Morning and good evening, everyone, and thank you for standing by. Welcome to Brii Bio's full year 2022 earnings conference call. Our full year results announcement can be found on the investor relations section of our company website. At this time, all participate are in a listen-only mode. After the speaker presentation, there will be a Q&A session. Please be advised that today's conference call may be recorded. This is Chris Fang, Director of Investor Relations. Joining us today on the call from Brii Bio's executive management team are Dr. Zhi Hong, Chairman and CEO, Dr. Li Yan, Chief Medical Officer, and Dr. Ankang Li, Chief Strategy and Financial Officer. Dr. Hong will first provide us an overview covering our strategic pipeline priorities and business developments, followed by Dr. Yan, who will review our clinical programs in China and in the U.S. Dr. Li will go over our financial status.
We will then open the call for questions, at which time we will be joined by Dr. Susannah Cantrell, Chief Business Officer, Dr. Eleanor de Groot, Chief Technology Officer, Dr. Qing Zhu, Head of China R&D, and Dr. David Margolis, our Infectious Disease TA Head. Before we start, we would like to remind you that today's conference may be contained forward-looking statements which involve several risks and uncertainties. Actual results and outcomes may differ materially from those mentioned in today's announcement and this discussion. In addition, any forward-looking statements represent our view only as of the date of this recording and should not be relied as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I will now turn the call over to CEO, Dr. Hong. Dr. Hong, please go ahead.
Well, thank you, Chris. Good morning, good evening, and welcome to everyone joining our call today. It is great to be here and to share our progress in 2022. Our clinical program have progressed significantly. We have refined our key area of focuses, which will further drive our clinical programs in 2023, 2024. We have taken deliberate steps to align our pipeline priority with operational capacity to tackle the public health challenges more efficiently through breakthrough scientific innovation and critical patient insight. Through in-house discovery and strategic in-licensing with global best-in-class partners, this year we have made important progresses across our pipeline of more than 10 differentiated infectious diseases and Central Nervous System diseases.
In terms of leadership, we have expanded our expertise with key hires, many of whom I have introduced on our last call in August. This individual brought a wealth of knowledge and experience to our senior management team, positioning us for long-term growth and success. Looking at our pipeline, our programs have delivered exciting results, and with encouraging data read out from early to late stage trials that demonstrate the potential of our therapeutic candidate to address the broad range of infectious disease and CNS disorder. As we move forward, we are focused on two lead programs. First, in China, we are developing a functional cure for chronic hepatitis B virus infection or HBV infection, a condition that affect millions of people worldwide, and with the greatest disease prevalence in China.
Second, in the U.S., we are developing a first-of-its-kind therapy for postpartum depression or PPD, as well as major depressive disorder or MDD, which has significant need for new and innovative treatment options. We are excited about the prospect to make a meaningful impact for those patients who need desperately a better option to treat their conditions. For HBV, our goal is to develop a novel first-in-class and best-in-class therapies to achieve a higher rate of functional cure for chronic hepatitis B patients. As we work to bring curative therapeutic modalities through clinical development in China, our U.S. partner, Vir Biotechnology and VBI Vaccines, are leading development activities outside of China.
We are encouraged by the data generated today for BRII-835, a siRNA, and BRII-179, a investigational therapeutic vaccine, and other immune modulators, which suggests that the combination of HBV surface antigen reduction agent and the immune modulators are key to achieving a higher functional cure rate. Together, these assets have the potential to be part of the functional cure regimen for chronic hepatitis B infection. Additionally, in July, we exercised our option to in-license BRII-877, also known as VIR-3434, a potent and broadly neutralizing monoclonal antibody against HBV. Each of our candidates has very unique therapeutic modality with a proven clinical mechanism of action, which allows us to continue to explore different potential combination treatment in China for various patient group.
In the U.S., our primary aim is to develop BRII-296 for anxiety and depressive disorder, with a specific focus on postpartum depression and major depressive disorders. Our unique approach in this disease area leverage patients' experience and insight, which is the key differentiator in this significantly underserved disease category. Chronic antidepressant treatment are associated with a range of side effects, adherence issue, stigma, and concerns of not being able to get off treatment. Our goal is to offer a treatment disruptors or paradigm-shifting single treatment options that will enable patients to make easy decision to be on and off treatment. In our efforts to support maternal mental health, we are continuing to invest in patient research and advocacy to address patients' need and then preferences.
Our people-centric strategy, which supports meaningful engagement with leading mental health advocacy group, was introduced earlier this year to further this goal. Currently, we are working closely with the US Food and Drug Administration, or FDA, to align and agree on a PPD treatment protocol in preparation for our phase II proof of concept site. We are also developing protocols for study in MDD patients. Moving on to our HIV pipeline. We selected a new clinical candidate last year, BRII-753, a novel low-volume subcutaneous injection therapy with the goal of extending the dosing schedule to once monthly, to once quarterly, or even twice yearly. As stated previously, we are seeking partners to collaborate on BRII-732 once weekly oral therapy, as well as BRII-753.
The two compounds that show great potential, as key components in the long-acting HIV treatment regimen, or as monotherapies for HIV prevention. In 2022, we commercially launched the amubarvimab and romlusevimab combination for the treatment of COVID-19 in China, which has been well-received by physicians. Although COVID-19 is not the focus for us anymore, this experience is very valuable to ourselves, to our team, and it has proven our ability to quickly bring innovative drug to the market.
As a result of the constantly evolving COVID-19 trends, including the upcoming aspiration of the COVID-19 emergency authorization by the US Department of Health and Human Services in May 2023, as well as protracted regulatory inspections at our CDMO site, we have made a decision to discontinue the COVID antibody combination program and has stopped manufacturing effort.
We are working with US FDA to withdraw our application for EUA at appropriate time following the completion of activity required by the regulatory authority, and also with China NMPA to withdraw our BLA in the third quarter of 2023, once all the necessary regulatory requirements have been completed. We gain valuable insight working with the Chinese and the US regulatory agency, which we aim to apply to our future clinical program. With that overview, I would like to turn the call over to our CMO, Dr. Yan, to provide a more detail of our clinical program in China as well as in the U.S. Li, please go ahead.
Thank you, Zhi. Greetings, everyone. We have come a long way in a short period of time building a world-class R&D enterprise with a singular goal: to serve patients who experience high unmet medical needs, limited choices, and a significant social stigma. As Dr. Hong mentioned earlier, we are developing a broader pipeline of therapeutic candidates focusing on infectious and CNS diseases. We're leading clinical developments with potential first-of-its-kind treatments for PPD and for MDD in the U.S., and functional cure of hepatitis B in China. First and foremost, we have a diverse portfolio of HBV assets with different mechanisms of action, from direct turning off all HBV viral transcripts by siRNA to neutralizing antibody against the surface antigen and to therapeutic vaccines to spur HBV specific antibody and T-cell responses. This extensive pipeline gives us a strong competitive advantage and it demonstrates our unwavering commitment to addressing HBV.
We recognize that antiviral and immunomodulation targets are critical for the success of HBV therapy. As a result, our development approach entails conducting multiple combination studies, leveraging synergistic and complementary mechanism of actions to tackle this complex disease. Our goal is to identify and develop optimal regimens that provide a high functional cure rate for HBV patients with different physio-physiological characteristics. Currently, we have two ongoing combination trials. The first is a phase II study of BRII-179, a therapeutic vaccine in combination with BRII-835 and siRNA. Last month, we presented the interim findings of this trial at Asian Pacific Association for the Study of the Liver. The second trial is also a phase II study evaluating BRII-179 plus peg interferon. We have completed the patient enrollment last December for this trial, and we expect top-line results to be available in the second half of this year.
The interim analysis of the first 50 patients we presented at APASL last month demonstrated that BRII-835 and the BRII-179. This combination was safe and well-tolerated and was able to induce stronger antibody responses against the hepatitis B surface antigen. This combination led to improved HBsAg specific T-cell responses when compared with either BRII-835 or with BRII-179 alone. All cohorts of patients achieved the HBsAg reduction at the end of treatment with a mean decrease of 1.7- 1.8 log international unit per mL. In addition, two participants in a combination cohorts achieved the maximum reductions in surface antigen at or below the lower limits of quantification by week 40, along with robust surface antigen specific antibody and T-cell responses.
We expect to report additional data from this trial in the second half of the year while we complete the follow-up of all participants. While we conduct studies in APAC countries and regions, our strategic partner, Vir Biotechnology, is conducting multiple phase II studies globally. When VIR-2218 or BRII-835, the siRNA was combined with VIR-3434 or BRII-877 and surface antigen specific and broadly neutralizing antibody. Greater reductions in surface antigen were achieved compared to siRNA alone. Initial data to evaluate BRII-835 and BRII-877 with or without pegylated interferon alpha are expected in the second half of this year. Additionally, off-treatment data from part A of this trial is expected in the first half of this year.
Vir is also presenting promising data last November from its ongoing phase II trial of 48-week combination of VIR-2218, 835, the siRNA, in combination with pegylated interferon alpha. At the end of treatment, nearly 31% of HBV patients receiving this siRNA and the pegylated interferon alpha combination achieved the surface antigen seroclearance with anti-surface antigen antibody seroconversion. Additional data will be available in the first half of this year. We are planning additional studies to expand our current findings and will leverage existing and emerging data to inform multiple phase II combination studies to be conducted by Brii Bio and Vir as we work in synergy to explore different combination regimens that could bring a high cure rate of functional cure for these patients with HBV.
A recent sharp increases in severe depression cases during the COVID pandemic and the lack of convenience and effective treatment options highlight the importance of our CNS efforts. We are developing BRII-296 and BRII-297, which are novel GABA-A receptor positive allosteric modulators, the PAMs. BRII-296 is a potential first of its kind long-acting one-time injection treatment for patients with PPD or MDD as first indications. With over 264 million people worldwide suffering from depression as reported by the WHO in 2020. We are also actively exploring potential other indications to expand. Pipeline results from our phase I study evaluating BRII-296 demonstrate the safety and feasibility of achieving a durable PK profile with a single administration in healthy subjects.
We have completed the phase I study and selected those for studies in patients, and plan to launch a phase II study to investigate the safety and the tolerability, as well as efficacy of BRII-296 in patient. In addition, we also will investigate the patient experiences and preferences for this one-time injection treatment. Following the Type C meeting with the US FDA, we are working closely with the agency to align and to fine-tune the design of this very important study. Early feedback from physicians and the patient communities has been very positive and reinforces the potential for this first-of-its-kind single injection treatment option for PPD and MDD patients. Moreover, we're advancing BRII-297, a new chemical entity developed internally as a long-acting injectable to address various anxiety and depressive disorders.
We're planning to initiate a first-in-human PK safety and tolerability study in Australia in the first half of this year. BRII-297, together with BRII-296, will provide us a full range of options to address many different anxiety and depressive disorders for our patients. As we look ahead, our sights are set high as we strive to be the pioneers in developing the first-of-its-kind treatment for PPD and MDD and for functional cure for HBV. For our HBV program, we believe that exploring novel combination therapies may lead to higher functional cure rates across all patient groups. Our innovative approaches are already showing promising results, and we're excited to continue working to bring these therapies to the market. For our CNS programs, BRII-296, we look forward to sharing more pipeline progress and additional indications in 2023 with you.
We're also making progress in tackling multiple drug and extensively drug-resistant MDR or XDR. Through the work with our partners, Qpex Biopharma in the U.S. Qpex, they have already accelerated the approval process for BRII-693, also known as QPX9003. BRII-672, also known as ORAvance, and BRII-636, also known as OMNIvance, are receiving Qualified Infectious Disease Product QIDP designation from the US FDA. Now Qpex completed first in human phase I studies with both BRII-693 and BRII-672, including a cohort of Asian subjects in each trial. Doses have been selected for respective studies in critically ill patients with gram-negative infections. BRII-693's highly differentiated safety and efficacy profile shows a great promise towards addressing the most difficult to treat carbapenem-resistant infections of Acinetobacter baumannii, as well as with Pseudomonas aeruginosa.
phase I studies, including an ethnic Chinese cohort, demonstrate the improved safety profile compared to the existing antibiotics in the polymyxin class. BRII-672 has the potential to become the first oral treatment in decades for complicated urinary tract infection, or cUTI. It has the potential to shorten or even avoid hospitalization, which we have fully recognized as a significant burden to our healthcare system, especially during the COVID pandemic period. phase I results support further development of BRII-672 in patients with a cUTI. In accordance with Qpex initial progress in the U.S., studies with BRII-672 and BRII-693 in China are underway now, with a pre-IND application for BRII-672 already submitted and a pre-IND for BRII-693 to be filed with an NMPA in the first half of this year.
For treatment-resistant Mycobacterium avium complex lung disease, our partner, AN2, is advancing a pivotal phase II/III trial evaluating BRII-658, also known as epetraborole, and reported positive results from its phase I bridging study evaluating the PK safety and tolerability of once-daily oral BRII-658. We plan to leverage the phase II data to progress clinical trials in China. All of our achievements in 2022 have positioned us for continued R&D growth across our programs, both in China and in the U.S., two of the largest healthcare markets in the world.
Our prioritized focus on HBV in China and on CNS in the US has allowed us to effectively allocate our resources and accelerate the progress of our programs, including enabling our U.S. R&D team to bring new CNS therapeutic candidates to humans and to expand indications. With that, I would like now to turn the call over to Dr. Ankang Li, our Chief Strategy and Financial Officer, to address the financials. Ankang, please. Thank you.
Thank you, Li, and thank you all for joining today's call. As a reminder, the financial figures I will be reviewing today are in RMB or Chinese yuan, unless otherwise noted. For the full year of 2022, our revenues were RMB 51.6 million from nil for 2021. The increase was mainly due to the commercialization of the long-acting amubarvimab, romlusevimab combination therapy in China for the treatment of COVID-19. Our other income was RMB 107.9 million for 2022, representing an increase of 9% compared with RMB 99 million in 2021. The increase was mainly due to the increased bank interest income of RMB 30.7 million, attributable to the increased bank and cash balance after the global offering. The increase was partially offset by the decrease in income recognized from PRC government grants.
Our total comprehensive expense for 2022 was RMB 238.5 million, representing a decrease of 94.4% compared with RMB 4,249.0 million for 2021. The decrease was primarily due to the decrease in fair value loss on financial liabilities at FVTPL. Our research and development expenses were RMB 440.6 million in 2022, representing a decrease of 10.9% compared with RMB 494.6 million in 2021. The decrease was primarily due to the decrease in third-party contracting costs relating to COVID-19 programs. It was partially offset by the increase in the employee cost for our continuous development in clinical trials. Selling and marketing expenses increased by RMB 26.9 million from nil for 2021. The increase was primarily due to the commercialization of COVID-19 therapy.
Administrative expenses for 2022 were RMB 168.6 million, representing a decrease of 19.1% compared with RMB 208.4 million for 2021. The decrease were primarily attributable to the decrease in employee costs. As of December 31st, 2022, our bank and cash balance, including restricted bank deposit and time deposit, was RMB 2,999.3 million, compared with RMB 3,355.1 million at end of 2021. The decrease was primarily due to payout of daily operations and third-party contracting costs. As we continue to advance our existing programs and expand our pipeline through both in-house discovery and external partnership, we expect our current funds to support our development needs through 2025.
We look forward to delivering continued shareholder value as we advance innovative therapies with the goal of broadening choice and access for patients. Going forward, we will continue to diversify our cash deposits in large commercial banks to support operations both in China and U.S. This concludes our prepared remarks. We will now open the call to your questions. Chris, please go ahead. Thank you.
Yeah. Thank you, Ankang. All participate, please kindly noted that we are open the line for Q&A. If you have questions, please click Raise Hand in the web and mail control panel, and operator will unmute you. Okay. The first question is from Dr. Chen Chen from UBS. Please, operator, unmute Chen Chen. Thank you.
Hi. Can you hear me?
Yeah. Dr. Chen, go ahead.
Okay, cool. Yeah, my first question is about HBV. In the phase I trial, like, two participants receiving the combo therapy showed promising results. I'm just wondering if there is any follow-up data like, of their hepatitis B, so if it's antigen, like for these two patients now. Yeah, because I'm curious. What is the trend like? Also some other company announced their PD-L1 data on HBV functional cure, and their data looks very exciting, although the patient number is still quite small.
How do you comment on the potential of PD-1, PD-L1 drugs for HBV functional cure? Yeah. Also I'm wondering, will you consider to introduce PD-1 drugs in your combo therapy? Yeah, this is about HBV. My second question is about HIV, I noticed that you have introduced a new candidate. This is subcutaneous injection. Can you share with us some more color on this molecule, such as what's its MOA? Thank you.
Well, thank you, Chen Chen. Great questions. I'm gonna ask Qing Zhu, our head of China R&D, to answer the question related to HBV. I would ask David Margolis, our head of Infectious Diseases TA, for the second question related to HIV. Qing, please.
Yes. Can you guys hear me?
Yep.
Okay. To the first of the question, the two participant was doing in the process of follow-up. The result will be disclosed late this year when it's available. Regarding the PD-1 result, yes, for the small number, right now the subject with very low baseline, if you look the data very carefully, you will see two out of three patient maintained as antigen loss during the follow-up. Their baseline level is quite low, less than 10 IU per ml. The PD-L1 has the different mechanism of action as the therapeutic vaccine.
Both immunomodulation was more towards the activate de novo immune response, whereas the PD-L1 to restore exhausted immune response. We do think the combination of the two could have, may have the additive effect. That's something that we are also can do the investigation, evaluate, see if there is the synergy down the road for the future development.
Can you please remind me what's the baseline in your combo therapy?
Our baseline is less than 3,000 IU per ml. The two participant, achieved as antigen loss, as a baseline, all greater than 700 IU per ml, which is quite, relatively higher than, most of the, reports right now for, response to the immunomodulation, which is usually less than 100 IU per ml.
I've got it. Thanks. Mm-hmm. HIV?
David?
Hi, this is David Margolis, Head of our Infectious Diseases Therapy Area. Thank you for the question around HIV. As you know, we have initiated another preclinical program looking at a long-acting agent for HIV. We expect that this drug will have subcutaneous, an opportunity to use a subcutaneous injection because of the potency and the volume that we anticipate. Although we still need to do additional animal work to make sure that we can validate that approach. As we stated in our public statement, we expect the potential that this could extend out from once monthly or beyond. In fact, we anticipate looking at injection out to potentially up to every 6 months.
As a treatment modality, it would need to be combined with another agent to form a combination regimen, although it has the potential as a preventative agent to be used as monotherapy. We haven't yet disclosed all of the mechanistic actions, so we can get back to you on that with more information, but it is an existing known mechanism of action within HIV. As I said, as a treatment modality, it would have to be combined with other agents.
Thank you, David. I just wanna add, Chen Chen, that you should also pay attention to another study that's conducted by Gilead looking at siRNA plus PD-1 and plus TR. You may be able to get some information from that study, you know, just to look at the potential which related to your question about PD-1 or PD-L1. Okay.
Okay. Thank you. Yeah. Also, can I ask another one? Like you terminated, for HIV drug, you terminated like BRII-778. Are you still, like, looking for a drug to combo with BRII-732?
Yes. I'm gonna defer that to David again to answer the question.
Yeah. BRII-732, again, we are continuing development, so we have a planned study to initiate a tablets evaluation with BRII-732 expected to begin 2Q. We're actively continuing development. It will need a combination regimen for treatment. We are in active discussions with partners about the potential to combine, have also considered potential internal programs along those lines. Remains to be seen the exact approach, but it will require a combination therapy.
Thank you, David.
Okay. Thank you, Dr. Hong and team.
Okay, thank you. The next question is from Jack at Morgan Stanley. Please go ahead, Jack.
Hi. Thank you, Chris. Can you hear me?
Yes.
Yes.
Hi. Thank you. I just have two quick questions regarding HBV pipeline. I think the management has shared that we'll expect to have more data update later this year. I just first question, just wondering then, in terms of how to view the upcoming data, what's the bar that the management will consider for the phase II trial to be sufficient to move on to reducing registrational study? I think other company has mentioned this 30% bar to, you know, move on on a regulatory basis. What's the management's thought in terms of what it would take to move on to the phase III stage?
Two is that just in case that the whatever the bar is, the phase II study result doesn't meet it, what's the likelihood that the company is able to use, Vir's data to initiate a registrational study in China, considering that there is some design and patient baseline dosing differences between their studies and our phase II studies?
Jack, that's a good question, so I'm gonna ask Qing to answer that first, and then I'll see if I have anything to add.
Hi, Jack, this is Qing. It's all very good questions right on the spot. In terms of the cure rate, usually for the target product profile in the field, people generally believe, greater than 25-30 will be sufficient to move to the registration. However, it's also dependent on the patient population and also what therapies that you compare to. We are actually also targeting that number before we can make a decision for any programs that move into the registrational studies. For our partners program, we are working very closely, so we are collaborating each other's clinical data and try to identify the optimal combination regimes, and then we can move together to the registrational study. There's a lot of collaboration and also the emerging data should come late this year and then 2024 to help us make that decision.
Yeah. Thank you, Qin. I think for the Vir data, you're exactly right. We're working together, and then we do study slightly differently, but this allow us to, you know, combine our dataset and to kind of test a broader range of regimens. With regard to data, and I think Vir is conducting most of their data in APACs, and many of the cohorts, their cohorts actually are from ethnic Chinese. I do think they're very helpful for the future registration in China. I think, you know, bottom line is, I think the bar will continue to be raised as we move forward. You know, we'll probably, as a starting point, 25%-30%, as Qin mentioned, is a good starting point. Obviously, as we continue to develop the curative regimen, we expect that number to go higher as we bring more product into the testing.
Got it. Thank you so much, Doctor. That's all the questions I have.
Thank you, Jack.
Yeah. Thank you, Jack and Zhi and Qin. The next question is from Yichen at CICC. Please go ahead.
Thanks. This is Yichen from CICC. Can you hear me?
Yeah.
Yeah. Congratulations you guys, you have achieved all goals this year. Could I ask two questions? The first one, you know, we are waiting for the results of treatment data of BRII-835 plus pegylated interferon alpha in the first half year this year. You know, just pay 10%, but what kind of data do you think is. I have a follow-up on PPD as well.
Okay. Let me ask Qing Zhu to answer the first questions regarding the, I think, the learning from the combination study of BRII-179. Go ahead, Qing Zhu.
Hi, hi, Nick. The learning consists of a couple of things. The first, the 3179 alone that, you know, we actually evaluated in the past, compared to this data, the combination results clearly show the stronger antibody response and immune T-cell response. This interim finding suggests that the combination does elicit a better response. Removal of the tolerogen by siRNA, treating in combination with a therapeutic vaccine, seems to have the additive effect in terms of reducing antigen-specific, HBV antigen-specific immune response. However, this also tells us, as we showed only two participants so far from the combination therapy achieved S antigen seroclearance.
The immune response is not sufficient enough in this combination regimen at this point, from the data we obtained. Clearly, we want to, kind of from this data, the insight we gain, and plus all the other emerging data from our partner and also competitors, just to look at the patient population and then those responders, hopefully guide us to, design the next, you know, better combination regime.
Thank you, Qing. I think this is also a very, very good question. I think we learned a lot through this study as well as the previous study we did with therapeutic vaccine alone. We were really surprised by the comparison of the therapeutic vaccine in HBV patient versus the vaccine that our partner, VBI, was doing in the non-infected patient population for the prophylactic vaccine. You can tell from that just how profoundly immune compared HBV patients are related to the immune responses to the surface antigen and pre-S1, pre-S2 as well. This clearly validate that the HBV patient, their immune response, the adaptive immune response are very much impaired and exhausted.
I think a lot of the time, when you look at this data, and then you look at who has the strong antibody response, who actually responded and who actually didn't respond, I think these are the very interesting scientific question that will inform the future design of the treatment regimens. These are the things that we're looking very carefully and then, and decide, you know, what additional study to be launched to investigate, you know, just based on the information that we're able to obtain from the study. What's your questions for PPD?
Perfect. Yeah, just on PPD, trying to get a sense, when do you expect to start, the phase II for 296 and PPD? How long do you think, it'll take to enroll and read out data? As far, you know, as much as you can say, could you give us, a sense of what the phase II trial design features could be, and maybe what you're hoping to see in terms of efficacy, and safety in that trial? Thank you.
Yeah. Thank you for the questions. I think, you know, over the past six months or longer, we have had very close interaction with FDA. Clearly FDA is very interested in this program. This is obviously a potential treatment disruptor. For this time that we've been talking more, it's actually not about the design of the study. It's not about the dose that we have selected. More of that is talk about the safety monitoring plan that we have in this particular patient population where, you know, you not only have to consider the safety of the mother and also the safety of the infant. I think this is something that we are talking to FDA and working with them closely on a treatment protocol.
As I mentioned early on, in the U.S., we are going through a 505(b)(2) pathway, so we have to really go through this PPD engagement. With the data that we're able to select the dose from the phase I study, we're also now designing the protocol for the MDD, which we believe is much bigger disease prevalences. We are doing both. I think, you know, the safety environment for the MDD is obviously very different because this does not involve a baby. I think this is, all of this is ongoing, that we're working with FDA through multiple meetings and interactions. Stay tuned for that. Hopefully, as soon as we align the our safety monitoring plan, we'll start a study, and we'll share the information with you.
That's great. That's great. Thank you for the updates. I just wanted to clarify, which dose are you moving forward into phase I for 296? Is it the same dose you looked at in phase I, or has your thought...
Yeah.
changed at all?
That's precisely correct. It's the phase I dose that we are choosing to the phase II.
Excellent. Thank you very much.
Thank you.
Okay. Thank you, Nick and Zhi. The next question is also from UBS, David. David, please go ahead. David?
Me?
David, can you say something? Yeah, we can hear you.
Okay, great. My question is about so I see that you have screened out a new candidate on the HIV BRII-753, and is also seeking for the potential partnership on the potential combo therapy. I see there are quite a lot of potential opportunities on the BD. I'm actually trying to ask if there's any colors on your BD opportunities this year. Also regarding the recent events of the SVB thing.
We are also quite interested in about the cash position, also about the ratio, how much cash is actually saved in China and how much is overseas, and also about the cash burning. Like, do you have any plans for about the expenses plan in the coming year and also the coming years? Thank you very much.
Thank you, David. I'm gonna ask our Chief Business Officer, Susannah Cantrell, to answer the question related to the HIV business partnership discussion as much as she can tell, and then I'm gonna ask Ankang to talk about the cash situation.
Thank you, Zhi. Thank you, David, for the question. This is Susanna Cantrell, the Chief Business Officer. Yes, we are seeking partnership, as David had noted, for the BRII-753 program that we're just moving forward. We are in active discussions. Our strategy is to look for a partnership that will accelerate the program and provide value for us as we grow and move the program forward. In terms of who we're in discussions with, we certainly can't disclose that. I don't know, maybe David might have some commentary on MOAs or specific things clinically that we're looking for.
You know, I think where we see the differentiation and the, and the potential value for BRII-753 is obviously a couple of things. The, the ability to administer as a sub-Q injection, the key differentiation there, as you may know, there are approved medications, long-acting medications in the HIV space that are intramuscular, either once every month or every other month. The key issue there is that the IM injection has to be administered by a healthcare authority or, you know, a healthcare facility.
These patients have to come in every month or every two months for a visit for that injection. The possibility of sub-Q is that could become a self-administered injection, freeing up the patients further, and just allowing them to come in when necessary for follow-up rather than to get their medication. What we're focused on with the partnership is to try to look for another sub-Q option if possible, so that the entire regimen could be administered both infrequently but also as a, as a sub-Q injection, potentially self-administered.
Thank you, David. Thank you, Susannah. Now the cash situation, Ankang.
Hi. We project to have a burn rate of around $100 million a year for the next two-three years. Currently, the projection for this year, 2023, will be a little lower than $100 million. I think our cash position is still over $300 million now, so we think we will be able to support the company through 2025, and by which time we hope that we will have good data from HBV and our CS programs that will allow us to raise more capital to support the further development of the program.
Ankang, what you're saying is that our cash position is actually more than $400 million, so we expect by the end of this year.
Yeah.
still in excess of $300 million.
That's right. That's right.
Right. Then regarding the cash split, you know, deposit rate due to the SVB situation, can you just tell people a little bit about how we diversify our cash?
Sure. First of all, SVB is now supported by Federal Reserve and the Treasury. All the deposits with SVB will be fully protected, so there won't be any loss for any depositors. In the wake of the instance of SVB, I think it's a kind of a crisis. We decided that we should further diversify our bank holdings. We are opening two accounts at two other large international banks. We will be having our cash deposit with at least three international banks, including, you know, some big banks in China, in Hong Kong, and in U.S. I think we will be protected.
Yeah. Just to be clear, right, our bank deposit in SVB is a small percentage compared our entire cash pile. We have this in SVB to support our payroll and our operation in US and paying contractor CROs. I think it's not a lot of money, but the point is for me is that we do not wanna be in the business of running on a bank. I think we continue to value our relationship with SVB. I think right now, everything is operating very nicely and we are, we're not being disrupted at all in terms of running our business. We are looking to diversify our cash as Ankang said.
Instead of being concentrating in one bank and we're gonna actually concentrate in multiple banks, and these are much bigger banks, so that will provide additional security to us. That's really I just wanna, you know, make additional comment on that. With HIV, just to say that It's interesting to see how the entire landscape is changing from, you know, daily oral drugs now to almost, you know, you look at Gilead and then, and GSK by Janssen and Merck, and they have all stated that going forward, long-acting will be their choices moving forward.
We think subcutaneous injection will be the best form of injections because they can be given self-administered. This is one area that we're very excited about it, obviously. As you mentioned that we need a partner. I think others also need a partner like ours as well. This is the area that we're determined to continue to create value through partnership. Thank you for the question.
Thank you. Thank you very much.
Yeah. Thank you, David question and Zhi and Ankang for the financial address. Almost Zhi has shared with us the ending remarks. Zhi, I will turn back the call to you to end the call.
Well, great. Well, thank you, everybody. It's great to have the opportunity to share our business with you again, I'm sure we're gonna continue to interact with each other as we progress this year in delivering our programs. I just wanna thank all of you for being so supportive of us and then interested in our progress, especially through the time of COVID. I know this is something that people have, you know, higher expectation. I can tell you as a company, we have done everything we can to move this program forward and then from discovery to approval in about two years. We've demonstrated our mission in terms of how to support China through the darkest time.
Remember 2021 when the Delta outbreak, that we are completely involved in, donating our program therapies to China. We feel very good about that and as a company, existing a society, and that's precisely what we need to do. As you can see, our focus on in HBV and CNS program, there are major public health issues, many of them have very challenging social stigma. All of these are not easy to tackle, we're trying to find a highly differentiated approach to do precisely that. I really appreciate all your patience, all your support and throughout the year.
I'm continue to look forward to work with you and having you support us to continue to progress our on the achieving HBV functional cure as well as having a very different treatment option for people with mental health disorders. With that, I wanna close this call and thank you and thank my management team for participating and thank our staff for supporting this call. Thank you very much. Have a very good day.
Yeah. Thank you, Zhi and everyone for joining. Goodbye. Let's end up the call.