Good morning, good evening, everyone. Thank you for joining our AASLD Data Readout Investor Call today. Before we start, I would like to remind you that statements made during this call may include forward-looking statements. The company is not obligated to update these statements based on new information or events. This is Sarah Qiu, Associate Director of Investor Relations. On today's call from Brii Bio's Executive Management Team, we have Dr. Zhi Hong, Chairman and Chief Executive Officer, Dr. David Margolis, Chief Medical Officer, Dr. Qing Zhu, Head of China R&D, and Dr. Ankang Li, Chief Strategy and Financial Officer. Dr. Hong will provide opening remarks, followed by Dr. Margolis discussing our AASLD presentations. Dr. Zhu and Dr. Li will join the Q&A after the prepared remarks, and finally, Dr. Hong will close with final remarks. Now, I would like to turn the call over to our CEO, Dr. Hong.
Please go ahead.
Well, thank you, Sarah. Good morning, good evening, and welcome to this conference call. I know this is almost towards the end of AASLD. Some of this abstract was published on Friday. I wish we can share this information as soon as we could, but we're under data embargo from AASLD, so this is the timing of this press release, and this update conference call is the result of this data embargo. But nevertheless, I want to give you a quick update on this AASLD. I think this is truly a very exciting meeting that where we have seen a lot of things begins to come together.
As you know, the last five years, many, many companies, including ours, continue to invest, search for a cure for HBV. I think at this conference, a lot of Phase 2 data begin to read out. I think you can see, for those of you who have looked at the abstract, you will quickly understand that the entire industry has converged onto a number of very important directions, and those that focus on antivirals and those that focus on immunomodulators. Among the most promising antivirals are the siRNA or the antisense oligonucleotide. Among the immunomodulators, there's obviously data on pegylated interferon, TLR, as well as immune checkpoint inhibitors.
And also for the adaptive immunity, we've seen data coming out from a therapeutic vaccine, including ours. I have to say that where we are making a lot of progress, I think the journey to where we are today has truly been extraordinary. I can tell you from the data we have seen so far, I continue to support the direction of our HBV cure strategy. If anything, there's more data support the choice of our investment in this area, specifically, in BRII-835, the siRNA, and the BRII-877, the neutralizing antibody, and also BRII-179, the therapeutic vaccine.
Another very important thing that I want to let you know that together with our partner, Vir, we actually have 10 presentations at AASLD, and 4 of which are late breakers, making significant progress in both HBV as well as HDV. We would like to give you some brief update on our program, as well as some of the latest development from Vir, our partner's portfolio as well. So without further ado, I would like to turn this to our Chief Medical Officer, Dr. David Margolis, who will take you through on a deep dive in terms of what we have presented at this meeting.
And for those of you who you know who obviously appreciate that we as a multinational company have the ability to do this conference call in both English as well as Chinese. So for those of you who are willing to listen in the Chinese version, you're welcome to join us later after this hour, and then our head of R&D, Dr. Qing Zhu, will present you in Chinese the latest progress. So no worry if you don't feel comfortable in asking questions at this English session, you can wait until the Chinese session, or if you prefer to ask questions in Chinese, we can certainly answer your questions in Chinese. The executive team here are completely bilingual. So with that, I'm going to turn this to David. Please go ahead.
Thank you, Zhi, and I'm delighted to be able to walk you all through some of the data that we were able to share at the AASLD conference in Boston over the past few days. So as a reminder, Brii continues to have multiple clinical assets across a variety of therapeutic areas. Our hepatitis B approach includes three clinical assets, all of which are now in Phase 2 development. BRII-179, the therapeutic vaccine, for which we have global development rights, and our collaboration with Vir has allowed us to focus on Greater China development for BRII-835, the siRNA approach, and BRII-877, the monoclonal antibody approach. Next slide.
We continue to believe, and believe also that the data from this most recent conference suggests that combination therapeutic approaches are likely going to be necessary for us to achieve functional cure in hepatitis B. We're fortunate that we have access to multiple mechanisms of action, for which we can look at a variety of clinical approaches and combination approaches. BRII-179 is an optimized recombinant vaccine containing S, Pre-S2, and Pre-S1 antigen, and a viral-like protein. Has now been explored in three clinical studies. We'll share some immunologic data from one of the studies, in further slides, as well as some biologic efficacy data from another study. There have been over 180 subjects dosed, so we're starting to get a fairly good handle on the safety of BRII-179. BRII-877, of course, is a monoclonal antibody approach.
We'll also be sharing some evolving data from Vir with this compound, as well as with BRII-835. At a very high level, our clinical development program is shown at the bottom. The BRII-835 plus BRII-179 will show some evolving immunology data, both T-cell and B-cell data from that program. BRII-179 plus pegylated interferon will show biologic efficacy data from a late breaker abstract. BRII-835 plus pegylated interferon is an ongoing study where we continue to enroll to validate data that had previously been shown from the MARCH study. And then lastly, a triple combination with the siRNA, the monoclonal antibody, and pegylated interferon, is data that Vir showed at this conference. Next slide. So the abstracts that BRII presented are shown here, two of which were late breaker acceptances as posters, and the last, regular submission poster.
I'll walk you through each of these, but just as a reminder, we'll be looking at immunologic data, both T-cell and B-cell, efficacy data from BRII-179 combination with interferon, and pharmacokinetic data from siRNA, looking at regional differences. Next slide. First, we'll start with BRII-179 plus BRII-835. This is a study where safety and efficacy data has already previously been shared. We're gonna focus on the immunologic data from this study. As a reminder, we are looking at 1 arm with siRNA or BRII-835 alone, and 2 arms with BRII-835 in combination with 9 doses of BRII-179 therapeutic vaccine. Next slide. To the left, we'll focus on T-cell responses, and to the right, we'll focus on antibody responses.
It's important to note that most people believe to obtain functional cure, you likely need components from T-cell, humoral, and antibody responses to establish a durable cure. This data is important for us to help elucidate what type of immunologic coverage we have in the T-cell and the B-cell space, and we're learning more and more about each of these areas as we continue to look into our studies. Off to the left, we look at T-cell response by ELISpot, and the top row is looking at cohort A, BRII- 835 alone, and a combination of cohort B and C in the bottom row, BRII-179 plus BRII- 835. You can see to the left, minimal ELISpot response to Hepatitis B-specific antigens observed prior to dosing, and in the top column, some evolution of a Pre-S antigen response in the 835 alone treated subjects.
When BRII-179 is introduced, we see a significant increase in the breadth and the strength of a T-cell response, as noted by ELISpot, which increases over time and is notable for its reaction to a broad spectrum of hepatitis B antigens. To the right, we have previously shown some antibody data for shorter-term vaccine dosing, but here we can see evolution of the antibody response with significant strong anti-HBs responses elicited in some, but not all, chronic HBV patients and the evolution of that response over a continuous dosing. Similar kinetics were observed in patients receiving 4 or 9 doses of BRII-179, with or without 835. We believe that it's important that there are some individuals who are not able to fully elicit a response to 179, suggesting those groups of individuals may be immunologically incompetent to a response and less likely to respond to functional cure. Next slide.
So now we'll shift gears and look at the BRII-179 plus pegylated interferon study, with a focus on biologic efficacy and correlating the antibody data that we just saw with outcomes. In this Phase 2 proof of concept study in China, individuals with a hepatitis B surface antigen less than 1,500 were initially treated with interferon across both arms. The initial phase of this study involved assessing the hepatitis B surface antigen response to interferon, and individuals who had a partial response with a hepatitis B surface antigen between 100 and 0.05 were then eligible to be enrolled at study week zero to either receive 7 doses of BRII-179 or interferon alone.
In all cases, the interferon was then continued for further 6 months, so ultimately, all individuals received 1 year of interferon and 6 months of BRII-179 or placebo. The week 24 time point is the end of treatment time point, and week 36, which is also shown here, gives us 12 weeks of off-treatment follow-up data. Next slide. Firstly, the BRII-179 plus pegylated interferon combination was generally safe and well-tolerated. This is now our third study with BRII-179, and we did not identify any unique adverse events associated with BRII-179 during the conduct of this study. A fuller briefing of the safety is shown in the poster, which was presented at the conference. In the graph to the left, we're looking at hepatitis B surface antigen at the end of treatment, week 24 time point, and 12 weeks off of treatment, week 36.
The solid bars represent the intention-to-treat population, and the dashed bars represent the per-protocol population. In this particular study, the per-protocol population can be treated as an as-treated population. Because this study was conducted during the COVID lockdowns, a number of individuals did not receive the full course of treatment and therefore are more accurately represented in the per-protocol population. In both groups, a delta favoring BRII-179 was seen with improved rates of HBsAg clearance in the BRII-179-treated subjects. This difference was maintained and/or increased following 12 weeks off of treatment, as can be seen on the graph to the left. In the graph to the right, you're looking at hepatitis B surface antigen seroconversion, defined as hepatitis B surface antibody greater than 10 IUs per liter in combination with surface antigen loss.
Here we see strong correlation between antibody presence and use of BRII-179, linking that to surface antigen loss. In the next slide, we'll look at further details on the antibody response. So here we're looking on the left side at different titers, greater than 10 on the left side and greater than 100 IUs per liter on the right side. BRII-1 79 leads to significantly higher anti-HBs levels than interferon alone treated subjects for both titers. Between 40% and 50% of individuals are able to generate greater than or equal to 10 IUs per liter, and approximately 20% are able to generate 100 IUs per liter. In a multivariate logistic regression within this study, we established that the presence of antibody titer greater than 10 or greater than 100 was highly correlated and highly statistically significant with surface antigen loss.
Next slide. So now we'll turn to the BRII-835 pharmacokinetics data. This study continues our collaboration with Vir and helps us establish the pharmacokinetics data with siRNA across regions, inclusive of both APAC in the study on the left and China in the study to the right, with both single and repeat dosing. Next slide. Here we see similar PK profiles, whether or not individuals were enrolled in APAC or Mainland China, across two different dosing cohorts and statistically comparable systemic exposures, demonstrating the PK characteristics of BRII-835 in participants with chronic HBV infections in patients is similar to that reported from previous studies with healthy volunteers, and Chinese ethnic background from Mainland China had no apparent impact on pharmacokinetics exposures. This data will help us bridge from ongoing studies around the globe to additional studies which will be conducted within China.
Next slide. So our partners, Vir, also presented a number of data outputs from their programs, and we'll focus on the two at the bottom. This is looking at VIR-2218 and VIR-3434 siRNA plus monoclonal antibody with or without pegylated interferon for the treatment of chronic hep B. This is continuation of the March study, part B, which looked at various combinations of siRNA and monoclonal antibody. We'll also look at their data in chronic hepatitis D. Next slide. So firstly, we're looking at here the combination of VIR-2218 or VIR-3434, and its effect on hepatitis D, whether in isolation or in combination.
So you can see with each monotherapy agent, whether it's with 2218 or 3434, modest effects were seen in reduction from baseline and hepatitis D, with minimal number of individuals achieving below the level of quantitation or the limit of detection. However, when administered in combination, there was appeared to be optimal hep D antiviral activity, with 100% of patients achieving HBV RNA less than limit of quantitation and 80% lower than limit of detection. ALT safety was good in this study, with one individual having a transient ALT rise in the 2218 arm, but no individuals having ALT safety concerns in the combination. Next slide. Lastly, we'll look at the follow-up from the March study.
March study is a multi-cohort study looking at various durations and various combinations of VIR-2218, the siRNA, with or without pegylated interferon and with or without monoclonal antibody combination. Previously reported are various combinations of siRNA at various durations with pegylated interferon. I won't discuss that data in detail. We have discussed previously the far right column, which demonstrates that siRNA in combination with longer durations of pegylated interferon is able to achieve approximately 30% surface antigen loss rate. That's the data which prompted the additional follow-up study, which we're now conducting, exploring a larger cohort of siRNA plus pegylated interferon in a controlled fashion.
The new data shared by Vir at this study at this AASLD conference is highlighted in the purple and the blue columns, where VIR-2218 plus VIR-3434 for 20 weeks is shown in the purple column and in combination with pegylated interferon in the blue column. In both instances, surface antigen loss was observed at end of treatment in approximately 15% of individuals. What's interesting here is that the dual combination, without the presence of interferon, is able to achieve surface antigen loss rate comparable to that without interferon, suggesting the possibility of further enhancement for a pegylated interferon-free regimen. That, of course, requires further validation and additional studies. Next slide. So now taking a step back again and just focusing on our overall hepatitis B cure strategy.
We continue to believe that this will be an iterative process where multiple combinations are explored, and we feel that out of this conference has come a number of different important studies, which gives us confidence about our approach. We will be initially building on the Phase 2 results, which I've highlighted already, inclusive of 835 combinations with interferon and now BRII-179 combinations with interferon, to establish initial efficacy studies and confirmatory studies validating surface antigen loss in those populations. We'll then continue our collaboration with Vir and with others to optimize combinations for broader populations, targeting increased cure rates over time, 30%-60% range, and ultimately to tackle all hepatitis B patients, giving them access to potential curative regimens. It's likely that additional agents will be needed. Next slide. We continue to release data across a multitude of combinations.
Most of the data which I have just talked about is already highlighted here. And we're working in close collaboration with Vir to ensure that we optimize collaborative potential, particularly with BRII-179, where we're now establishing a biological effect correlated with the antibody and T-cell production, which we've identified following the dosing of BRII-179. We'll continue to share data as it evolves, but we really look forward to your questions and the discussion around the data which we've just shown.
Thank you, David. I think we're ready for questions. I will be trying my best to direct the questions, so let's open it up.
Okay, the first question is coming from Roanna, from Leerink. Roanna, please go ahead.
Hi, everyone. This is Rosa Chen on for Roanna Ruiz at Leerink Partners. Thanks so much for sharing your data. I'm gonna ask the questions in English, if that's-
Roanna, I think you're on mute.
Can you hear me?
Yeah. Now you're back.
Oh, okay. Great. This is Rosa Chen on for Roanna Ruiz at Leerink Partners. Thanks so much for sharing and highlighting your recent data.
I think we just lost the connection here. Roanna, maybe we'll go to the next.
No, no, she's, she's back. She's back.
Oh, she's... Okay.
... Go ahead. Sorry.
Can you hear me?
Yep, I can hear you. Go ahead.
Oh, okay. Okay, great. So in your Phase 2 interim study for BRII-179, seems like there were three treatment-emergent AEs that led to discontinuation of BRII-179, and then also some Grade 1 and 2 AEs. So can you provide some additional details as to what these AEs were, and is there a way to mitigate this moving forward?
Okay, I'm going to turn this to David.
Yeah. So the AEs that led to discontinuation were for proteinuria, pulmonary tuberculosis, pruritus, and an issue with gastric emptying. So these were not necessarily felt to be related to study product, but nevertheless led to discontinuation of dosing. And I don't believe we found a signal that was tightly associated with BRII-179 itself outside of ISRs, which were commonly reported with BRII-179 dosing, but there were no discontinuations to the ISRs. Most of the ISRs were considered mild or moderate.
Got it. That's helpful. And then a second one. So same study, from weeks 24 to week 36 of treatment, we saw that antibody titers continued to rise, but, S antigen loss slightly decreased, or it was kind of flat from weeks 24 to week 36. So do you have any speculations as to why? Since we typically expect the S antigen to decrease with the treatment duration, and then you see the signal with the, increased antibody titers, which is also positive.
Yes, I can start, and maybe others can comment. So I think, you know, this is probably the most critical finding from this study, establishing the correlation between the antibody-- presence of antibody and surface antigen loss. So I think while you're highlighting the persistence of the effect in the BRII-179 arm, what we think is actually most interesting here is that it's, it's very likely, given the relatively lower surface antibody titers that are observed in the interferon arm, that you may begin to see rebound. So the increasing delta that we're observing between week 24 and week 36 is essentially due to rebounding cases where the surface antibody may not be high enough to hold.
We're not necessarily expecting, although we could see some additional surface antigen loss, but I think the most important finding is going to be seeing whether or not we can maintain a durability of the response, or whether or not there'll be a rebound. And our hope is with the potent antibody levels we're seeing, that we'll be able to maintain that response over time.
If I may add just that there are nine patients seroconverted in the BRII-179 group versus one in the PEG interferon only group. There are five rebound between 24 weeks and 36 weeks. That's the 12 weeks follow-up. Four of them have no antibody response, and one of them have a low antibody response. Now, bear in mind, this is still a group-level blinded data, so we don't know specifically which one. We can only tell, you know, from a rebound data, whether or not they have antibody response or not, you know, at the group level. So this is not at a patient level, has not been unblinded yet. It's only unblinded at the group level.
Got it. Super helpful. And then one final big picture question. Do you plan to go forward with the Phase 3 using PEG interferon and BRII-179, or could you consider replacing PEG interferon with a different mechanism that is also an immunomodulator or an immunostimulant with maybe better tolerability? And, like, noteworthy that your partner, Vir, presented pretty compelling data showing the same HBsAg clearance with PEG and without PEG. So is that something that you could consider adding VIR-3434 to BRII-179? What are your thoughts on that?
Yeah. So these are indeed big, a big direction kind of question. We are very pleased with the versatility of BRII-179, because on one hand, we think we can use this to select patient, to enrich patient, and to identify patients who have a sufficient intrinsic and antibody immunity. On the other hand, we have shown with the PEG combination that it does generate functional antibody that can directly contribute to the clearance of surface antigen and more importantly, sustaining that surface antigen clearance.
There are obviously thought about, you know, if the if there's other agent can remove the surface antigen to to undetectable level, whether or not BRII-179 can be used as a booster to stimulate seroconversions and as a way to sustain the the clearance of surface antigen. So there's a lot of ideas that we're we're looking at that. Obviously, I think our immediate focus is to move on into some studies that that we will design in such that it will be definitively addressing some of these efficacy and safety endpoint. So we're in the process of engaging regulatory authority to determine what are the top 2 or 3 study that we like to move forward quickly.
I think clearly the goal here is to design the study to definitively address the efficacy and safety endpoint.
... Thanks so much for taking our questions. That's it for me.
Thank you.
We also have an offline question here on the competitive landscape. How to interpret the rationale behind the GSK deal? What's the difference between Brii’s siRNA and J&J’s, and if you can comment that, and if Brii has any HBV BD plan, and what's the strategy here? Thank you.
So it's our general practice that we do not comment on our, you know, competitors program unless it's already been published. So I think from the published results that we do know that in the J&J siRNA program, there's two siRNAs that targeting different site on the viral genome. I believe one of them is at the DR1, the other one is in the open reading frame of the S gene. And our antibody, our siRNA is a single trigger so-called single trigger siRNA that targeting DR2 region. So that's one difference that I can share with you. I think from the clinical data perspective, from all published data, I think all the siRNA and ASOs seem to produce the same reduction of surface antigens.
They all seems to be plateaued at around 2 logs, so maybe a little bit more than 2 logs. I think at the very beginning, it was a little bit confusing that people were seeing, you know, different log drop, and that's because the dosing regimen was very different. Some was given on a very short, a few doses, others are given multiple doses and for longer duration of time. But it's fair from all the study we have seen so far, pretty much for all the siRNAs, it seems to reach a plateau between 2.0-2.5, and I think that's. I don't think from a clinical perspective, there's no difference between the two siRNA programs. And we cannot really, you know, comment on, you know, why they do the deal.
I think, you know, clearly this is something that it may be better re-addressed by asking GSK directly the question. So I think that's hopefully answer your questions.
Okay. Thank you, Zhi. We will go next to David Guo. David, please go ahead.
Hi, can you hear me?
Yep. Go ahead, David.
Okay, great. Thanks, Dr. Hong, for this question opportunity or opportunity. May I ask something that is not really science related, but about the 3-antigen hepatitis B vaccine vaccines. Are there any updates from the discussion with CDE and other regulatory and any updates on that, please? Thank you very much.
I would direct this question to Qing, our Head of R&D in China.
For the, just for the 3-antigen hepatitis B vaccine, we submitted the Pre-IND, and we already had some discussion with CDE. So we're waiting for the formal meeting schedule in probably the early next year. I don't know if I answer your questions, and then this will let us know what is required to continue to work on 3-antigen hepatitis B vaccine to bring to the China market.
Okay, great. And do you have any expectations, like, the process ongoing, what kind of steps we may need to go through? Thanks.
No, not really. So that's why we're waiting for the meeting scheduled. But we did submit our clinical study design, so we were hoping to get some feedback on the study, so then we have a clear path forward what to do with the 3-antigen hepatitis B vaccine registration. Yeah.
Okay. Very clear. Thank you very much, Doctor. Thank you. Thank you.
We also have another questions on next steps on BRII-179, new combination trials. If we can have an update on that, and if there's any sequence or prioritization of launching BRII-179 in APAC and globally.
Yeah. So as I mentioned early on, we are considering multiple combination. One of the study we hope to start, and I think we have we are following regulatory document. We believe this is a sub-study of a ongoing study where we are calling back all the previous patient that have been exposed to BRII-179, that we know their antibody response and their antibody phenotype. So we believe this group of people will be important for us to bring them back and for a period of treatment in which we can then determine whether or not the antibody response-guided curative treatment is a option for further improving the functional cure rate.
So that study, we can start before the end of the year, and then, and hopefully, we can share this information after we complete a study. And that's one. And then we obviously consider a couple of other studies where in active discussion with the regulatory authority to make sure that we can align on the study designs, and then obviously, you know, this is, will take some time. But we are very excited about some of this program that we should be able to embark next year. And I think this is something that we're very excited about it. We hope to design the study to definitively, as I mentioned early on, address the efficacy as well as the safety endpoint.
So providing a very clear level of functional cure rate that we can anticipate. So clearly we have multiple POC studies as I mentioned this to you at the beginning of the call, that Vir, together with Brii, we are absolutely working on 5 or 6 different combinations and data continue to read out. And then from those readouts, then we can design the definitive study as a next step. So for those of you who've been following us for a while, that you know, it's right now, I think the time is here now for us to transition all our combination studies, treatment options into late-stage.
So all of them will be designed to definitively answer the question, with the right regimen and potentially the right patient population. So that's all I can say. I'm sorry that I'm a little vague because I can't really say too much without getting the alignment with the regulators, so that has to go first. I think somebody asked the question early on with what, with BRII-179, because we're holding the global rights, so that does give us the opportunity to, you know, talk about studies globally and either in partnership with our partners or new partners. And that's what we are trying to do.
So clearly, we're not gonna stop the BRII-179 program just in Greater China, and we're gonna, we're gonna expand that study globally. So more to come and, but I can't really comment anything in detail without having alignment or discussion with, with the regulators.
Thank you, Zhi. Okay, I think that concludes today's Q&A session. Now, I will hand it over back to Zhi for some final remarks. Zhi, please go ahead.
Well, thank you very much for joining us. I know there's a lot of data to digest, and I really appreciate all the support you have given us in the past. I think we, as a company, have gained a lot of insight through our own studies as well as our partner studies. I can categorically make the following comment. Hopefully, you agree. Compared to a few years ago, it's no longer a challenge for us to dramatically reduce the surface antigen level, and even to clear those surface antigens. I think we have the tools available to do that, and that including our program as well as our competitors' program. So that's one thing that's very, very important, that we have gained significant insight over the last five years.
The second insight that we have gained and we've learned in the past five years was in order to sustain the clearance of surface antigen, you must have immune, immunologic control. In this case, we have, again, significant knowledge with the insight related to the antibody response. Multiple study have shown that where if you have a strong antibody response, then you have a much better chance to sustain the clearance of surface antigen. And these are coming from a study that is done with siRNA as well as with pegylated interferon, so antibody response is very important. At the same time, we also know through our own study that where a broader T-cell response is also important.
In fact, in some of the study patient that we have seen in the BRII-179 plus 835, and those patients who have achieved loss of surface antigen, they have very robust antibody response as well as T-cell response. So we're very pleased to have a therapeutic vaccine, BRII-179, that allows us to broadly activate the T-cell response and then more specifically activate a strong antibody response in a significant proportion of patient. So we do believe that having both T-cell response and B-cell response are very important. However, given the variability and the challenge of doing T-cell response analysis, and it's not always easy to correlate with the T-cell response because it's very broad, it's variable.
With the antibody response, however, it's very easy to measure and it's very specific. So we believe, we have learned in the last five years, having a strong antibody response is highly correlative to the sustained clearance of surface antigen. So that's the second thing we learned. The last thing we learned is the challenge of curing HBV, mostly because the heterogeneity of the HBV patient, not only with regard to the surface antigen level at the baseline, also their intrinsic immunities. There's really not a very good way of telling through biomarker research in terms who has a stronger or more robust or more sufficient intrinsic immunity with regard to T-cell as well as B-cell, who does not.
And we believe, the three study we have completed or on the process of completing, have gave us a lot of insight, for a very unique opportunity to allow us to very safely, select patient who have strong, intrinsic immunity that most likely will respond. And then at the same time, allow us to spare others who probably does not have, sufficient, immunity, to be treated at this point. It's not to say they will not be treated in the future. Obviously, it requires additional, tools that, that has yet, to become available. So these are the three things that I can share with you, and I will continue to follow the landscape very closely and, and at the same time, and, invest in the direction that I just highlighted to you.
Number one is to enrich patient, to identify patient who are most likely to respond. Number two is to clear the surface antigen to the highest level we can with siRNA, a combination of siRNA and a neutralizing antibody. And lastly, is to, you know, generate robust antibody response and with this, with T-cell response together to sustain, the clearance of surface antigen. So, these are the direction that we have just laid out. I think it's becoming clearer now, compared to a few year... a couple of years ago, that in terms of where we're going. So I want to thank you all for your patience and for your appreciation of the work that we have done so far.
I really hope in the next 12 months-18 months, we're going to have some really exciting data to share with you. So stay connected, and I appreciate all your support. So at this point, I'm going to draw close to the call and then just remind you that we have a Chinese conference investor call that's coming up in about 13 minutes. I look forward to communicate with the latest results in Chinese with you. Thank you very much.
Thank you again for joining today's call. Goodbye.