Brii Biosciences Limited (2137) Earnings Call Transcript & Summary

[Audio Gap] Full Year 2022 Earnings Conference Call. Our full year results announcement can be found on the Investor Relations section of our company website. [Operator Instructions] Please be advised that today's conference call may be recorded. This is Chris Fang, Director of infector 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 then 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. [ Ching Zu ], Head of China R&D; and Dr. David Margolis, our Infectious Disease TA head. Before we start, I would like to remind you that today's conference may be -- contain 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 overview only as of the date of this recording and should not be -- 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 for joining our call today. It is great to be here and to share our progress in 2022. Our clinical programs have progressed significantly. We have refined key area of focuses, which will further drive our clinical programs in 2023, 2024. We have taken the liberty -- 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 progress across our pipeline of more than 10 differentiated compression diseases and central nerve system diseases. In terms of leadership, we have extended 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 readout from early to late-stage trials that demonstrate the potential of our therapeutic candidate to address a 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 affects 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 of post partum depression, or PPD, as well as major depressive disorder, or MDD, which we have -- which has significantly for new and innovative treatment options. And 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 -- activities outside of China. We are encouraged by the data generated today for BRII-835, a sRNA, and BRII-179, an 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. And together, these assets have the potential to be part of the functional acute 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 molecular antibodies against HBV. Each of our candidates has very unique therapeutic modality with a proven clinical mechanism of action, and which allows us to continue to explore different potential combination treatment in China for various patient groups. In the U.S., our primary aim is to develop BRII-296 for anxiety and depressive disorder with a specific focus on post partum depression and major depressive disorders. Our unique approach in this disease area to leverage patients' experience and the insight, which is the key differentiator in the significantly underserved disease category. Chronic antidepressive treatment are associated with a range of side effects or hence issue, stigma and concerns of not being able to get off treatment. Our goal is to offer a -- disruptors or paradigm shifting single treatment options that will enable patients to make easy decision to be on and off treatment. In our assets, to support molecular mental health, we are continuing to invest in patient and research and advocacy to address patients' needs 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 U.S. Food and Drug Administration, or FDA, to align and agree on a PPD treatment protocol in preparation for our Phase II proof of concept. 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 BRII-732 once-weekly oral therapy as well as BRII-753. The two compounds show great potential as key components in the long-acting HIV treatment regimen or as monotherapies or HIV prevention. Finally, in 2022, we commercially launched the amubarvimab/romlusevimab combination for the treatment of COVID-19 in China, which has been well received by physicians. Although COVID-19 is not a focus for us anymore, this experience is very valuable to ourselves, to our team and has proven our ability to quickly bring innovative drug to market. As a result of the constantly evolving COVID-19 trends, including the upcoming aspiration of the COVID-19 emergency authorization by the U.S. Department of Health and Human Services in May 2023, as well as contracted regulatory inspections at our CDMO sites, we have made a decision to discontinue the COVID antibody combination program and has stopped manufacturing [ effort ]. We are working with U.S. 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, whilst all the necessary regulatory requirements have been complete. We gained valuable insight working with the Chinese and the U.S. 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 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 single 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 broad pipeline of therapeutic candidates, focusing on infectious and CNS diseases. We're leading clinical developments with potential first-of-its-kind treatment of PPD and for MDD in the U.S. and a 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 sRNA to neutralizing antibody against surface antigen and to therapeutic vaccines to spur HBV-specific antibody and T-cell responses. The extensive pipeline gives us a strong competitive advantage and 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 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 sRNA. Last month, we presented the interim findings of this trial at Asia Pacific Association for the Study of Liver. The second trial is also a Phase II study, evaluating BRII-179 plus pegyl interferon. We have completed 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 El Paso last month demonstrated that BRII-835 and BRII-179, this combination was safe and well tolerated and was able to induce stronger antibody responses against the hepatitis B surface antigen. And also, this combination led to improved HBS surface energy specific T-cell responses when compared with either BRII-835 or with BRII-179 alone. All cohorts of patients achieved the HB surface antigen reduction at the end of the treatment with a mean decrease of 1.7 to 1.8 log international unit [ permit ]. In addition, two participants in the combination cohorts achieved maximum reductions in surface antigen at or below the lower limit of quantification by week 40, along with robust surface energy-specific antibody and T-cell responses. We expect to report additional data from this trial in the second half of the year, when we complete the follow-up of all participants. While we conducted studies in APAC countries and regions, our strategic partner, Vir Biotechnology, is conducting multiple Phase II studies globally. VIR-2218 or BRII-835, the sRNA, 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 sRNA alone. Initial data to evaluate the BRII-835 and 877 with or without pegyl 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 or 835 sRNA, in combination with pegyl interferon alpha. At the end of treatment, nearly 31%, 31% of HB patients receiving this sRNA and pegyl alpha combination, achieved the surface antigen sero clearance with anti-surface antigen antibody sero conversion. Additional data will be available in the first half of this year. We are planning additional studies to expand our current findings, and we'll leverage existing and emerging data to inform multiple Phase II combination studies to be conducted by Brii and Vir as we work [indiscernible] to explore different combination regimens that could bring a high cure rate of functional cure for these patients with HBV. The reason to sharp increases in severe depression cases during the COVID pandemic and the lack of convenience and effective treatment options highlights the importance of our C&S efforts. We are developing BRII-296 and BRII-297, with a novel CAPA receptor-positive allosteric modulators. BRII-296 is a potential first-of-its-kind long-acting onetime 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. Top line 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 select the dose for studies in patients and are planning to launch a Phase II study to investigate the safety and the tolerability as well as efficacy of BRII-296 in patient -- in [ combination ], we also will investigate the patient experiences and the preferences for this onetime injection treatment. Following the Type C meeting with the U.S. 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 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 SAD 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 of 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. And our innovative approaches are already showing promising results. And we're excited to continue working to bring these therapies to the market. As for our CNS programs, BRII-296, we look forward to sharing both our pipeline progress and additional indications in 2023 with you. We're also making progress in tackling multiple drug and extensively drug resistance NDR or XDR through the work with our partners, Qpex Biopharma in the U.S. Qpex, they have already exacerbated the approval process of BRII-693 also known as QPX-9003. BRII-672, also known as ORAvance, and BRII-636 also known as OMNIvance. By receiving qualified infection disease product QDP designation from the U.S. FDA. So Qpex completed the first-in-human Phase I studies with both BRII-693 and BRII-672, including a cohort of Asian paid subjects in each trial. Doses have been selected but respective studies in critical ill patients with Gram-negative Infection . BRII-693 is a highly differentiated safety and efficacy profile shows great promise towards addressing the most difficult-to-treat infections of a Acinetobacter baumannii as well as nwith Pseudomonas aeruginosa. Phase I studies, including an ethnic Chinese cohort demonstrated improved safety profile compared to the existing antibiotics in the class. BRII-672 has the potential to become the first oral treatment in decades for complicated urinary tract infection of cUTI. It has the potential to shorten or even avoid hospitalization, which we have fully recognized as a significant burden to our health care system, especially during the COVID pandemic period. Phase I results support further developments of BRII-672 in patients with the cUTI. In accordance with the 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 the an [ NPA ] in the first half of this year soon. For treatment-resistant mycobacteria avium complex lung disease, our partner AN2, is advancing a pivotal Phase II/III trial, evaluating BRII-658, also known as epetrabrole and reported positive results from its Phase I reading study evaluating the PK safety and the tolerability of once daily oral BRII-658. We plan to leverage the Phase II data to progress the clinical trials in China. All of our achievements in 2022 have preceded us, but continued R&D growth across our programs both in China and in the U.S., two of the largest health care markets in the world. Our prioritized focus on HBV in China and on CNS in the U.S. 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 CNY 51.6 million from NEO 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 were CNY 107.9 million for 2022, representing an increase of 9% compared with CNY 99 million in 2021. The increase was mainly due to the increased banking interest income of CNY 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 CNY 238.5 million, representing a decrease of 94.4% compared with CNY 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 CNY 440.6 million in 2022, representing a decrease of 10.9% compared with CNY 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 CNY 26.9 million from NEO for 2021. The increase was primarily due to the commercialization of COVID-19 therapy. Administrative expenses for 2022 were CNY 168.6 million, representing a decrease of 19.1% compared with CNY 208.4 million for 2021. The decrease was primarily attributable to the decrease in employee costs. As of December 31, 2022, our bank and cash balance, including restricted bank deposits and time deposits was CNY 2,999.3 million compared with CNY 3,355.1 million at the 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 to patients. Going forward, we will continue to diversify our cash deposits in large commercial banks to support operations, both in China and the U.S. This concludes our prepared remarks. We will now open the call to your questions. Chris, please go ahead. Thank you.

Yes. Thank you, Ankang. All participate, please kindly note that we open the line for Q&A. [Operator Instructions]. Okay. The first question is from Dr. Chen Chen from UBS.

Can you hear me?

Yes, Dr. Chen, go ahead.

Okay. Cool. Yes. My first question is about HBV. So in the Phase II trial, the two participants receiving the combo therapy showed promising results. So I'm just wondering if there is any follow-up data, like of their hepatitis B surface antigen but for these two patients now? Yes, because I'm curious. So what is the trend like? And also some other companies announced their PD-L1 data on HBV functional cure. And their data looks very exciting, although the patient number is still quite small. So how do you comment on the potential of PD-1 -- PD-L1 drugs for HBV functional cure? Yes. And also, I'm wondering, will you consider to introduce PD-1 drugs in your combo therapy? Yes, this is about HBV. And my second question is about HIV. I note that you have introduced a new candidate. So this is subcutaneous injection. So can you share with us some more color on this molecule, such as what is MOA?

Great questions. I'm going to ask [ Chengdu ], our Head of China R&D to answer the question related to HBV. And then I would ask David Margolis, our Head of Infectious -- for the second question related to HIV. Ching, please.

Yes. Can you guys hear me?

Yes.

Okay. So to the first of the question, the two participants were still in the process of follow-up. So the results will be disclosed late this year once available. Regarding the PD-1 result, yes, for the small number, right now, the subject with a very low baseline. If you look the data very carefully, you will see 2 out of 3 patients maintained as antigen loss during the follow-up. Their baseline level is quite low, less than 10 IU per ml. So the PD-L1 has the different magnum 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. So we do think the combination of the two could have -- may have the additive effect. So this is something that we also can do, the investigation, evaluate, see if there is synergy down the hill for the future development.

And can you please remind me what's the baseline in your combo therapy?

So our baseline is less than 3,000 IU per ml. So the two participants achieved as antigen loss as a baseline of greater than 700 IU per ml, which is quite relatively higher than most of reports right now for response to the immunomodulation, which is all less than 100 IU per ml.

Okay. And HIV?

David?

Yes. This is David Margolis, Head of our Infectious Disease Therapy Area. Thank you for the question around HIV. As you know, we have initiated another preclinical program looking at long-acting agent for HIV. And 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. And 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 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. And as I said, as a treatment modality, it would have to be combined with other agents.

And I just want to add, Chen Chen, you should also pay attention to another study that's conducted by [ Bilia ] looking at sRNA and plus PD-1 and plus TRR. And then you may be able to get some information from that study. Just look at the potential with related to your question about PD-1 or PD-L1.

Okay. Yes, and also can I ask another one. So like you terminated -- for HIV drug you terminated 778. So are you still, like looking for a drug to combo with 732?

Yes. I'm going to defer that to David again to answer the question.

Yes. So 732, again, we are continuing development. So we have a planned study to initiate a tablet evaluation with 732 expected to begin second quarter. So we're actively continuing development. It will need a combination regimen for treatment. And we are in active discussions with partners about the potential to combine have also considered potential internal programs along those lines. So remains to be seen the exact approach, but it will require a combination therapy.

Okay. So the next question is from [ Jack ] at Morgan Stanley.

Thank you, Chris. Can you hear me?

Yes.

I just have two quick questions regarding HBV pipeline. So I think the management has shared that we would expect to have more data update later this year. So 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 registrational study? So I think other company has mentioned the 30% bar to move on a regulatory basis, but what's the management thought in terms of what it would take to move on to a Phase III stage? And two is that just in case that 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 VIR studies and our Phase II studies?

Yes, that's a good question. I'm going to ask Ching to answer that first, and then I'll see if I have anything to add.

Jack, this is [ Li Ching ]. All very good questions, right? So in terms of the cure rate. Cure rate for the target product profile in the field, people generally believe greater than 25 to 30 will be sufficient to go to the registration. However, it's also dependent on the patient population and also what therapies that you compare to. So we are actually also targeting that number before we can make a decision for any programs and move into the registrational studies. For our partners program, we are working very closely. So we are elaborating each other's clinical data and try to identify the optimal combination regimes and then we can move together to the registrational study. So there's a lot of collaboration. And also the emerging data should come late this year and 2024 to help us make that decision.

Yes. Thank you, Ching. I think for the Vir data, you're exactly right, we're working together. And we do study slightly differently, but this allows us to combine our data set into kind of test -- a broader range of regimens. With regard to data, and I think Vir is conducting most of their data in APAC. Many of the cohorts -- their cohorts actually are from ethnic Chinese. So I do think they're very helpful for the future registration in China. I think bottom line is I think the bar will continue to be raised as we move forward. We'll probably -- as a starting point, 25% to 30%, as Ching mentioned is a good starting point. Obviously, as we continue to develop the regimen, we expect that number to go higher as we bring more product into the testing.

So the next question is from [ Li Jung at CICC ].

This is Li Jung from CICC, can you hear me?

Yes.

Yes. Congratulations. You achieved your goals this year. Could I ask two questions? The first one, just we are waiting for the results of treatment data of BRII-835 plus pegyl interferon alfa in the first half year this year. Just 10%, but what kind of data do you think -- maybe 10% or 20% over here? The second one is about the similar. If you plan to divide the clinical trial, by BRII-835 plus pegyl interferon into in China, how could you get to the usage of pegyl interferon alfa in China? Will you cooperate with other companies, produce pegyl interferon alfa? Yes. That's two questions.

Okay. I think the question regarding the follow-up for the sRNA plus pegyl interferon, I think the data has continued to mature and Vir has the plan to report in the first half of the year. I assume that's going to be [ easy ], I believe, in June. So just be patient and when those data are mature and they will be reported. And at this point, I cannot really give you any guidance in terms of what's the durability of the end of treatment response, which regarding the sourcing of pegyl interferon, there is a domestic manufacturer of pegyl interferon. There's also Roche's PEGASUS and there's also a couple of others, i.e., in Phase III NDA stage. So I believe that there are options with regard to pegyl interferon. So we are evaluating those opportunities and decide whether or not we should do something exclusively on not exclusively. Those are part of the thing that we are evaluating at the time.

And then the next question is Nik from SVB.

Can you hear me?

Yes.

Great. This is Nick Gasic on for Roanna Ruiz. Maybe first, I'll start with HBV. Trying to get a sense of some of the key learnings from the Phase II combination data set for 179 and 835 so far. Maybe which types of patients showed the greatest benefits in terms of s-antigen suppression and loss? And maybe what you're hoping to see in the full or additional data, which is expected later this year? And then I have a follow-up on PPD as well.

Okay. Let me ask Ching to answer the first questions regarding the -- I think the learning from the combination study of 835, 179. Go ahead, Li Cheng.

So learning consistent with a couple of things. First, the BRII-179 alone that we actually evaluated in the past, compared to this data, the combination results clearly showed a stronger antibody response and immune T-cell response. So this interim finding suggests that the combination does elicited better response. So removal of the -- tolerated by sRNA, treating in combination with therapeutic vaccine since they have the additive effect in terms of reducing antigen-specific -- HBV antigen-specific immune response. However, this also tells us as we show there are only two participants so far from the combination therapy achieved as antigen sero clearance. So the immune response is not sufficient enough in this combination regime at this point from the data we obtained. So clearly, we want to -- from this data, the insight we gained and plus, all the other emerging data from our partner and also competitors to look at the patient population and then those responders, hopefully, guide us to design the next data combination regime.

Thank you, Ching. I think this is also a very, very good question. And I think we learned a lot from the study as well as the previous study we did with therapeutic vaccine alone. And we were really surprised by the comparison of the therapeutic vaccine in HBV patients versus the vaccine that our partner VBI was doing in the non-infected patient population for the prophylactic vaccine. And you can tell from that, just how profoundly immune compare HBV patients are related to the immune responses to the surface antigen and Pre-S1, Pre-S2 as well. So we -- this clearly validate that the HBV patients that their immune response -- the adaptive immune response are very much impaired and exhausted. I think a lot of 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 responded, I think these are the very interesting set of question that will inform the future design of the treatment regimen. So these are the things that we're looking very carefully and decide what additional study to be launched, to be investigate just based on the information that we're able to obtain from the study. And what's your question for PPD?

Perfect. Yes. Just on PPD, trying to get a sense, when do you expect to start the Phase II for 296 in PPD? How long do you think it will take to enroll and readout data? And then as far -- 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?

Yes. Thank you for the questions. I think over the past 6 month or longer, and then we have a very close interaction with the FDA. And then clearly, FDA is very interested in this program, this is obviously a potential treatment disruptor. So 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. And more of that is talk about the safety monitoring plan that we have in this particular patient population where you not only have to consider the safety of the mother and also the safety of the infant. So I think this is something that we are talking to FDA and working with them closely on a treatment protocol. And as I mentioned earlier on, in U.S., we are going through a 505(b)(2) pathway. So we have to really go through this PPD engagement. But 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. So we are doing both. And I think the safety environment for the MDD is obviously very different because it does not have -- this does not involve a [indiscernible]. So I think this is -- all of this is ongoing that we're working with FDA through multiple meetings and interactions. So stay tuned for that. And hopefully, as soon as we align that -- our safety monitoring plan, we'll start the study and we share the information with you.

That's great. That's great. So I just wanted to clarify which dose are you moving forward into Phase II for 296? Is it the same dose you looked at Phase I? Or as you thought...

That's precisely correct. It's the Phase I dose that we are tuning to the Phase II.

So the next question is also from UBS, David.

Can hear me?

Yes, we can hear you.

Okay. Great. So my question is about -- so I see that you have screened out a new candidate on the HIV BRII-753 and it's also seeking for the potential partnership on the combo -- on the potential combo therapy. So I'm seeking -- so I see there are quite a lot of potential opportunities on PPD. So I'm actually trying to ask if there's any colors on your PPD opportunities this year? And also regarding the recent event of the SVB thing. And 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, David. I'm going to 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 going to ask Ankang to talk about the cash situation.

Thank you, Zhi. And thank you, David, for the question. This is Susannah Cantrell, the Chief Business Officer. Yes, we are seeking partnership, as David had noted for the 753 program that we've 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. But I don't know maybe David might have some commentary on MOAs or specific things, clinically, that we're looking for.

Yes. So I think where we see the differentiation and the potential value for 753 is obviously a couple of things. So the ability to administer as a subcu 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. But the key issue there is that the IM injection has to be administered by a health care authority, a health care facility. So these patients have to come in every month or every 2 months for a visit for that injection. And the possibility of subcu 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. So what we're focused on with the partnership is to try to look for another subcu option, if possible, so that the entire regimen could be administered both infrequently, but also as a subcu injection potentially self-administered.

Thank you, David. Thank you, Susannah. And now the cash situation, Ankang?

So we project to have a burn rate of around CNY 100 million a year for the next 2 to 3 years. And currently, the projection for this year, 2023, will be a little lower than CNY 100 million. I think we -- our cash position is still over CNY 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 CNS programs that will allow us to raise more capital to support the further development of the program.

So Ankang, what you're saying is that our cash position is actually more than CNY 400 million. So we expect by the end of this year still in excess of CNY 300 million.

That's right. That's right.

And then regarding the cash split deposit rate due to the SVB situation, can you just tell people a little bit about how we diversify our cash?

Sure. So first of all, SVB is now supported by Federal Reserve and the treasury and other deposits with SVB will be fully protected. So there won't be any loss for any depositors. And so in the -- we hope the incidence of SVB, I think it's a kind of a crisis. We decided that we should further diversify our bank holdings. So we are opening two accounts at two other large international banks. So we will be having our cash deposit with international banks, including some big banks in China, in Hong Kong and in the U.S. So I think we will be protected.

Yes. So just to be clear, right, the -- our bank deposit in SVB is a small percentage compared to our entire cash. And we have this in SVB to support our payroll and our operation in U.S. and paying contractors, CROs. So I think it's not a lot of money, but the point is for me is that we do not want to be in the business 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. But we are looking to diversify our cash as Ankang said. So instead of being concentrating in one bank, and we're going to actually concentrate in multiple banks, and these are much bigger banks, so that will provide additional security to us. So that's -- really, I just want to make additional comment on that. Now with HIV. Just to say that we're -- it's interesting to say how the entire landscape is changing from daily oral drug now to almost -- you look at [indiscernible] and [ Janssen ] and Merck, they have all stated that going forward, long-acting will be their choices moving forward. Obviously, we think subcutaneous injection will be the best form of injections because they can be given self-administered. So this is one area that we're very excited about it. Obviously, as you mentioned, that we need a partner, and I think others also need a partner like ours as well. So this is the area that we're determined to continue to create value through partnership. So thank you for the question.

So almost Zhi has shared with us the ending remarks. So 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, and I'm sure we're going to continue to interact with each other as we progress this year and delivering our programs. I just want to thank all of you for being so supportive of us and interest in our progress. And especially through the time of COVID. I know this is something that people have higher expectation. But 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 2 years, and we've demonstrated our mission in terms of how to support China through the darkest time in -- remember, 2021 when the Delta outbreak we are completely involved in donating our program therapies to China. So we feel very good about that. And as a company, existing society and that's precisely what we need to do. So as you can see, our focus on -- in HBV and CNS program, and there are major public health issues, and many of them have very challenging social stigma. All of these are not easy to tackle, but 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, and I continue to look forward to work with you and having you support us to continue to progress our -- on achieving the functional cure as well as having a very different treatment option for people with mental health disorders. So with that, I want to close this call and thank you and thank my management team for participating and thank our staff for supporting this call. So thank you very much. Have a very good day.

Yes. Thank you, Zhi and everyone, for joining. Goodbye. Let's end up the call.