Joining us today on a call from Brii Bio Corporate Executive Team, are Dr. Zhi Hong, Chairman and Chief Executive Officer, Dr. David Margolis, Chief Medical Officer, and Dr. Ankang Li, Chief Strategy and Financial Officer. Dr. Hong will begin with an overview of our strategic priorities and corporate updates. Dr. Margolis will review our HBV clinical programs, followed by Dr. Li, who will review our financial status. We will then open the call for questions. Now, over to our CEO, Dr. Hong. Dr. Hong, please go ahead.
Oh, sorry about that. Thank you, Kathy. Good morning and good evening, everyone. Welcome to our 2025 Interim Results Conference call. I am pleased to share with you our achievements in the first half of 2025. We made meaningful progress across our clinical programs while continuing to advance our broader corporate strategy. First and foremost, we advanced our core HBV functional cure program through multiple phase II-B studies. Data from the ENSURE study, particularly from Cohort 4, which we presented at AASLD and EASL early this year, offered encouraging evidence that BRII-179 can enhance anti-HBV surface antigen response and accelerate HBV surface antigen loss, two critical data insights that are helping to define our future combination regimens.
Running our two confirmatory studies in parallel is accelerating the evaluation of treatment synergies, enabling us to shape our late-stage development strategy based on the emerging data, bringing together a curative regimen. Based on the data insight from Cohort 4 of the ENSURE study that BRII-179 experienced participants achieved faster HBV surface antigen loss, we amended the protocol of our Enhanced study to evaluate a simplified combination regimen of BRII-179 and elebsiran plus PEG interferon, aiming at shortening PEG interferon treatment duration to 24 weeks from 48 weeks. At the same time, we continue to propel our other programs through internal innovation as well as external partnership. We outlicensed the Greater China rights of soralimixin mixing, formerly known as BRII-693, to ensure that our non-core program progresses efficiently without diverting our primary focus on HBV. We are also making ongoing investments in early discovery programs.
Our HBV program remains our top priority. We are working diligently to achieve a higher rate of functional cure. Our multi-MOA approach includes several phase II-B combination studies of our lead candidate, BRII-179, and elebsiran. The data we have seen so far in our ongoing study gave us the confidence that combining these assets may lead to a higher functional cure rate across a broader range of HBV patient populations. As we focus on HBV, we are seeking strategic partnerships to develop other assets in our pipeline, including the long-acting HBV candidates, BRII-732 and BRII-753. Most recently, we entered a license agreement with the Joincare Group for soralimixin and targeting multi-drug resistance and extended drug resistance gram-negative bacterial infections. The license covers the research, development, and commercialization of soralimixin in Greater China, where there is a growing threat of antimicrobial resistance.
Brii retains the rights of soralimixin outside of the Greater China rights and is looking for non-diluted funding and partnership opportunities. Our HBV functional cure strategy is built on three differentiated assets: BRII-179, elebsiran, and tobevibart, each targeting a distinct mechanism of HBV pathogenesis. Together, they form a multi-MOA platform designed to drive immune restoration, reduce viral persistence, and achieve a higher cure rate across the patient population. BRII-179, our proprietary therapeutic vaccine, has shown potential in priming HBV-specific immune response. Elebsiran siRNA works to suppress HBV antigen production, where tobevibart is a broadly neutralizing antibody and supports antigen clearance and then potentially HBV co-infection population. All three candidates have demonstrated an encouraging profile and have been granted breakthrough designation by CDE in China, highlighting their potential in treating chronic HBV infections.
Our partner, Vir Biotechnology has recently started the phase III program and is looking at elebsiran and tobevibart combination in treating HBV/HDV co-infection patient populations. Our clinical programs have collectively been studied in more than 1,600 patients. We now have three fully enrolled phase II-B combination studies: the ongoing ENSURE study, the ENRICH study, and the ENHANCE study, each strategically designed to optimize a sequential or combination regimen. These studies are essential in our effort to define a registration pathway forward with the goal of achieving the highest possible functional cure rate. A key insight emerging from our previous study is the potential of BRII-179 and for its ability to enrich and identify patients most likely to benefit from the curative regimen. Despite promising advancements, many HBV patients may not achieve a functional cure with the current therapy alone.
BRII-179 offers that unique ability to prime the immune response and help to distinguish responders to anti-HBV surface antigens. The induced immune response and identifying immune-capable patients may lead to a greater probability of achieving functional cure. In our updated data of Cohort 4 of ENSURE, at week 48, end of treatment, 61% of BRII-179 responders achieved HBV surface antigen loss compared to just about 10% of non-responders. Moreover, among all participants who achieved HBV surface antigen loss at the end of treatment, BRII-179-experienced participants achieved HBV surface antigen loss faster than BRII-179 naïve patients, among which 83% of BRII-179-experienced participants achieved HBV surface antigen loss within 24 weeks, compared to 55% of BRII-179 naïve patients. This result supports the potential of BRII-179 both as immunotherapeutics and also as profiling tools. It enlightens us to explore different combinations in our later confirmatory phase II-B study.
Particularly, the enrichment strategy can help optimize clinical outcomes while making more efficient use of healthcare resources. This approach is what sets our approach apart, not just stacking mechanisms, but using them to intelligently guide the treatment design and strategically deliver the right combination to the right patient population. With that, I will now hand it over to Dr. Margolis for a deeper look at our clinical program. David?
Thank you, Zhi, and hello, everyone. I'm pleased today to walk you through our latest clinical program focused on specifically our three phase II-B studies in HBV: the ENSURE study, the ENRICH study, and the ENHANCE study. These three trials collectively represent our multimodal strategy designed to deepen our understanding of HBV functional cure and define an optimized path forward towards registration.
Each of our three ongoing phase II-B studies builds on prior findings to explore distinct treatment combinations, advancing us towards an optimized development pathway. They are designed to assess additive or synergistic effects of BRII-179 and/or elebsiran and help identify the most effective combinations and responsive patient populations. Running these studies in parallel enables real-time learning, responsive trial design, and efficient advancement towards regulatory approval. As a refresher, the ENSURE study evaluates the contribution of elebsiran in driving functional cure in combination with pegylated interferon alpha. Cohort 4 of the study also examines comparisons between BRII-179 naïve and BRII-179 experienced patients, helping to inform sequential strategies and BRII-179's potential priming effects. The ENRICH study evaluates the role of BRII-179 as both an immune primer and a profiling tool to identify immune-responsive patients who may have a higher probability of achieving functional cure.
Lastly, the ENHANCE study includes two parts, two cohorts under the original protocol to evaluate a concurrent triple combination regimen of BRII-179, elebsiran, and pegylated interferon to enhance functional cure rates. An amended cohort was added based on the results coming out of Cohort 4, which suggested the BRII-179-induced immune response has the potential to prime patients to achieve faster HBV surface antigen loss, supporting a shorter course of pegylated interferon alpha. This amendment reflects our goal to reduce treatment burden while preserving efficacy in broader patient populations. Next, I'd like to further illustrate the latest update from each of these studies. At EASL 2025, we presented 24-week post-treatment follow-up data from Cohorts 1 through 3 of the ENSURE study and 48-week end-of-treatment data from Cohort 4, which was designed as a proof of concept for BRII-179's role in immune profiling.
The updated data from Cohorts 1 through 3 reinforced the key value of elebsiran in our HBV functional cure strategy. At 24 weeks post-treatment, elebsiran in combination with PEG interferon alpha achieved HBV surface antigen loss in 33.3% of patients in the 100 mg group and 21.1% in the 200 mg group, compared to just 5.6% with PEG interferon alone. These results further validate siRNA as a core mechanism in reducing viral antigen. We also observed that 83% of patients who achieved HBV surface antigen loss developed anti-HBs antibodies, most with titers exceeding 100 IU/L . This strong association between HBV surface antigen seroclearance and anti-HBs seroconversion reinforces that immune restoration is a hallmark to functional cure. In Cohort 4, patients were grouped based on their peak anti-HBs titers from prior BRII-179 exposure.
Either greater than or equal to 10 IU/L were classified as responders and less than 10 IU/L as non-responders. What we observed was a clear stratification of response. BRII-179 responders achieved a 61% HBV surface antigen loss rate at week 48 when treated with PEG interferon alpha plus elebsiran , compared to just 10% in non-responders. These findings support BRII-179's role as a potent therapeutic vaccine as well as a strategic tool for patient enrichment and immune profiling. By identifying patients most likely to respond to curative therapy, BRII-179 may help to personalize treatment decisions, optimize trial design, and ultimately improve cure rates while minimizing unnecessary treatment burden. A key insight emerging from our previous studies is the potential of BRII-179 to enrich and identify patients most likely to benefit from curative regimens.
Despite promising advancements, many HBV patients may not achieve functional cure with current therapies alone, and BRII-179 offers a unique ability to help identify patients who can better respond to these curative regimens. The identified immune-capable patients or the anti-HBs responders may have a greater probability, therefore, of achieving functional cure. In Cohort 4 of the ENSURE study, the immune profiling and potentials of BRII-179 are both observed. As I just shared, the immune-capable patients were identified through peak anti-HBs levels induced by BRII-179 in previous studies, and they achieved higher HBV surface antigen loss compared to the non-responders. In addition, we found that among all participants achieving HBV surface antigen loss at the end of treatment, BRII-179 experienced patients achieved faster HBV surface antigen loss than those that were naïve to 179.
83% of BRII-179 experienced patients achieved surface antigen loss within 24 weeks, compared to 55% in BRII-179 naïve patients. These results support the potential of BRII-179 as both an immunotherapeutic and as a profiling tool, and it enlightens us to explore different combinations in our later confirmatory phase II-B trials. Particularly, this enrichment strategy can help optimize clinical outcomes while making more efficient use of healthcare resources. Such maneuvers set our approach apart, not just looking at multiple mechanisms, but using them intelligently to guide treatment design and strategically to deliver the right combination for patients. The ENRICH study is designed to prospectively validate our enrichment approach as well as the priming effects of BRII-179. Patients receive BRII-179 as an immune primer, followed by combination therapy with elebsiran plus pegylated interferon alpha.
The aim is to determine whether immune responders identified via BRII-179-induced anti-HBs production have a higher likelihood of achieving functional cure. As an innovative development approach, this study allows us to better characterize the immune profile of chronic HBV patients and potentially identify those patients who are most likely to benefit from intensive treatment regimens. Meanwhile, in the ENHANCE study, we're taking the next step of evaluating our comprehensive triple combination regimen. The two cohorts under the original protocol assess whether adding BRII-179 to the elebsiran plus PEG interferon alpha combination can drive additive or synergistic benefit. In addition, the new cohort under the amended protocol aims to shorten the pegylated interferon alpha treatment duration from 48 weeks to 24 weeks in BRII-179 prime patients by evaluating a new triple regimen cohort with BRII-179 and BRII-835 combination treatment, followed by this added shortened course of pegylated interferon alpha.
In July 2025, we completed the participant enrollment of this amended cohort. This amended design is based on the findings from the ENSURE Cohort 4, which suggested that BRII-179 can induce robust immune responses that allow the patients to take a shorter course of pegylated interferon alpha to achieve cure. This approach provides alternative treatment options to satisfy differentiated clinical needs. To summarize, given the heterogeneity of HBV patients' immune profile and the critical role of the immunotherapeutic in the combination regimen, the ENRICH and the ENHANCE studies each explore a unique dimension of the role of BRII-179 in combination treatment. This framework enables us to define an optimal regimen to mitigate risks in late-stage development and to generate a rich dataset to guide regulatory engagement.
We have engaged with CDE and NMPA on potential phase III study designs and primary endpoints, and those discussions will continue following phase II data readouts. Running these trials in parallel has allowed us to iterate rapidly, test hypotheses in real- time, and adapt protocols based on emerging data. We believe this multimodal parallel approach is critical to solving the complexity of HBV cure and bringing forward the most effective regimens. Looking ahead, we expect several key milestones to shape the next stage of our HBV program. In the second half of 2025, we plan to report 24-week follow-up data on Cohort 4 of the ENSURE study. End-of-treatment data from our ENRICH and ENHANCE studies are expected to be released in the first half of 2026. These upcoming results will guide our potential registration development pathway and further define different combination treatment regimens to maximize clinical benefit.
I will now hand over to our Chief Strategy and Financial Officer, Ankang Li.
Thank you, David. Thank you all for joining this call. As a reminder, the financial figures I will review today are in RMB unless otherwise noted. We maintain a strong cash position with sufficient funds to support our operations through 2028. As of June 30, 2025, our bank deposits and cash and cash equivalents were RMB 2,075.3 million, representing a decrease of RMB 338.1 million, or 14% compared with RMB 2,413.4 million at the end of 2024. The decrease was primarily due to the payout of daily operations and research and development activities. Our other income was RMB 28.1 million in the first half of the year, representing a decrease of RMB 42.8 million, or 60.4% compared with RMB 70.9 million for the six months ended June 30, 2024.
This was mainly due to a decrease in banking interest income of RMB 21.6 million, attributable to the decreasing interest rates on Chinese Yuan and Hong Kong Dollar time deposits, and reallocation of short-term deposits to money market fund investments, and a decrease in income recognized from PRC government grants. We effectively controlled our operational costs through disciplined pipeline prioritization and organizational streamlining, while maintaining continued investment in core programs during the first half of 2025. As a result, our research and development expenses for the first half of the year declined by 7.3% to RMB 117 million, from RMB 126.2 million for the first half of 2024. The reduction reflects decreases of RMB 6.4 million in third-party contract costs and RMB 3 million in employee costs.
Administrative expenses were RMB 58.2 million in the first half of the year, declining 26.0% compared with RMB 78.6 million in the first half of 2024. The decrease was primarily attributable to decreased employee costs of RMB 9.5 million and decreased facility-related costs and professional service fees of RMB 8.4 million, which was primarily attributable to organizational optimization and effective cost control management. Our solid financial footing allows us to advance our HBV program into late-stage development while continuing to invest in early discovery efforts that support our strategy of pairing internal innovation with external collaborations. This balanced approach positions us to drive sustainable growth, deliver long-term shareholder value, and broaden patient access to meaningful treatment options. This concludes our prepared remarks. We will now open the call to your questions. Kathy, please go ahead.
Okay. Thank you, Ankang. We will now open the line to Q&A. If you have questions, please click raise hand in the webinar controls, and we will prompt you to unmute yourself. Hi, you are on mute. Please introduce yourself, and you can start asking questions.
Hi. My name is Michael Ahn, for Roanna Ruiz from Leerink Partners . My question today is, given the encouraging 61% seroclearance rate in BRII-179 responders from ENSURE study Cohort 4, how are you thinking about patient enrichment strategy moving forward? Will you consider a biomarker-driven approach to identify the 179 responder earlier in the study? How might this impact your phase III study discussions with NMPA? Thank you.
Thank you, Michael, for the question. I'm going to defer this to our CMO and David Margolis to answer this question. David?
Yeah, thanks, Zhi, and thanks, Michael, for the question. Yeah, we see the data from Cohort 4 as very insightful and very encouraging. It's clear to us that BRII-179 has the potential to categorize chronic HBV patients into these immune-responsive and immune-nonresponsive. That's now been observed in our preliminary studies with 179 where we observed the effect, and now we see the consequence of that, where the efficacy appears to be higher in that subgroup of patients. We are keenly interested in understanding how to bring that forward through phase III trials, and we are in discussions with regulators about the possibility of doing that. As you said, that might include evaluation of the anti-HBs levels in those patients that are pretreated with 179. That's something we're exploring as a possibility. We're not exclusively looking at the responder versus non-responder. We're also looking at the totality of the response.
One of the key insights that we expect to get from the ENHANCE study is looking at this triple combination of 179 plus elebsiran plus PEG interferon as a unique combination, but also looking at the priming aspects in the amended cohort, as we mentioned. I think both strategies are still alive, and we have been in active discussions with regulatory authorities about phase III design to evaluate that question.
Great. Thank you.
Thank you, David. Yeah, Michael, great question. Just want to add one more thing. Where we're looking at those biomarkers, we're also looking at those harder-to-treat populations, i.e., those patients who have high baseline surface antigen, to see whether or not we could potentially have a combination to benefit those patients more effectively as well. Good question. Thank you.
Thank you.
Dear investors, if you have any questions, please click raise hand in the webinar controls, and we will prompt you to unmute yourself. While we are waiting for more questions to come in, I will help ask some of the offline questions. What's the company's view on the competitive landscapes considering recent announced initiation of phase III registration trials of (Inaudible) ? What's the company's view on the AZO pathway and siRNA pathway?
Yeah, I mean, I think it's pretty exciting to see there are other treatment modalities becoming available and going after HBV patients. I think the early data from the antisense results have been encouraging, and longer-term follow-up will be an important data point for us to look at and evaluate in terms of how the new competitive landscape is shaping up. Many of you also know that GSK is finishing up a phase III study with bepi, the first antisense oligonucleotide that has the same sequence as the one that we just talked about, I think, from (Inaudible) . It will be interesting to see how that study reads out, and that can give us a way to, through similarity, try to figure out how that could potentially shape up with the other, the second antisense oligonucleotide.
With regard to the difference between antisense and siRNA, I think GSK has done a lot of work in this area where they demonstrate that in addition to the antiviral response, they also have been able to boost immune response through engagement of tRNA. I think they have shown some clinical evidence and also some ex-label studies to support that notion. For siRNA, on the other hand, I think it's perhaps mostly focused on antiviral activity rather than some of the tRNA engagement. That's really the only thing that we can see as the difference between the two, although in a broader sense, they both are targeting RNAs to degrade them. In the overall methods of action, it similarly falls into the RNA interference kind of categories, but there are nuanced differences between the two. That's probably why you see the difference in the clinic.
I have to say the most important thing is to focus on the final cure rate. We've seen the data from bepi in several of the phase III studies. It has a pretty impressive end-of-treatment response and then subsequently lost those responses due to HBV surface antigen rebound. It would be very critical for us to take a look at the (Inaudible) data, hopefully towards the end of the year. Thank you for the question.
Thank you, Zhi. There's another question asking about that. Recently, the China CDC launched a new reporting system, which will link the confirmed diagnosis of certain infectious diseases, including HIV and HBV, to those individuals' identities and enable a nationwide tracking of the reported cases. With this reporting system, the diagnostic rate of HBV may significantly improve. How do we assess the potential impact of this policy? Let's say if there will be an increase in treatment demands?
I think that's a broader effort from society, and it's always a challenge of treatment access. Just because we have a good therapy, that doesn't mean the patient will benefit from it. I think diagnosis is just the first step to really identify patients who are eligible for treatment. We think that's a good direction, a good step towards that. The other thing we also have been, we think it should also be done, as we have mentioned early on, is the awareness and discrimination. What comes with the diagnosis should also, at the same time, have an active campaign against stigma. We believe some of these are tightly related to each other, where you can increase the diagnosis without removing the stigma that may not be effectively increased diagnosis or access to treatment. We believe this is a very positive development.
I think that will help to increase the diagnosis rate, hopefully at the same time improve the disease awareness without the stigma. This is definitely a positive development. We're hoping this is going to benefit the patient in general. Obviously, more patients will get cured through the new treatment modality.
Thank you, Zhi. Let's see if any additional questions are coming in. Dear investors, if you have any questions, please click raise hand in the webinar controls, and we will prompt you to unmute yourself. As there are no more questions raised, this concludes the Q&A portion of today's call. Now, I will turn the call over to Zhi for the final remarks. Please, Zhi.
Thank you, Kathy, and thank you, everyone, for joining the conference call. I think we're very excited to see the development of new treatment modalities for HBV and functional cure. This has been the company's focus for the last six or seven years. We do believe, as a company, we have invested quite significantly in blazing the trail and trying to figure out how to better benefit HBV patients and provide a curative regimen to them. The company continues to believe that the program we have established has value to the future combination, either within our own combination or with others. We believe this is something that is very, very important for China, as more and more patients will benefit from the new treatment. I truly appreciate the investors' support in the past seven years and many new investors who are joining us in this effort.
I just want to thank you all for your support and your patience. We think in the near future, we'll be able to fully reveal what would be the most differentiated treatment regimen that will benefit the broadest patient population in China. That remains to be a goal for us. Thank you for participating in this call. Have a good day and good night.
Thank you all again for joining us today. We look forward to keeping you updated on our progress. Please feel free to reach out to us via ir@brii.com email address. In the meantime, with any further questions, goodbye.