Good day, everyone, and thank you for standing by. Please note that today's call is being recorded. This is Sarah Cho, Associate Director of Investor Relations. Welcome to Brii Bio's Interim 2024 Earnings Conference Call. Before we start, I would like to remind everyone that today's discussion may contain forward-looking statements, which involve risks and uncertainties. Actual results and outcomes may differ materially from those discussed today. These statements reflect our views only as of today and should not be relied upon as of any subsequent date. We disclaim any obligation to update such statements. Joining us today from Brii Bio's executive management team are Dr. David Margolis, Chief Medical Officer, and Dr. Ankang Li, Chief Strategy and Financial Officer. Dr. Li will begin with an overview of our strategic priorities and corporate updates.
Then Dr. Margolis will review our clinical programs, followed by Dr. Li, who will review our financial status. We will then open the call for questions. Now over to our CSO and CFO, Dr. Li. Dr. Li, please go ahead.
Thank you, Sarah. Good morning and good evening, everyone. Welcome to our 2024 interim call. It's a pleasure to share the progress we have made, particularly in our pursuit of a functional cure of hepatitis B, and to provide our outlook for the remainder of the year. Our mission at Brii Bio is clear: to develop a functional cure treatment option for hepatitis B, where we believe there is substantial opportunity to create a meaningful therapeutic impact for patients both in China and globally. As the global burden of HBV remains vast, with 254 million HBV-infected people according to the World Health Organization (WHO) 2024 Global Hepatitis Report, released in April. Our efforts are concentrated on advancing a combination of therapeutic approaches to potentially offer curative solutions.
In collaboration with our strategic partners, we are advancing a robust portfolio of HBV candidates that leverage our expertise in antiviral and immunomodulatory therapies. We believe our pipeline uniquely positions us to lead in the HBV space with three differentiated candidates: the siRNA, and elebsiran or BRII-835, the monoclonal antibody, tobevibart or BRII-877, and BRII-179, our therapeutic vaccine. These assets, each potentially best in class, are being tested in various combination regimens designed to enhance functional cure rates. All three of these HBV candidates have been granted breakthrough therapy designation by the Center for Drug Evaluation, or CDE, of the China NMPA, National Medical Products Administration. This designation acknowledges their potential to deliver substantial advancement over existing therapies and expediting their clinical development and regulatory review.
While concentrating our resources on HBV clinical programs to maximize impact, we are also seeking partners to further develop our non-HBV programs. We know that HBV functional cure is achievable in patients with low surface antigen levels, although the exact mechanism remains unknown. Our combination approach, utilizing surface antigen lowering therapies and immune modulation therapies, aims to enhance the effectiveness of HBV treatments and achieve better functional cure outcomes. Last year, we initiated our phase II INSURE trial, which investigates the addition of elebsiran to pegylated interferon alpha compared to pegylated interferon alpha alone. This study is now fully enrolled, with top line results expected by the end of this year. In June, we completed a phase I study of tobevibart in China.
This study builds on our partner's work and provides more data on Chinese patients, specifically by comparing human PK data between mainland Chinese subjects and those from other APAC regions and Europe. Encouraged by the recent data readouts and insights, we are motivated by the potential to find therapies with high cure rate for broader patient population. We are advancing all three candidates with additional trial planned for later this year. Our Chief Medical Officer, Dr. David Margolis, will dive more into our recent findings shortly. All three of our HBV candidates have now been granted breakthrough therapy designation from China NMPA, with tobevibart and elebsiran most recently receiving this designation in May. These recognitions, along with the encouraging data we have presented at AASLD and EASL conferences this year, reinforce our confidence in our combination strategy for achieving a functional HBV cure.
We have shared key data sets that for the first time demonstrate a direct correlation between immune responses induced by a HBV therapeutic vaccine and the reduction of HBsAg, along with sustained immune control of HBV infection. These data sets are guiding our current and future studies as we work to validate this data and gain further insights that we believe could lead to high cure rates. Notably, recent data from our partner Vir's MARCH and SOLSTICE study, presented at recent conferences, highlighted tobevibart and elebsiran's ability to achieve robust reduction of surface antigen and loss of surface antigen during the 24 weeks of treatment, with or without pegylated interferon alpha among HBV patients, and also 100% virologic response rates among HBV patients. Earlier this year, we entered into agreements with VBI to secure BRII-179 clinical supplies and better control future manufacturing.
Brii now possesses BRII-179 clinical supply necessary for all planned studies in the next two- three years, and continues to work on obtaining the relevant manufacturing capabilities. Despite recent updates from VBI, we remain confident that their situation will not materially impact our HBV cure programs. Looking ahead, we expect several critical data readouts from multiple phase II studies in the fourth quarter. These include early top-line results from our ongoing INSURE study, which is investigating the combination of elebsiran and pegylated interferon alpha in APAC regions and mainland China. In addition, we expect findings from our partner Vir's MARCH Part B study, which evaluates the addition of tobevibart to a regimen of elebsiran, with or without pegylated interferon alpha, as well as the previously mentioned SOLSTICE study, which evaluates tobevibart alone or in combination with elebsiran for the treatment of HBV infection.
With that overview, I would like to turn the call over to Dr. David Margolis, who will provide more details of our clinical programs. David?
Thank you, Ankang, and hello, everyone. Today, I'd like to update you on our clinical programs and highlight some of our recent hepatitis B data, which we presented at the EASL conference in 2024 . Let's start with a brief overview of our HBV assets, which spans multiple approaches to tackling HBV infection. Our assets include the siRNA, which directly targets and silences all HBV viral transcripts, a neutralizing antibody against HB surface antigen, and a therapeutic vaccine designed to trigger HBV-specific immune responses. Elebsiran, previously known as BRII-835 or VIR-2218, is an anti-HBV RNA, siRNA, targeting all HBV RNA transcripts with extensive clinical data from over 570 human subjects. It was designed based on Alnylam's siRNA platform, the only one that has been validated through multiple commercial launches.
Tobevibart, previously known as BRII-877 or VIR-3434, is a very potent, broadly neutralizing antibody that was shown to reduce HBsAg by one log with only 6 mg sub-Q dosing. It has a safety population of more than 350 subjects. BRII-179 has been investigated in three phase Ib and phase II studies, with a safety population of approximately 180 patients. It was shown to induce strong anti-HBs antibody responses and broad T cell responses in HBV-infected patients. We now have multiple phase II HBV clinical trials underway in Greater China, testing various combinations involving our three assets, as well as peg interferon alpha. Simultaneously, our partner, Vir, is conducting two phase II combination studies with elebsiran and Tobevibart, the MARCH and SOLSTICE studies.
Now I'd like to review the data we presented at the EASL Congress in June as a late breaker for BRII-179 in combination with pegylated interferon alpha. We showed data from our phase II study of BRII-179 and pegylated interferon alpha as combination therapy in adult Chinese patients that reiterate the strong safety profile of BRII-179 and suggests the ability to improve overall HBsAg loss rate in combination with pegylated interferon therapy. All participants here were HBeAg-negative, non-cirrhotic and virally suppressed, who had previously received 24- 28 doses of pegylated interferon alpha, resulting in HBsAg levels between 0.05 IU per mL- 100 IU per mL at screening. 114 participants were randomized, one to one, to receive either BRII-179 40 mcg or a placebo every three weeks for seven doses.
Alongside pegylated interferon alpha, 180 mcg subcutaneously with 24 weeks of treatment. The control arm received a placebo of peg interferon alpha on the same schedule and dose. After the end of treatment at week 24, participants entered a follow-up period for NRTI discontinuation monitoring through 48 weeks. During this time, we closely monitored their eligibility for discontinuation of NRTIs. Participants with an ALT level less than twice the upper limit of normal, HBV DNA levels below 10 IUs per ml, alongside HB surface antigen levels below 0.05 IUs per ml for two consecutive visits between 12 weeks to 24 weeks post-treatment were considered for NRTI discontinuation. Our interim analysis data includes all participants who discontinued NRTIs after completing week 24 of the NRTI discontinuation monitoring period, as well as those who withdrew from the study prematurely.
The data shows a 57% improvement in overall HBsAg loss rate in patients treated with BRII-179, plus pegylated interferon alpha, compared with the placebo group. This improvement was sustained from the end of treatment to at least 24 weeks post NRTI discontinuation. Additionally, a higher percentage of participants in the BRII-179, plus pegylated interferon alpha group had anti-HBs levels greater than or equal to 10 IU per liter and greater than 100 IU per liter compared to the placebo group, and the treatment was generally safe and well-tolerated, with no new risks identified in the post end of treatment follow-up period. Importantly, no participant with an anti-HBs antibody titer greater than 100 IU per ml at the end of treatment experienced HBsAg reappearance.
This suggests that robust antibody responses against HBV are necessary for sustained HBsAg loss off treatment, and the addition of BRII-179 to pegylated interferon can achieve sustained virologic response and enable NRTI discontinuation in chronic HBV patients, marking another step forward in our understanding of chronic HBV treatment. Moving on to our phase II trial combination of elebsiran and BRII-179. A robust immune response involving both T cells and B cells is widely recognized as crucial for achieving a functional cure for chronic hepatitis B. The additional data we presented in June from our phase II randomized trial show important first time direct evidence that immune responses induced by a therapeutic vaccine are associated with HBsAg reduction and viral control.
Moreover, they suggest the addition of BRII-179 to elebsiran induce substantial HBV-specific B and T cell responses, inducing neutralizing anti-HBs antibodies and breaking B cell immune tolerance that correlate with antiviral effect in a subset of patients with chronic HBV infection. On the left side of this graph, we observe T cell responses measured by ELISpot. Cohort A, shown in the top row, received 100 mg sub-Q dose of elebsiran alone. Below, cohorts B and C received elebsiran combined with 40 mcg of BRII-179, with cohort B also receiving a coadjuvant dose of 3 MIUs of interferon alpha. Initially, before dosing, there were minimal ELISpot responses to specific antigens. Over time, in cohort A, we see gradual development of the primary S antigen response with siRNA alone.
In contrast, when the therapeutic vaccine, BRII-179, is introduced in cohorts B and C, there is a notable increase in both the strength and diversity of the T cell responses. This response becomes more robust and extensive over time, covering a broad range of hep B-specific antigens. On the right side, the data illustrate the evolution of the antibody response over time. Previously, we had presented short-term vaccine dosing data, but here we see a significant anti-HBs response in several chronic hep B patients. This response continues to evolve with ongoing doses. Similar response patterns were observed in patients receiving either four or nine doses of BRII-179, with or without elebsiran. It is important to note that while some did, not all individuals were able to fully develop a response to BRII-179.
These data provide important insights into our understanding of our treatment's immunologic coverage and show that elebsiran and BRII-179 combination therapy elicited pre-S1 specific T cell responses and Th1 type cytokine responses with anti-HBV activity. First, we identified a pre-S1 specific T cell response targeting a region adjacent to the NTCP binding site. This response was associated with high levels of HBs surface antigen reduction in a subgroup of participants receiving the combination elebsiran plus BRII-179. Our ex vivo analysis also detected pre-S1 specific Th1 type cytokines, particularly IL-2, in participants with significant HBs surface antigen reduction, with no Th2 response observed in these patients. BRII-179 also demonstrated robust anti-HBV neutralizing activity, especially in participants who showed high levels of HBs surface antigen reduction and HBs surface antibody induction.
This adds to our increasing body of evidence that BRII-179 may have the potential to break immune tolerance and stimulate a functional HBV-specific immune response, which is a crucial aspect that will help guide us in our strategies to achieve a functional cure in chronic hepatitis B. Both data sets are very encouraging as we progress our clinical trials. To summarize our data from APASL and EASL 2024, this data continues to support the potential of our HBV assets. At AASLD 2023, last November, our BRII-179, combined with pegylated interferon alpha, showed a remarkable improvement in HBsAg loss and seroconversion rates compared to placebo plus peg interferon at week 24. These positive outcomes were sustained through week 36, reaffirming the robustness of that clinical data.
In another late-breaking presentation, BRII-179, in combination with elebsiran, elicited significant HBs antibody responses, particularly in participants receiving nine doses versus four. We also observed broad T-cell responses, further validating the immunologic potential of this combination therapy. We also have a few updates to share on our other programs, where we continue to seek partners to advance their development. For our multidrug and extensively drug-resistant gram-negative bacterial infections program, last month, we submitted an IND application for a phase I PK bridging study with BRII-693 in China, to support a global phase III registrational trial in patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia.
In HIV, our oral once-weekly compound, BRII-732, remains phase II ready, and we also have BRII-753 as part of the long-acting subcutaneous injection regimen, which could potentially be dosed every month to every six months. For our CNS program, we have completed a phase II U.S. study with BRII-296 in patients with postpartum depression, and we have also completed a phase I study in healthy volunteers with BRII-297, our long-acting injectable for anxiety and depressive disorders. We expect to report out data in the fourth quarter of this year. Lastly, our partner, AN2 Therapeutics, reported top-line results from its phase II clinical trial and further confirm the discontinuation of phase III development of epetraborole for treatment-refractory MAC lung disease.
AN2 continues to investigate further development opportunities for this compound, and we will keep you updated on any significant developments or next steps as they arise. With that review, I will now pass the call to Dr. Ankang Li. Ankang?
Thank you, David. As a reminder, the financial figures I will be reviewing today are in RMB, unless otherwise noted. We ended the first six months of 2024 with a strong cash position, sufficient to support our R&D and operations through the end of 2027. As of June 30th, 2024, our cash and cash equivalents, bank deposits, and restricted bank balance were RMB 2,477.8 million, compared with RMB 2,661.4 million at the end of 2023. The decrease was primarily due to payout of daily operations and research and development activities. Our other income was RMB 70.9 million for the first half of 2024, representing a decrease of RMB 15 million or 17.5%, compared with RMB 85.9 million for the first half of 2023.
This was mainly due to the decreased income recognized from government grants. Through pipeline prioritization, resource optimization, internalization of certain clinical development activities, and cost saving measures of third-party contractors, we have effectively controlled our operational expenses. Our research and development expenses were RMB 126.2 million for the first half of 2024, representing a decrease of RMB 76 million, or 37.6%, compared with RMB 202.2 million for the first half of 2023. 36.6 million of the decrease was attributable to the decrease in third-party contracting cost, whereas the decrease in employee costs contributed 36.4 million of the total decrease.
Administrative expenses were RMB 78.6 million for the first half of 2024, representing a decrease of RMB 24.2 million, or 23.5%, compared with RMB 102.8 million for the first half of 2023. The decrease was primarily attributable to the decrease in employee costs by RMB 21.7 million, which was primarily attributable to pipeline prioritization and workforce reduction in non-core areas. The company expects to grow in the core areas supporting the HBV cure program. We expect our current funds to be sufficient to support our development needs as we advance our HBV program through 2027 and look to partner our other promising candidates. We look forward to delivering continued shareholder value as we advance innovative therapies with the goal of broadening choice and access for patients. This concludes our prepared remarks.
We will now open the call to your questions. Sarah, please go ahead.
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. We will go first to Roanna with Leerink. Roanna, please go ahead.
Great. Thanks, everyone. So, quick question on your expectations for the phase II INSURE trial top line coming later this year. What are you hoping to see, both on the efficacy and safety side? And what would motivate you to keep moving forward into later-stage trials?
David, do you want to take that?
Yeah. Thank you, Roanna. This study is important for us in several ways. As you know, this is an evaluation of the siRNA plus pegylated interferon dosing. And it's also a controlled study, so it has a control arm of pegylated interferon. The key objectives from this study are to evaluate 100 mg versus 200 mg. As you know, we've prioritized 100 mg dosing of the siRNA for the China market. The first key data set for us is going to be validation of the dosing regimen. 100 mg, we expect to perform similarly to 200 mg, validating both as potential options. Because this study has a control arm, it's also very key to help us understand the individual contribution of the siRNA.
So the individual effect size of siRNA versus interferon will be more clear with the comparative data set, so the degree and scope of that change will be important as we make decisions about our combination regimens. Lastly, as part of the INSURE study, we're also looking at a fourth cohort, which is evaluating the BRII-179 pretreatment. That's a subset of patients previously treated with BRII-179 and BRII-835 and looking at their subsequent response. But that will be important to inform our pretreatment strategy with BRII-179. So as this data rolls out towards the later end of this year, we think it will be key in helping us to better design our later-stage trials.
Got it. Very helpful. And second question from me, I was also curious, how have your interactions been so far with the China regulatory authorities around HBV? Is there anything different in terms of what might be required in China versus in the U.S.?
We're very obviously appreciative and validated with our data sets in achieving breakthrough designation status for really all three compounds. This has enabled us to have more rapid, effective, and efficient conversations with CDE. We think it also reflects the prioritization that CDE has placed on HBV development, so they're very invested as well. It's a major public health challenge in China. At this point, we don't have any reason to believe that the regulatory path would be substantially different globally versus in China. We are actively engaged with them to make sure that we develop and design studies moving forward that are effective in answering the right questions and ultimately can lead us to approval.
Got it. Thank you.
Okay, let's see if we have more questions here. We have offline questions here on our discovery team. How's your discovery team under new leadership shaping the direction of your R&D programs, particularly in the HBV space? Are there any new strategic initiatives or areas of focus under consideration? Ankang, do you want to take that?
Sure. Yeah, so now we have a new team that we are, I think we are focusing on looking to the adjacent base that's relevant or related to our existing programs. We'll try to leverage our knowledge and expertise, and try to expand to certain new areas. But these are very early efforts, so we don't expect to have anything to attain it in the next two years from our discovery effort.
Okay, thank you, Ankang. All right, I guess that concludes the Q&A session of today's call. Now I will turn the call back to Dr. Li for his concluding remarks.
Right. Thank you, everybody, for joining today's call. We appreciate your attention and ongoing support. We're building on what we know so far, where we have already gained important insights into how to sustain HBV surface antigen loss, and how patients respond in different subpopulations with a number of ongoing trials. The studies that are going on right now will tell us even more, and we are starting new studies to give us more data as we look at comprehensive immunologic coverage and responses with sustained HBV surface antigen loss. Our resources are focused on HBV, and along with our partners, we are making a lot of progress that can help a lot of people. The assets we have, our team, and our ability to execute our programs are all very strong. They put us in a great position to succeed.
We have a lot of ambition and are highly motivated to find a cure. I'm confident we have the right strategy and capabilities to do it. While we look for an HBV cure, there are a lot of other great programs that are ready to partner and can bring additional global value in our quest to reduce disease burdens in large markets with heavily unmet patient needs. Again, thank you for your ongoing support, and we look forward to speaking with and bringing you more information as our data unfolds later this year. Thank you.
Thanks, everyone, for joining. If you have further questions, please don't hesitate to contact us at ir@briibio.com. Goodbye.