretty important market. I think the other thing that I would say in a country, in APAC region, this is a high endemic population, high population density, high infection rate. I think vaccine as a business model is quite fit for those areas where, you know, the volume is big and the pricing is more affordable. We do believe this could offer significant advantage to addressing the HBV burdens in the various country and regions and with a very reasonable business model in this case. I don't want to say too much about this, other than to say we're still working this area, and then we're going to work with partners, with regulators and to figure out how we do this. This is probably what I want to say. Yep, understood. That makes sense. One more for me. Just circling back to your HBV combination regimen for functional cure, with A-35 and PEG interferon and with or without 179. I was curious, let's say your first test of this combination regimen, let's say everything works out well. Do you have any sort of sequence or prioritization of how you're thinking about launches in different countries, or how are you thinking about that? That's a good question. I think that's a good question. Obviously, our priority, our team is situated in China, that's where the action will be. I think our goal is to rapidly expand these various combination, testing them very quickly. As David mentioned, that we have a number of study planned, with the earliest one to start before the end of this year and to test the various combination. I think those are very important. With regard to the global rights, as you know, that we do have a partnership with the Vir, which has the option on a U.S. rights. Obviously we need, we will communicate with Vir regarding this opportunity and working together. I do think it's important for us to have the global right, because this will enable us to work more closely with Vir. I think as with before, that where we had to talk three parties in order to build a consensus agreement and to do it, and I think now it's more streamlined. I think we'll also appreciate that VBI understand that as well, and allowing us to, you know, form a much closer relationship with Vir, and then same time, free them to focus on the commercialization and manufacturing and supply of the PreHevbrio. Got it. Thanks for the color. Thank you. Thank you, Zhi and Roanna. The next question is coming from UBS, David. David, please be unmuted. Right. Thanks for giving me this opportunity. Can you hear me? Yep. I just want to follow up with if there's any further data that you could share with us about the combo therapy of BRII-179 and BRII-835, given that in February, we received that the data about this clearance. Also, post this deal, do we immediately take over any of the ongoing clinical trials of BRII-179? Are there going to be any and the expense impacts, going forward to us, please? Thank you very much. Okay, David, thank you for the question. I think with regard the data on BRII-179, and I want to point to our corporate update, that there are two events that we're going to share top line data for the two combination. One is the combination with siRNA, BRII-835. The other one is with the peg interferon. I think the data release you mentioned in February was just at the end of treatment with the first 50 patients, and then we had more data to come with all the patients and including some of the follow-up, the long-term follow-up of the first 50 patients. That information will come before the end of the year. We're also in the process of, you know, completing the study for BRII-179 combination with PEG-IFN. Then we're going to have to look at the data and unblind the data. I think those that will take some time. Also, I think this is going to be before the end of the year, we'll share some of the top line data. With regard to the clinical trial. Obviously, we're taking over the global development of BRII-179. That will, as I mentioned, that will free VBI to focus on commercialization of their prophylactic vaccine. With regard to our relationship with Vir, we hope this is going to provide even more, a closer partnership between us undertaking multiple combination, as we have done in the past, and perhaps, you know, in a greater geographic territory to test this combination. We're looking forward to have that conversation with Vir in the coming weeks and months. Hopefully we can have some to share in the next six months or also, and to see in terms of what else that we can do together. Clearly, this is a very important, very exciting news for us to expand our partnership with Vir. Okay, great. Thank you very much. Okay, thank you, David and Zhi. I received a written question regarding, can we recap the second half data readout regarding on the HBV pipeline? Zhi? What do you mean, recap the second half? Is there any, yeah, is there any catalyst for the HBV portfolio. Yeah. Next half of the year? Yeah. Okay. Thank you. I think we do. I think, I think Vir have updated everybody on the EASL at EASL study. you know, clearly, there's the MARCH study where they're testing the triple combination, the siRNA and the neutralizing antibody with or without peg interferon. I think the early study, the short treatment duration of the two combination, have clearly showed that there's a very universal reduction of the surface antigen, even in a very short period of time, and dropping everybody, almost everybody, 90% of patients to below 10 international unit per mL. that's a pretty important information that they have shared with you. They also said that towards the, before the end of the year, there will be more sharing of data on that combination with or without peg interferon for longer duration at the higher dose. Remember, the part A was at a suboptimal dose, is only 75 mg of the neutralizing antibody, so that dose will go up. I do want to mention that where the antibody, why we're excited about this, is that this is the only antibody we have seen so far, at 6 mg, have caused significant surface antigen reduction, more than a lot. I think people may have forgot more than a year ago. When data, when Vir showed the data, it was really exciting moment for people to think about neutralizing antibody. I know there's a lot of others and trying to develop neutralizing antibody. I really want to point out to the fact that this is the antibody that is so potent that we can offer to patient in a treatment cycle without pushing the dose really high beyond affordability. I think somebody mentioned early on about affordability. This is where we have to consider in terms of how we're going to position not only each combination of different asset, and also making sure that we have the right dose chosen that is actually that's going to make things more affordable to the broader patient population for the countries in China, APAC region. Thank you for giving you a long-winded answer to this. I hope I answered your questions. Yeah. Thank you, Zhi. As a reminder, analyst and investor, if you have any questions, please just raise hand. Thank you. Hi, Zhi also received a question regarding on the VBI transaction, noticing that we also supply chain investment and plus the financing. Can you give more color on that part? I'm gonna actually ask Ankang to comment on that. This is a pretty, you know, you know, comprehensive deal. I think there's different strategic intent with the different chunk of investment. I would ask Ankang to speak to that. Ankang? I guess Ankang is probably not let me try to answer your question regarding this. We have indeed made sure that we are making this investment, to ensure that we have the supply and manufacturing activity dedicated to supporting 179, as well as the early launch of PreHevbri. I think this is very important. As you know, many people probably have this commercial experience when you launch the product, oftentimes, you probably have seen other company you have invested, there's no supply available. This agreement is very important, and we bring finance that amount to ensure that once we launch the product in the region, there will be supply available and dedicated to us so that we can sell. I think that's what that is for the $5 million for the manufacturing supply efforts. The equity investment, I think the company obviously, right now given the market condition, is obviously at a very, I would say, stock price is low, so we're taking advantage of, you know, doing this and making sure that we're supporting them through our investment, at the same time, achieving return on investment. As you have noticed that from our previous investment at Qpex, and we have achieved $24 million of return on investment. I think as well as our other investment, we have always considered equity investment, because I believe this is something that if we make the right decision, we could win twice. I think this is always, has always been approach that we're undertaking with all the partnerships. We become a closer relationship with our partners, not only as their partners, as well as their investors. I think that helps to enhance our relationship in that regard. I'm sure that whether or not. I'm not sure whether or not I have answered your question, but that's basically what that is. Yeah, thank you, Zhi. Maybe coming another outlier question, because there is a celebrity in Hong Kong, just get suicide, over the night due to the depression. The investor is also curious about our CNS progress in the U.S., and especially for the major depressive disorder. Can you give a little bit color on that pipeline? Yeah, I'm glad you raised that question, and I think we're so shocked. Yeah. sad at the loss of Coco Lee. I think someone who are in the region, who, you know, will learn how to love. This is obviously illustrate a problem in our society, that where we know so little about it, and then we don't really have a good effective therapy to deal with it. I think I've mentioned this before, multiple time, with the COVID coming through, with a silent pandemic of mental health issues, clearly, this is one area that we are making major investment in this space. We believe this is gonna be the next wave of innovation. From a public health perspective, it's gonna be a hugely important area that require all of us to care about it. I think this is the kind of stuff where the news goes away. People just forgot about it. For most of us, you know, who are working tirelessly in this area, we recognize how many people are suffering from this, that including many of our own colleagues. This is not an uncommon disease. I think I can speak to that on behalf of a lot of people. I'm glad that you're paying attention to our mental health investment. I think this is a very important area for us to continue to invest and to address the significant unmet public health need. Thank you for the questions. Yeah, thank you, Zhi. The next question is regarding for the 179. Actually, the question is asked in Mandarin, they wanna get to know what is the competition landscape in China, especially in Greater China, about the prevention vaccine. How are we going to deal with that competition? That's a good question. 3 个 这 个 抗 原 组 成 的 这 个 疫 苗 ， 比 这 个 GSK 的 安 在 时 呢 ， 就 是 在 于 3.5 年 的 这 个 dose 那 个 follow up 的 时 候 呢 ， 还 有 这 个 将 近 5-10 倍 的 这 个 antibody 的 这 个 ， 比 这 个 安 在 时 要 好 5-10 倍 ， 这 个 就 关 于 antibody 这 个 ， title 。 我 就 是 说 从 现 在 来 说 呢 ， 市 场 需 求 是 在 那 的 ， 而 且 就 是 我 们 现 在 是 一 个 最 好 的 白 丝 巾 class 的 一 个 疫 苗 ， 那 我 们 有 ， 相 信 呢 ， 就 是 说 这 个 市 场 的 需 求 和 将 来 呢 ， 是 有 很 大 前 景 的 。 谢 谢 梁旭 。 呃 ， 对 ， 投 资 人 还 有 一 个 跟 踪 性 的 问 题 ， 就 是 这 个 预 防 性 的 疫 苗 引 进 之 后 ， 大 概 在 中 国 或 者 在 大 中 华 权 益 向 下 的 这 些 territory， 他 们 做 临 床 试 验 是 一 个 什 么 样 的 guidance， 或 者 我 们 的 这 个 计 划 有 什 么 比 较 ， 呃 ， 初 步 的 想 法 吗 ？ 这 ， 这 个 问 题 问 得 很 好 ， 但 是 我 想 现 在 我 们 还 是 ， 呃 ， 先 不 要 做 ， 做 过 ， 过 多 的 这 种 呃 ， 预 估 吧 。 所 以 我 觉 得 以 后 我 们 有 机 会 再 跟 大 家 分 享 ， 因 为 我 们 刚 刚 把 这 个 deal 做 好 ， 下 面 要 进 下 一 步 的 是 要 跟 CDE/NMPA 要 进 进 一 步 的 交 流 ， 等 我 们 将 来 已 经 有 了 这 种 确 定 的 这 个 临 床 的 计 划 ， 有 了 这 个 NMPA 的 guidance 之 后 ， 再 跟 大 家 分 享 可 能 会 更 好 一 点 。 但 是 我 就 想 补 充 一 下 ， 这 个 需 求 在 国 内 是 非 常 大 的 ， 那 么 在 这 个 ， 呃 ， 这 个 疫 苗 的 注 册 这 方 面 也 是 有 确 定 的 ， 这 些 一 些 ， 一 些 requirement， 这 些 我 们 会 进 一 步 跟 这 个 CD 进 行 ， 呃 ， 进 行 沟 通 。 但 有 一 点 我 希 望 大 家 能 知 道 ， 这 个 疫 苗 呢 ， 已 经 是 在 美 国 、 在 欧 洲 、 在 ， 在 英 国 、 在 加 拿 大 、 在 ， 在 以 色 列 都 已 经 被 批 了 上 市 了 ， 所 以 我 觉 得 这 里 面 还 是 有 很 大 的 这 种 ， 从 regulate 的 这 些 数 据 来 讲 ， 信 息 来 讲 ， 是 量 是 非 常 非 常 大 的 ， 所 以 我 觉 得 这 个 东 西 大 家 还 是 需 要 有 点 耐 心 ， 要 等 着 我 们 把 这 些 事 情 全 部 确 定 一 下 ， 再 跟 大 家 分 享 。 谢 谢 大 家 。 OK, 谢 谢 Zhi, thank you Zhi. The next question we notice Lawrence Wang, please go ahead. Lawrence can you hear us? 哎 ， 你 好 ， 你 好 ， 我 ， 我 想 用 中 文 提 问 ， 可 以 吗 ？ 哦 ， 可 以 ， 欢 迎 ， 对 。 你好，我 想 首 先 请 教 一 个 问 题 ， 是 关 于 Vir 他 们 做 那 个 siRNA 加 上 interferon 的 那 个 实 验 ， 他 们 当 时 是 没 有 用 interferon 做 对 照 组 ， 因 为 我 看 了 一 下 ， 他 们 实 验 只 有 用 siRNA， 单 独 用 siRNA 做 了 一 个 对 照 的 一 个 队 列 。 我 想 问 一 下 ， 你 们 后 面 会 考 虑 用 interferon 单 独 的 去 做 一 个 队 列 ， 然 后 进 行 对 照 吗 ？ 还 有 就 是 为 什 么 他 们 没 有 用 interferon 做 一 个 对 照 组 来 去 看 一 下 这 个 siRNA 具 体 的 一 个 效 果 是 什 么 样 的 。 然 后 第 二 个 问 题 是 我 想 问 一 下 ， 关 于 后 面 他 们 triple combination， 你 们 会 对 他 们 triple combination 能 降 ， 对 这 个 hepatitis B surface antigen 能 降 多 少 个 log， 会 有 一 个 预 期 吗 ？ 比 如 说 能 降 4 log， 或 者 甚 至 能 到 5 log 吗 ？ 然 后 第 三 个 问 一 下 他 们 triple combination 会 有 公 布 那 个 具 体 的 患 者 的 一 个 基 线 的 情 况 吗 ？ 入 组 的 一 个 基 线 情 况 吗 ？ 这 以 上 是 我 的 问 题 ， 谢 谢 。 我 先 试 着 回 答 你 前 面 2 个 问 题 ， 我 让 Qing Zhu 回 答 后 面 那 个 问 题 ， 因 为 他 可 能 对 这 东 西 了 解 得 更 多 一 点 。 Lawrence， 首 先 你 跟 我 说 一 下 ， 你 是 从 哪 个 firm 过 来 的 ？ 呃 ， 什 么 ？ 你 是 哪 个? 那 个 Z， 对 ， 我 们 看 到 他 是 在 中 国 本 土 的 一 家 ， 私 募 基 金 公 司 。 OK, 好, 谢谢. OK, OK, 我先跟你说一下吧, 就是说 Vir 的 study, 是, 这个 study, 它实际上是一个, 它对患者的选择, 从 baseline 来讲, 它是从 100 到 10,000 这么一个 baseline. 所以在这种 inclusion criteria 下, 用这个 PEG-IFN 做 control 的话, 是会有伦理上的问题. 这就是为什么它没有这个 control. 那至于我们下一步要走, 是不是要做一个 control, 这个是其实我们正在考虑的事情之中呢, 但是我们希望在不久的未来能跟大家分享一下, 对 吧? 就是说这要考虑到要有一个 control, 我们才能够正确地去回答这个 PEG-IFN 和 siRNA 他们 relative contribution 去这个 乙 肝 治 愈 的这个 结果嘛, 对 吧? 我前面曾经跟你说过, 在没有选择的人群当中, 这个 PEG-IFN 的它的 cure rate 大概在 3% 到 7% 左右, 对 吧? 这个会得到比较好的这种 control study, 这肯定是需要做的, 但是要在什么样一个范人群当中做, 这需要非常慎重地考虑, 从伦理上来进行一些, 跟监管机构进行交通, 交流的. 你说这个 triple combination, 就是你的意思, 实际上就是说, 就是这个 siRNA 加上 综 合 抗 体. 那现在看的在这个短期之内是要这个没到 optimum dose 上, 我们已经看到将近在 3 个 log, 对 吧? 这时间也比较短. 那在长的时间的话, 我们现在没有办法跟你分享这数据, 只是你只是有一个想象空间了, 在一个 optimum 的这个 综 合 抗 体 的 dose 下, 在一个 optimum 的 treatment duration 下, 如果再加上 PEG-IFN 的话, 这会是 4 个 log 还是 5 个 log, 这个东西我现在没有办法给你打包票, 但是我跟你说, 这不是一个. 不 能 够 达 到 的 一 个 goal. 很 多 病 人 他 进 来 ， 他 总 共 就 有 1,000 ， 比 如 说 1,000 个 international unit 的 话 ， 那 你 没 办 法 超 过 3 个 lock， 对 吧? 我 觉 得 就 是 说 还 是 就 是 要 看 ， 这 个 对 我 们 来 讲 非 常 非 常 高 兴 的 ， 非 常 excited 的 ， 就 是 说 其 实 这 3 个 drug 可 以 让 我 们 去 address 所 有 的 patient， 把 所 有 的 patient 都 非 常 的 universally， 把 他 这 个 surface antigen 表 面 抗 原 给 打 下 来 ， 这 是 我 们 看 到 的 一 个 最 好 的 一 个 数据 吧 。 随 着 我 们 的 数 据 不 断 的 成 熟 ， 会 有 更 多 的 这 个 结 果 跟 大 家 分 享 。 后 面 最 后 这 个 问 题 呢 ， 我 让 Dr. Qing Zhu 跟 给 你 们 分 享 一 下 。 季 ， 那 个 Dr. Qing 好 像 那 边 的 信 号 不 太 稳 定 ， 可 能 他 现 在 暂 时 无 法 进 行 回 答 问 题 。 那 好 ， 那 我 ， 我 ， 我 自 己 的 ， 我 现 在 其 实 我 现 在 没 有 ， 没 有 准 确 ， 对 于 它 这 是 一 个 MARCH study， 它 是 一 个 ， 一 个 ， 一 个 ， 一 个 platform trial， 所 以 它 的 inclusion criteria 应 该 是 consistent。 我 觉 得 我 现 在 没 有 办 法 给 你 确 定 ， 我 可 以 以 后 再 给 你 专 门 ， 通 过 Chris 给 你 提 供 具 体 的 这 个 baseline 的 level， 但 是 我 觉 得 应 该 是 在 100 到 10,000 左 右 ， 但 是 我 现 在 需 要 进 一 步 的 去 确 认 这 个 数 据 ， 这 个 ， 这 个 ， 这 个 information， 我 要 进 一 步 verify， 但 是 因 为 它 ， 因 为 它 是 一 个 platform trial， 我 觉 得 它 应 该 是 这 么 一 个 inclusion criteria。 Don't hold that against me. I will follow up, have Chris follow up with you on that specific question. I think it's broader baseline of 表 面 抗 原 。 谢 谢 洪 博 士 ， 谢 谢 Lawrence。 呃 ， 季 ， 我 们 现 在 没 有 收 到 更 多 的 问 题 了 ， 然 后 时 间 也 差 不 多 ， 因 为 即 将 九 点 半 开 盘 ， 所 以 您 看 您 要 做 一 个 closing remarks 吗 ？ Yeah, 好, 谢谢 大家. 我 知道, 大家 谢谢 大家 对 我们 公司的 关注. 作为一个 创新 企业 吧, 我们 实际上 是 一直 非常 坚定不移 地 去 address 很多 这些 global like public health 这个 issue. 我们 在 乙 肝 这 方面 肯定 是 公司 一个 非常 大 的 重点, 现在 也 看到 我们 通过 这个 VBI, 但 其实 我们 重新 consolidate, 我们 在 这个 乙 肝 这个 方面的 这个 投资, 从 预防 到 治愈, 这 对 公司 实际上 是 一个 非常 重要的 一个 transaction. 我 希 望 大家 能够 继续 进一步 跟踪 我们, 并且 support 我们, 我 觉得 我们 这 方面 是 非常 有 信心 在 这个 领域 进一步 地 去 引领 这个 整个 industry 的 这 方面的 这个 乙 肝 治愈 和 预防 这 方面 的 一些 非常 重要的 一些 新药 的 研发. 第二 点, 我 也 想 跟 大家 说, 作为一个 企业 来 讲, 我们 实际上 是 站在 一个 非常 好的 一个 战略 的 位置 上. We have all the insight from all the data that coming out of the mRNA, coming out of the neutralizing antibody and coming out of the 179 therapeutic vaccine. If I may remind you that as our data continue to mature, we actually expanding the safety population, the number of patients and subjects being exposed to the various modality. I think with those data further mature and we're gaining more and more confidence about the safety profile, then we know that we have the most potent neutralizing antibody by a long mile, and we're most advancing that. We have more than 200 subjects already exposed. We know we have the most advanced mRNA, then coming from the only innovator actually have commercialized mRNA as a therapy that's Arcturus. We absolutely have the best platform in this space. I think not with J&J and retaining the right to Arrowhead, I think the mRNA that we're working on is the most advanced mRNA at this stage. We also have the most potent vaccine of any kind to generate very strong antibody response. I think you have seen other vaccines that generating some T cell response. Obviously our vaccine also can generate that T cell response, when it comes to the antibody response, nobody even close to the ability of the virus-like particle that within the prophylactic vaccine and then 179, the ability to generate such a high level of antibody response. I think we have the best of all the modalities, we have the most comprehensive modalities, then that allows us to really, progressively, systematically test different combinations, and we're very confident that we have a lot more information to share with you. With regard the prevention, obviously this is a new area and new horizon for us that we tap in. Many of you have noted in the last two, three years that our effort to develop the antibody for COVID, this is the team that you're looking at, a team that has done it before, from discovery to commercialization. Even though the COVID situation has evolved, we have the manufacturing and commercial capability and understanding in terms of how we do this. To that, I'm very happy that this PreHevbri is coming in and fill that gap, then for us to start prep our engagement of the society, KOL and the commercial partners and things. Those are very important for the company. It shapes our strategy then further strengthen our commitment to addressing the HBV disease burden, you know, very broad, you know, very broad approach. I want to thank you all for attending this. I know this is a short notice. You probably still have a lot of questions, then please do send it to our IR and Chris, then we'll try to address this in a timely manner. We're probably also going to at the later time of this year, then to share additional information with you regarding our overall strategy of HBV. Stay tuned for that. Thank you very much! I'd like to close this meeting by thanking you and also thanking our partners at VBI, for really allowing us to create such a very comprehensive partnership and strengthen our partnership in the space. Thank you. 好 的，感谢 C 的结束 remarks。各位投资人，如果您有后续的问题，欢迎直接微信联系我，或者给我们的 IR email 写组邮件，IR@briibio.com 或者 Chris.fang@briibio.com。感谢大家的拨入，今天电话会议到此结束。You may now disconnected. Thank you.