Brii Biosciences Limited (2137) Earnings Call Transcript & Summary

Good day, ladies and gentlemen, and thank you for standing by, and welcome to Brii Biosciences Limited 2021 Annual Results and Business Update Conference Call. [Operator Instructions] It is now my pleasure to turn the call over to Ms. Chris Fang, Director of Investor Relations. Please go ahead, Chris.

Thank you, operator. Welcome to Brii Bio's 2021 Annual Results and Business Update Conference Call. Our annual results announcement can be found on the Investor Relations section of our company website. Joining today on the call from Brii Bio's senior management team are Dr. Zhi Hong, our Co-Founder, Chairman and Chief Executive Officer; Mr. Rogers Luo, our President and General Manager of Greater China; Dr. Li Yan, our Chief Medical Officer; and Dr. Ankang Li, our Chief Financial and Strategy Officer. Dr. Hong will provide a high-level overview of our key programs, company strategy and future development plans; followed by Mr. Luo, who will summarize further details about our HBV and COVID-19 programs and our overarching prioritizations of R&D and commercial efforts in China. Dr. Yan will provide updates on central neuroscience programs as a priority for the U.S. team. Dr. Li will then provide a brief summary of our full financial results and corporate strategy, including business development plan. After the management team's presentation, we will open the Q&A session to take questions. Before we start, we would like to remind you that for today's discussion may contain forward-looking statements, which involve a number of risks and uncertainties. Actual results and outcomes may differ materially from those mentioned in today's announcements and this discussion. The company does not undertake any obligation to update these forward-looking informations excepted as required by law. Now I'll turn the call over to Dr. Hong, our Co-Founder, Chairman and CEO. Dr. Hong, please go ahead.

Thank you, Chris. Thank you all for joining us, and welcome to our 2021 financial year results and the business update call. It has not been launched since our last call, we are very pleased to update you with our latest progresses. Less than 4 years ago, we launched the company with a mission to be the best public health inspired biotech tackling some of the world's greatest public health challenges with breakthrough innovation and insight. We have done just that. Almost all our programs aim to address huge disease burden and social stigma from diseases of HBV or HIV infection to mental illnesses. But these goals cannot be accomplished by 1 organizational alone. Partnership with investors, governments, societies are needed to truly deliver much needed support and innovation to those who need it. We made significant progress in 2021 to bring us closer to reaching these goals and look forward to further advancing our mission in 2022. Early in 2021, we completed a Series C financing, moved our HBV functional cure program into combination studies in the APAC countries or regions. Together with our partner, Vir Biotechnology, we are currently testing 4 different combination of HBV therapeutics. With the support of our investors and partners, the promise of transformational therapeutic options, we completed our IPO listing on the Hong Kong Stock Exchange in July 2021, raising nearly HKD 2.8 billion. As we continue to move our COVID-19 antibody combination therapy from the clinic to regulatory submission and the world have faced resurgence in COVID-19 with the Delta and Omicron variants, and regarding the critical and urgent need for safe, effective therapeutic options. As of December 2021, we are honored to be the first company in China to successfully develop and gain biologic license application or BLA approval from China's NMPA for the COVID-19 treatment. In less than 20 months, we're able to move amubarvimab and romlusevimab, which is the COVID-19 antibody combination therapy, successfully from the laboratory through clinical trial to gain the regulatory approval. Just last week, National Health Commission of China added our neutralizing monoclonal antibody combination towards COVID-19 Diagnosis and Treatment Guideline, the ninth edition, marking a critical breakthrough in COVID-19 therapeutic drugs in China. Our Emergency Use Authorization, EUA remains under active review by U.S. FDA and is pending on satisfactory completion of FDA's inspection of the manufacturing site at our contract development and manufacturing company, CDMO. Today, we are working closely with governments and local authorities and our shared goal of delivering our important COVID-19 therapy to patient need in China and around the world. The ongoing COVID-19 surges in Hong Kong, Shanghai and other cities throughout China reaffirm our belief that the combination of probably health tools such as the effective treatment, masking, border access control and broader access to vaccines will all be needed to end the pandemic. Apart from COVID-19, our overarching business strategy is set on our long-term goals to address increasingly prevalent infection disease and the same as diseases. First among this and perhaps most important for China is chronic hepatitis B or HBV infection, where we are the leader in the race to identify a functional cure. Searching for a cure of HBV will be the top priority of our China team, which has led the clinical investigation of our Phase II clinical stage assets in various combinations. Postpartum depression is another example of how we are leading the industry in searching for a truly transformational therapy for women who suffer from these terrible mental illnesses, who unfortunately at support our understanding of empathy from those around them. The current standard of care is simply inadequate, awareness of the disease is insufficient, further exacerbated by the gaps in our health care system and the lack of treatment options. Our U.S. team is leading the effort in launching our clinical trial in women who are either diagnosed with PPD or at high risk of developing PPD. 2022 will be an exciting year for our CNS programs with BRII-296, which is the single treatment option moving into the clinical trial in the U.S. for both treatment and prevention of postpartum depression. BRII-297, a new chemical entity will enter Phase I study in U.S., expanding our R&D effort in central nerve system diseases. I would also like to touch upon our endeavor for new HIV treatment, gave some background on the activities surrounding islatravir and also now as the FDA. First and foremost, while the U.S. FDA has put a hold on all trials related to islatravir or the FDA since December 2021, due to the observation of decline in CD4 cell count in some subjects. There were no safety concern nor any decrease in CD4 cell count in our Phase I study of BRII-732, which is the prodrug of islatravir, also known as the FDA. The clinical hold by U.S. FDA on BRII-732 was a decision made out of abundance of caution by both Brii and the agency. The last multiple rising dose cohort had not yet been dosed at the time and it is no longer needed, which means our Phase I study has completed. The data will be presented at a future scientific conference in the second half of 2022. And based on the published data and information disclosed by Merck, the safety finding of CD4 cell count decrease is both dose and time dependent. And we believe based on our Phase I study, we can define a select safe dose of BRII-732 and then that will be applications. As such, we will meet with FDA and discuss our plan to investigate and to further develop BRII-732 with the aim of lifting the clinical hold in the second half of 2022. We hope to proceed with the development of our once weekly oral combination of BRII-732 and BRII-778 as soon as we can. For our market log and extensively drug-resistant MDR/XDR gram-negative antibiotics, we are working in collaboration with our partners, Qpex, where we own the license rights for the development and the commercial activities in Greater China. Right now, Qpex is progressing BRII-636, BRII-672 and BRII-693 in parallel with the goal to moving all 3 assets to pivotal studies in the near future. I design Brii will consider participation in these trials by joining and conducting the Phase III studies in China, where there will be a critical need for this important hospital antibiotics. Leveraging the data from early U.S. studies and participating in late-stage trials in our licensing territory is part of our strategy to bring this critical medicines to market quickly without incurring significant early trial costs at risk. The last program I would like to highlight BRII-658, Epetraborole, which we licensed from AN2 Therapeutics for the treatment refractory non-tuberculous mycobacterial and also known as NTM infections. This is life-threatening lung diseases of affecting many patients in U.S., Japan and China. AN2 Therapeutics, which is based in the U.S., already filed for their S-1 prospectus and IPO registration in March 2022. BRII-658 is a novel -- completely novel antibiotics that has a potent and broad-spectrum activity against mycobacteria and many other bacterial pathogens. AN2 is developing Epetraborole as a once-daily RNA-administered treatment of patients with NTM with the initial focus on treatment refractory mycobacteria avium complex, also known as MAC, which is a very severe lung disease. AN2 is expected to initiate the registration Phase II/III study in the first half of this year, 2022. And the U.S. FDA has granted AN2 the orphan drug qualified infectious disease product and fast track designation for Epetraborole in treatment refractory NTM MAC lung disease. Our aforementioned achievements are also gaining traction in the capital markets with our addition to the eighth Asian indexes and the Hong Kong Connect exchange in the fourth quarter of 2021, which raises our visibility and added to our higher liquidity. We are also honored to have more than 10 awards from prestigious media and financial industry outlets that highlights our accomplishment in 2021. Being a very small and a young biotech, we are pleased to be recognized for our mission to tackle the world's greatest challenges in public health. In 2022, it's right to do more. With our forthcoming inaugural ESG report, we will highlight our convictions around our corporate social responsibilities and especially there is that further integrated our values across each aspect of our company while advancing public health at a global scale. Our momentum and success in 2021 have pushed us to the next stage in commercialization and manufacturing. This has significant implication in our longer-term business strategy and planning, which may accelerate our growth, expand our business opportunities. Our pipeline is very unique and strong, aim to change the way how patients are cared for. At the same time, eliminate social stigma rooted deeply in many communities facing public health in equities. Lastly, we see a remarkable opportunity to tap into patients' insights while creating our medicines. Following our patient-centric values, we are embarking a new investment into patient advocacy to establish relationship, share knowledge and ultimately guide us in our clinical development endeavors and to better serve our patients in need of innovative medicines. So with that, I would like to turn the call over to Mr. Luo and our President and General Manager of the Greater China, who will provide additional details on our ongoing focus in HBV clinical development as well as COVID-19 antibody commercialization in China. Rogers, please go ahead.

Okay. Thanks, Zhi. Hello, everyone. It's a great pleasure to speak with you today. And I would like to echo Dr. Hong's thanks for joining us on today's call. Our R&D pipeline holds great potential globally with our resource focused on tackling large disease prudence around the world. As many of you know, we have operations in both U.S. and China, and our programs are designed to strategically maximize how we assign disease indications, geographically. In China, our team is dedicated to finding a functional cure for HBV and introducing new cures for multidrug and extensively drug-resistant for an active infections and tuberculosis and non-tuberculosis mycobacterial infections to our ownership with Qpex and AN2. The reason we are developing these medicines here in China is simply because China is also the largest market for these disease indications. So as we bring our programs through clinical developments, we can enroll patients faster, the need is greater and if approved, we stand ready to have the largest patient populations in the world first. Taking a closer look at our China -- Chinese clinical operations and achievements in 2021, we are proud of what we have accomplished so far, particularly with our HBV assets. BRII-179 and BRII-835. More recently, in February of this year, we completed patient enrollment in our Phase II APAC study that combines BRII-835, which is also VIR-2218 and BRII-179 also called VBI-2601. Our strategy has always focused on emanating immunosuppressants and boosting sustained immunological control. We think both elements are needed to achieve the results we want, and we -- that study has been fully enrolled with 90 patients from New Zealand, Australia, Singapore, Hong Kong, Taiwan, South Korea and Thailand. We are on track to report top line interim data at the end of the year. With this combination therapy, we could provide the solutions to accomplishing our goal of using our functional cure. Our expectation is that the top line interim result will give us more guidance for how we will proceed. With positive data, we would like to consult with the Chinese Center for Drug Evaluation, CDE, after NMPA and submit investing additional new drug application to initiate the pivotal study in 2023. Meanwhile, we are also focusing on educating internal and external key stakeholders on our scientific topics, care pathways and patient outcomes. The team in China have engaged very well with external stakeholders about the value of our HBV functional cure and its impact on eliminating the social stigma of HBV infections. For BRII-835, we expect to announce the safety and antiviral activity fundings of the Phase II BRII-835 monotherapy study conducted in Mainland China in the coming weeks. This will be the first report that demonstrates an siRNA therapy treatment in the Mainland Chinese patient population. Our partner, Vir also is evaluating the combination of BRII-835 and HBV surface antigen neutralizing antibody VIR-3434 in a Phase II study. We are working very closely with Vir to mutually agree on their proof-of-concept criteria as we have the exclusive option to license VIR-3434 for development in Greater China. Should their proof-of-concept criteria be met, we will likely exercise the options in the second half of 2022 and bring VIR-3434 into our HBV clinical portfolio. Accelerates and combine our others HBV clinical candidates. For BRII-179, it has the potential to break immunotolerance to induce or restore B cell and T cell responses, providing a durable immuno response to HBV. In December last year, we began dosing non-chronic HBV subjects in the Phase II combination study where we are looking for the safety and efficacy of this novel recombinant holding therapeutic vaccine when it's added to the existing standard of care, which is the therapy of pegylated interferon alfa and NRTI. Right now, we expect to enroll approximately 120 patients for the first part of the study, which is Phase IIa in the second half of 2022 and expect the top line interim results will be available in the first half of 2023. Earlier in 2021, we successfully completed our Phase Ib/IIa study evaluating BRII-179 conjunction with VBI where we led the trials clinically designed and studied implementation in APAC. Shortly thereafter, our data were accepted and presented at the International Liver Congress in June at 2021. This promising human part of mechanism data reinforce the potential of BRII-179 to be a critical component in the development of a functional cure for chronic hepatitis B, which could have patients and health care providers manage their effects of this devastating disease and really curb the disease progression. On top of Brii's 2 ongoing trials according to our partner Vir's annual report on Form 10-K filed with the U.S. Securities Exchange Commission on February 28th this year, additional data from the Phase II trial of VIR-2218 or BRII-835 in combination with pegylated interferon alfa and the Phase II MARCH trial of VIR-2218 in combination with VIR-3434 may be presented at a scientific conference throughout this year. And some of the clinical trial sites are in Ukraine and Moldova. Vir is monitoring the situation determining any impact resulting from the current conflict in this region. Now we -- moving to the COVID-19 program. Both our China and U.S. teams work on our COVID-19 combination therapy, as it was important to develop our therapeutics with a global approach. As Dr. Hong just mentioned, in March this year, the National Health Commission of China added amubarvimab and romlusevimab combination to this COVID-19 diagnosis and treatment guidelines, the newest addition for the treatment of COVID-19. The progress was also part of the NIH-sponsored global Phase II/III study, allowing for our inclusion of diverse patient populations and broader coverage of variance, our ability to rapidly gain BLA in China and our pending EUA approval from the U.S. FDA, gave our teams the experience in executing a global study with high international standard. The experience and knowledge we gained from going through this process, both well for our future clinic studies and regulatory filings and we hope to replicate this process even more efficiently in the future. As a small company, that has been granted with its first BLA approval in less than 20 months. We are in the process of building our commercialization team in China to support the potential stockpiling and commercialization in the future. Meanwhile, we are leveraging our public and private networking with Tsinghua University and other stakeholders as well as our contract development and manufacturing companies and other manufacturing capabilities. We believe that our antibody therapy continues to be maintained neutralizing activity against the Omicron variant due to its high dose and exposure, which is predicted to remain sufficient, significant above their observed IC90. Our U.S. FDA application remains on review by the U.S. FDA and is depending on satisfactory completion of their FDA inspections of the manufacturing site and our CDMO. Even a unique nature and mechanism of EUA, we cannot predict when and what decisions U.S. FDA will make but a way of working closely with our CDMO to respond to every regulatory inquiries. We are in active discussions with various government regarding stockpiling and commercialization of our antibody therapy. So with that, I would like to turn the call over to Dr. Yan to review more details on our recent clinical trial efforts in U.S. Dr. Yan, please go ahead.

Thank you, Rogers. Hello, everyone, and thank you for joining our earnings call today. As Zhi and Rogers have already given many details on our efforts in infectious disease, I would like to turn your attention now to our CNS programs, especially detailing some of our efforts in addressing the unmet medical need for patients suffering from various depressive disorders. Since the onset of COVID-19 pandemic, globally, we have seen a sharp increase in the number of people burdened with depression. We are investigating BRII-296 and BRII-297, 2 novel psychiatric pharma therapeutics that could bring new treatment options for patients with postpartum depression, major depressive disorder as well as other depressive disorders. As a synthetic version of a naturally occurring neuroactive steroids, BRII-296 is developed internally at Brii, leveraging our long-acting medicine development platform. It is administrated as a single intramuscular injection compared to the current standard of care for PPD, which requires a 60-hour or 2.5-day continuous IV infusion in the hospital setting because of the severe side effects, including loss of consciousness associated with the current standard of care. So you can obviously see the advantage of patient convenience with BRII-296. As a single injection, BRII-296 also provides 100% patient adherence. Furthermore, BRII-296 allows mothers to receive their treatment without any disruption of breast feeding, therefore, maintaining the very important mother-infant bonding. During the past year, we have already completed more than 10 cohorts of investigation in our Phase I study in the U.S. for BRII-296. We're now in the final stage of optimizing our dose selection and anticipate the completion of our Phase I study in the second half of 2022. Accumulating Phase I data already confirmed the desirable and long-acting PK profile of BRII-296 and have established a satisfactory safety profile. We are planning to discuss this program with the U.S. FDA to initiate 2 studies in patients with severe postpartum depression, are in patients with high risk of directing postpartum depression, i.e., 2 clinical studies in PPD prevention and in PPD treatment settings, respectively. We believe that BRII-296 has the potential to transform the paradigm of postpartum depression treatment as well as more importantly, for our patients with high risk of PPD, so in PPD prevention. BRII-297 is a new chemical entity discovered internally. It is a GABAa 10 positive allosteric modulator of GABAa receptor. BRII-297 is being developed for treatment of various depressive disorders as well as potentially for neurological disorders. We've already held a pre-IND meeting with the FDA last year, and we've aligned the regulatory and clinical strategy to bring BRII-297 to the first time in human clinical trial and beyond. We plan to submit the IND application to the U.S. FDA in the second quarter of this year, and subsequently, initiated the Phase I investigation of BRII-297. So with that, I'm now going to turn the call over to Dr. Ankang Li, our Chief Financial and Chief Strategy Officer, to review our financial updates and the business development strategy. Dr. Li, please.

Thank you, Dr. Yan. As a reminder, the financial figures I will be reviewing today are in RMB unless otherwise noted. For 2021, our other income was RMB 99.0 million, representing an increase of 17% compared with RMB 84.6 million in 2020. The increase was due to additional income recognized from PRC government grants in fiscal '21 period. Our research and development expenses were RMB 494.6 million in 2021, representing a decrease of 43.5% compared with RMB 875.5 million (sic) [ RMB 875.8 million ] in 2020. This decrease was primarily due to a decrease in third-party contracting costs relating to COVID-19 programs. Administrative expenses for 2021 were RMB 208.4 million, representing an increase of 101.6% compared with RMB 103.4 million for 2020. The increase was primarily due to the increase in employee headcount. In total, our comprehensive expenses for 2021 was RMB 4.2 billion, representing an increase of 262.2% compared with RMB 1.2 billion for 2020. The increase was primarily attributable to the RMB 3.0 billion increases in fair value loss on financial liabilities through profit or loss for insured FVTPL associated with the fair value increase of our preferred shares. I want to note that this is a noncash item and purely accounting adjustments. We do not expect additional charges like this in 2022 and beyond because our preferred shares have been converted into common shares at our IPO. Excluding noncash charges and expenses and the listing expenses, our adjusted loss for the period improved to RMB 480.7 million versus RMB 888.7 million in 2020. As of December 31, 2021, our bank and cash balance, including restricted bank deposits and time deposits was RMB 3.3 billion compared with RMB 1.1 billion at the end of 2020. The increase was primarily attributable to the proceeds received from our Series C crossover financing and RMB 2.8 billion in proceeds from our IPO. At our executives interviews earlier, this year, we will focus on both advancing our existing programs and expanding our pipeline. Our pipeline growth will come from both in-house discovery and external partnerships, and we expect to add a number of new programs to our pipeline this year. Our licensing strategy is designed to expedite global regulatory approval, including accelerating our partner's global program in China and our in-house discovery program in international markets. This concludes our prepared remarks. We will now open the call to question-and-answer. Operator, please go ahead. Thank you.

Hello, operator, I think we can start with the Q&A session.

[Operator Instructions] The first question comes from the line of Sean Wu from Morgan Stanley.

Congratulations management for all the clinical progress and also of course, we are in antibodies now as part of that treatment regimen for Chinese government dealing with the COVID-19. So I have like the first question is about kind of for the new drugs in antibody. So what's your expectation? Like how much is the government with stockpile for this? And also, in the setting of prophylactic, like many patients, actually, 1 of my clients told me specifically, she's very worried about this. Her elderly grandmother, she may be like immune comprise that cannot take a vaccine, then how your new antibody may help out? So that's my first question. My second question is about your HBV functional cure. Clearly, this is very hot area and it's of very keen interest for a lot of people in China who have been previously infected with HBV. So what are the major readouts dates for people to see how you guys have made the progress in this regard?

Well, thank you, Sean, for the questions. Let me answer the HBV functional cure first, and I'm going to ask Rogers to answer your first question with the COVID-19 antibody commercialization effort as well as the potential prophylactic indication. Maybe I can chime in a little bit on the neutralizing activity against A2. So for the HBV functional cure, yes, we absolutely agree that this is something that is very, very important for patients, especially patients in China. So we are conducting, as we mentioned, 4 different combinations of therapeutic options, combinations with our partner, Vir. So the data will read out, our -- the data already read out with the combination of the siRNA and pegylated interferon. I think Vir will provide additional data hopefully at the EASL meeting in June. And then also, they are conducting another combination with the siRNA plus to neutralizing antibody. I think that data is also becoming available depending on the invasion in Ukraine, and you see what or not that's going to impact the data, the recruitment. And for us, we -- as we mentioned that our combination study, the siRNA plus therapeutic vaccine is fully enrolled. So it's just a matter of time for us to read out the data, which we project to be in the end of this year, we'll have the top line interim data, which is at the end of treatment. That should give us a good indication in terms what is the probability of success in achieving much higher functional cure rate compared to the current standard of care. Now the other combination of therapeutic vaccine plus pegylated interferon therapy in the partially responding patient population. That 1 has started getting enrolled and then we believe we can complete the enrollment in the second half of this year. And then we think the data -- the initial data will read out in the first half of 2023. So these are the programmatic milestones. And also, we mentioned that it's -- we have principally agreed with the POC criteria with Vir. And then we believe when they continue to deliver data to us and they're showing the efficacy and safety data of 3434, which is neutralizing antibody, we may exercise our option at the second half of this year. So these are in a way that it's almost a licensing milestones. These are the major milestone of catalysts in our mind in the next 12 to 18 months. Thank you. Rogers?

Yes. So like the first part of the question regarding the China commercialization. As you know, we have been actively engaging China central government, different agencies, things -- every things last year. So as you know that the current outbreak breaks in Shanghai and a lot of cities make us -- have been more actively engaged with [indiscernible] agencies. Since last week since the announcement of the new treatment COVID-19, we have been approached by more than 10 provinces and Chinese government asking for purchase of our antibodies. You can see there's a huge demand in the local level as there are already 28 provinces has new COVID-19 cases reported in recent months. So the need is there, and we have been very actively negotiating with them. And also, you can see from the reimbursement payer part on the China, the biggest payer is the Chinese government, the China Bureau for Reimbursement. They have published their kind of policy and encouraging local government to lease all the products in the new guidelines into the reimbursement list. As of now, we already told that some of the provinces already at least our antibodies into their reimbursement lease as [indiscernible] reimbursable. So I think in the later months -- weeks or months more provinces will count for in their reimbursement list, that's on the payer side. And so -- but talking about their antibodies role in whether [indiscernible] or treatment of compromise or suboptimal responders to the vaccines. As you know, that long-acting neutralizing antibodies is an important role to enhance their immuno protection for the people from COVID-19 infection with the other long-acting antibody has been approved for the prophylactic -- pre-exposure prophylactic and also post-exposure of prophylactic in other countries. Our antibody is also a long-anting antibodies. In summary, these antibodies can also enhance their immuno protection for the people. We are currently have 1 study actually in [indiscernible] national institutional respiratory disease. They are doing a small study evaluating our anybody in the cancer patients and see how the injection of -- infusion of antibody can prevent compared with not injected antibody compared with the neutralizing activity of the patients. So we are exploring the prophylactic indication in China. So as of now, I think this is -- we haven't got the indication as of now. So we are exploring now.

Thank you, Rogers. I just want to add that in a recent study conducted by investigator at the Singapore, we find our antibody combination therapy was very effective implementing the infection by the Omicron variant. So that gives us additional confidence that our antibody remain active against Omicron variant. Thank you, Sean, for the questions.

The next question comes from the line of [ Ron Luis ] from SVB Leerink.

So I have 2 questions on the COVID program. So regarding your EUA for your 196, 198 antibody regimen, are there any updates on the FDA's inspection of your manufacturing sites? And I think you mentioned you were working with your CDMO to respond to requests. Are these fairly straightforward? How quickly do you think you can work through those?

Yes. So -- thank you for the question. I think we -- obviously, FDA inspection unit had conducted the first -- the remote inspection. And so they have shared their inspection observations with our CDMO, and our CDMO have responded, and the FDA has also looked at the response and then engaging our CDMO directly and in addressing some of the increase and some of the resolution to some of the observations that they have. And unfortunately, in this case, we can really predict when FDA will take a decision on what decision they will make as we said in the corporate update. So we can't really comment any further other than the discussion is ongoing, the response and increase are ongoing between FDA and our CDMO.

That's fair. Interesting. And I was also curious for the antibody regimen, you mentioned it was recently added to the National Health Commission of China, COVID diagnosis and treatment guidelines. And I'm curious, what does that mean in terms of building physician awareness, education and interest in your June regimen?

Well, thank you very much, [ Ron ]. And I'm going to ask Rogers to comment on that.

Yes. Because the new treatment guide diagnosis and treatment guideline for COVID-19 was just announced last week, actually, we already have 3 real kind of online training programs has been -- have been done in China, and we are currently working with some of the educational agencies to plan for much broader education in China. That's from our side, but also from the Chinese National Health Commission, they also plan to arrange some activities -- education activities to educate the doctors, all of China, especially for those doctors working in the infection disease; hospitals which are treating COVID-19 patients, there were around 2,000 hospitals specifically designated to treat the COVID-19. So I think in later months, I would say, there will be many educational programs ongoing, either from the government side also from the medical community to educate and train their doctors and health care professionals with the newly released guideline.

Thank you, [ Ron ]. I think that answers your question. Sorry, go ahead.

It does. It's helpful. Last 1 for me. I was curious, you mentioned your PPD program and looking at prevention and wealth. How do you plan to identify patients proactively here for your therapeutic? And what -- are you going to use biomarkers or symptoms? Or how are you thinking about approaching that?

Great questions, [ Ron ]. I'm going to ask Dr. Yan to answer your questions. Li?

So for PPD prevention, what our current approach is to identify patients with high risk of developing PPD. So there are very detailed researchers in the past that in terms of identifying these high-risk patients, this including mothers, who had suffered from PPD from their previous childbirth. For example, if the mother is given a second child, and she suffered from PPD from her first delivery, this mother will have a high risk of PPD development in the second child birth. In addition to the previous PPD, mothers who suffer from other depressive orders and other psychiatric disorders, they also tend to have a higher risk of developing PPD. So if you take these risk factors together, it is estimated that it could have as high as 1 in 4 every 25% of the mothers that could suffer from PPD with high-risk factors. So that's our current approach. Of course, in conducting the trial, we will also take the opportunity to collect the samples and do some preliminary and biomarker researchers to identify if we could have a biochemical markers that will more precisely help us identify these patients in the future.

If I may add, [ Ron ], we're also looking to conducting some retrospective and prospective biomarker study through public/private partnership. As you know, there is no such a biomarker study in the past because there's no treatment option. So now we think there is a treatment option to prevent PPD. Therefore, the need for a biomarker study to understand the risk of women developing PPDs become much higher because this is the first program ever been looking into the prevention paradigm. I think there's a greater interest that we'll be able to bring together and then conducting such important biomarker research, which we do believe is something that deserve a lot of attention. So we're going to work with public funders and through public/private partnership and looking for this opportunity to investigate this biomarker study. Thank you for the questions.

The next question comes from the line of Wangbin Zhou from CICC.

This is Wangbin from CICC. So I have 2 questions. First is about our HBV portfolio. And now we have siRNA and preventive vaccine. And we also have the option to licensing neutralization for caused [indiscernible]. So since Vir has disclosed early normal priority data. So do I have any comments on this product and when we expect the licensing to this product? Is my first question.

Well, thank you, Wangbin, for the question. I think Wangbin, I think the line wasn't very clear, but I believe you're asking whether or not there's new data coming from the neutralizing antibody. I think Vir has disclosed early on pretty much on a cohort-by-cohort basis, look at the antiviral activity in the first 6-milligram and 18-milligram and 75-milligram. I think the patient dose higher to 300-milligram, I believe that's the top dose, they would go. I think we clearly identify a dose-dependent response, and which aided them to start designing our combination study, which they will be testing at the therapeutic doses, which is going to be at 75-milligram or higher, which we believe will be an important doses. Obviously, some of these data have not been published, so we can't really disclose that. And -- but we're looking forward to really look at the -- both the data from the monotherapy study as well and the combination study with siRNA at the therapeutic dose. And those are the data will be available to us soon, we hope. And then we can use that data and make a decision on whether or not we're going to exercise the option or not. I hope that answered your questions.

Okay. Got it. And the second question is for our HIV products. And we passed the clinical study in [indiscernible] due to the study test that occurred in the clinical trail is largely. So now do you -- can you show us more information about the side effect and when we expect our study to restart?

Sure. Sorry, I mean your line is really broken. I'm not sure I completely understand. Are you asking the question, what's our expectation in terms of when we're going to lift the clinical hold on the HIV program, the 732?

Yes, just when we can restart our projects, and can you give us more information about the studies that occurred in the clinical trial this last period.

Yes. So I'm going to try to answer your question, but your line is really broken. I'm not sure I completely got it. So forgive me if I didn't get the answer right. So here is what we know. I mean there's a lot we don't know, but there are some we know. So we know that there are daily regimens and weekly regimens in the monthly therapies that Merck were conducting. And this was a pretty massive number of studies. So we have seen a dose-dependent decline of CD4 cells. And in some of the cases, some of the doses was pretty significant and very profound and which is the reason that got FDA concerned. So we believe there are monthly does where they see significant CD4 cell discount. That 1 is being put on the full hold -- full clinical hold. And the weekly oral combination with a novel NNRTI, the MERCK-8507, that was also put on the full hold. In fact, if you look at the data, the NNRTI things also contribute to the decline of CD4 cell count. So we believe that regimen is going to have major issues because you have not only had to investigate this lateral where you also have to investigate the role of the NNRTI, which is going to be really, really complicated. The only regimen that FDA allowed them with a partial clinical hold is the daily therapies regimens at 0.75 milligram. In that cohort, they allow all the enrolled patients to continue to be dosed, which we believe is where the FDA is comfortable with the safety margin by that element. So -- and that's the kind of thing that we're looking at how we're going to be able to identify a safe dose from our Phase I study, which we believe we have identified a couple of doses that are within the safety margin that we believe FDA is considered to be safe. So therefore, this is something that we're going to propose to meet FDA soon and then discuss and as soon as we can to lift the clinical hold. So that we continue the study and move into the combination study with 778 as soon as we can. So I hope that answered your questions.

The next question comes from the line of [ Valerie Yu ] from Teng Yue Partners.

Hello, [indiscernible] can you hear me?

Yes, we can hear you.

Okay. So my first question is regarding any update on the China government procurement negotiation process on our neutralizing antibody since [indiscernible] already purchased by Chinese government with JPY 100 per case. So I don't know whether this is kind of like a price that we think will be reasonable for us.

Okay. Thank you, Valerie, for the question. I'm going to ask Rogers to respond. Rogers, please go ahead.

Yes. I didn't hear very clearly because line is just like not very clear. But if I understand it right, you are asking for the price of our antibody and also comparing with the prices of small molecules, if I understand it right. So for our case, in our case, we have not -- we have not finalized our pricing. So we cannot discuss it at this point. For the Pfizer small molecule, they already -- we heard that they already have a price in the market. But in our case, I think neutralizing anybody has a different role and value versus the small molecule as we just discussed in terms of the treatment window, or we can be -- our products can used for the patients within 10 days after the symptom onset and also about the drug-drug interaction. We know the small molecule has a lot of drug-drug interaction. And also about the liver and kidney function with the small molecule, they have some limitations. Furthermore, our antibody has enhance their immuno kind of protection for the patient for reinfection or you getting infected with COVID-19. So roles are not the attributes of their small molecules. So we have different role to play, and I think we provide different value over the small molecule. So regarding the price, as I just mentioned, we haven't finalized our price at this stage.

Yes. But how does -- what is our progress and update regarding the new negotiations with government procurement?

We haven't come to that stage, negotiate on the pricing, right? Because it's just been get into the reimbursement listing. As I just mentioned, the national, the biggest payer in China is the National Bureau for Medical Insurance. They just published their policy saying that they ask the local payer, which is the payer at the provincial level, ask them to lease other products recommended in the treatment guideline to be listed in their reimbursement list. They are not talking about negotiation on the price. I can provide an example here, which is the Jiangsu province, which is a very big province, has a large population at the coastal province. In their announcement, they already put our antibody into their reimbursement list. And it said they put the product at [indiscernible], which is fully reimbursed. And they are not mentioning about price. The government will pay for it because -- but in our case, we haven't finalized our price. But once we finalize our price, I think it can be fully reimbursed. So that's the situation.

So I think [indiscernible] but there is no impact involving on procurement schedules from the government, even though provisions of the government yet. So we don't know the [indiscernible] and we don't know the price.

Yes, as of now we just received -- as of now because we have already received, as I mentioned, many purchase requests from more than 10 provincial cities. They are not -- some of them mentioned about volume, I cannot tell here. Some of them didn't mention about the volume because they said, oh, we ask for a volume to purchase our product for stockpiling. Some of them ask for the treatment. So they -- some of them don't -- hasn't -- has not been asking for their volume. So we cannot -- at the current stage, we cannot predict their volume. Because another factor is that as the involving dynamic situation in China you now see -- you can see that today actually -- today announced their numbers of new cases is about 5,000 new cases reported. So it's also depending on how the pandemic will be evolving, right? That will largely impact the volume they need.

[indiscernible] we negotiated with the national reimbursement government. While in our case, we go into the provincial government, not the nationalist. Is there any reason there?

No. Usually, the mechanism is usually that, that national negotiations happened at the end of the year. We are now at the beginning of the year. I think COVID-19 is very different from the routine kind of update of the national reimbursement list. In our case, it's even more special because we haven't finalized our pricing. We -- our products are not currently commercially available at this stage. So usually, the product has -- if you're looking at the traditional kind of negotiation on price, the product has to be on the market, it has to be approved and negotiation always happens by the end of the year. For the Pfizer small molecule case, it's even very special. I think what I heard -- what we heard is that the French government has kind of negotiation with the company's headquarter, that's what we heard. We don't know, it's not confirmed. So it's a very special case. So I guess, because of newly released treatment guidelines, that there are only 2 products listed in this antiviral specific antiviral treatment. One is the small molecule and 1 is our product. So I think probably in the future, there will be some negotiation. But as of now, we already get some reimbursement in the provincial level listing. So it's quite special, quite different from the traditional mechanism, as of the emerging.

Yes, I have my last question here. Could you please update the manufacturing capacity target for 2020 -- 2022, sorry?

So for the manufacturing capacity, we are actively working with our CDMO to scale up the capacity but it's also depending on the commercial order and government supply, so -- and also the evolving of the pandemic. But I think if there is a need in the market, I think there will be a solution and capacity should be -- should not be a kind of a problem because if you're looking at how much inactive vaccines China produced is about 5 billion doses, right? I think that's of course, on the Chinese government fully support to support and control the pandemic in this very special cases. I think in that case, if there is huge demand, I think other stakeholders like government or others stakeholders as well, we're seeing, I think, will support to mid emergency -- emergent urging needs of the market.

Here one point, it was noting that we have around like 1 million case capacity in this year. So just wondering, considering the recent changing our CDMO supplier, will this number get decreased? Or as this year would be a new year so there's more capacity from them, so this number will be increased?

It's -- I would say, it's very depending on, as I just mentioned, it's very much depending on the commercial order and the government profile. I just can tell about that much.

The next question comes from the line of [ Edison Hong ] from Haitong International.

Sorry, due to the time, I think that's going to be the last question. Thank you. Please go ahead.

So I have 1 question for program 297. It's a very interesting challenging area in the past orders, I believe. And I want to know more about the result because there is -- I believe there's a larger program [indiscernible], which is short-term and off-label use in also capacity disorders targeting GABAa. So is that just a similar version to this off-label just? Or if it's different, in what way it's different?

Thank you for the question. I'm going to ask our CMO, Dr. Yan to answer this question.

Yes. As I mentioned, BRII-297 is a new chemical entity that we discovered internally. And it is a GABAa 10. So it's a different class of molecules. It acts on both intra and intra synoptics. So it has a different mechanism of actually as compared to the off-label as the patients want to use. And just to give you a little bit more details about this, we designed the drug so that it has a different PK profile. And we have put in some additional clinical features that could potentially make this drug more suitable for certain indications. So we have multiple indications that we could choose for this molecule developer, and this will be decided based on emerging Phase I data that we will see once we start the Phase I study.

Thank you for the question. And obviously, there are more than 10 different indications. So we think it's related to various depression disorder, movement disorder and other mental illnesses. So we believe having more product will help us to better cover the different indications. So -- and then obviously, with different clinical features and improved clinical features allows us to have a lot more flexibility to address all those indications. Now with that, I think I'd like to -- let's wrap up this call, and I want to thank you all for joining this call. I know we've bit of past the time. And as the CEO of the company, I truly appreciate you are really supporting us and paying attention to us and be interested in us. And as I said before, when we come to addressing big public health challenges, there's no 1 person alone, no 1 company alone, no 1 country alone or no 1 university alone can deal with this altogether. This obviously requires all of us working together, including investors investing in companies like us because we are going after major public health issue that making public safer in which we are residing. So I really appreciate this -- you genuine support. I know sometimes you feel that we have not gave you the full answer as much as we can. The reality is there's a lot of uncertainty with a lot of the, for example, the pandemics and how it's going to evolve. And I think we do actually appreciate the most recent change as we see very obviously in our discussion with the government, that there is a transition from 0 COVID into a more sophisticated integrated tools to address the pandemic, which we've been educating the government around the way and then pointing to that as the most important way to end the pandemic. And I think for us to end the pandemic, this is not going to be about how we control the pandemic through isolation and quarantine and diagnosis. And I think for us, truly end the pandemic, we need a variety of tools that we can address to help the society to get back to normal. So where there's a lot of uncertainty in our journey, you're investing hypothesis, but we do believe that by helping the company like us, we are doing a huge deal for the society. I hope at the end of the day, you work away with that part in your mind. We're not -- we should not be alone here dealing with this. The government must and should step up to help. And then obviously, there has come in a different part of their journey in terms of how they understand and address this ongoing pandemic. And so we hope in the near future, the policy will change. There will be more integrated approach to address this pandemic. With that, I want to thank you all for your time and your attention for us. And then thank you for your continued support to our company, which is truly a great company, at great biosciences. Thank you very much.

That does conclude our conference for today. Thank you for participating. You may all disconnect. Have a nice day.