Brii Bioscience Ltd

Good day, ladies and gentlemen, and thank you for standing by. And welcome to BRIE Biosciences Limited 2021 Annual Results and Business Update Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. 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 GreenBowl's 2021 Annual Results and Business Update Conference Call. Our annual results announcements can be found on the Investor Relations section of our company website. Joining me today on the call from GreenBowl's senior management team are Dr. Z. Hong, our co-founder, chairman, and the chief executive officer, Mr. Rogers Luo, our president and general manager of Greater China, Dr. Lee Yin, our chief medical officer, and Dr. Ang Kong Lee, our chief financial and strategy officer. Dr. Hong will provide a high-level overview of our key programs, company strategy, and future development plan, followed by Mr. Law, who will summarize further details about our HPV 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 UIC. 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 announcement and this discussion. The company does not undertake any obligation to update this forward-looking information accepted as required by law. Now I 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 long since our last call. We are very pleased to update you with our latest progress. Less than four 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 stigma from diseases of HIV or HIV infection to mental illnesses. But these goals cannot be accomplished by one organization alone. Partnership with investors, governments, and 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 HPV functional acute program into combination studies in the APEX countries or region. Together with our partner, Viewer Biotechnology, we are currently testing four different combination of HPV therapeutics with the support of our investors and partners and the promise of transformational therapeutic options, we completed our IPO listing on the Hong Kong Stock Exchange in July 2021, raising nearly 2.8 billion Hong Kong dollars. As we continue to move our COVID-19 antibody combination therapy from the clinic to regulatory submission, and the world has faced resurgence in COVID-19 with the Delta and Omicron variants, and revealing the critical and urgent need for safe and 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 of BLA approval from China's NNPA. followed the COVID-19 treatment. In less than 20 months, we were able to move amibarumab, aromalusivumab, 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 molecule antibody combination to AIDS COVID-19 Diagnosis and Treatment Guidelines, the ninth edition, marking a critical breakthrough in COVID-19 therapeutic drugs in China. Our Emergency Use Authorization, EUA, remains under active review by US FDA and is pending on satisfactory completion of FDA's inspection of the manufacturing site at our contract environment manufacturing company CDMO. Today we're working closely with governments and local authorities and our shared goal of delivering our important COVID-19 therapy to patients in 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 public health tools such as 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 infectious disease and the same as diseases. First among this, and perhaps most important for China, is chronic hepatitis B, or HPV infection, where we are the leader in the race to identify a functional cure. Searching for a cure of HPV will be the top priority of our China team, which has led to clinical investigation of our phase two clinical stage asset in various combination. Postpartum depression is another example how we are leading the industry in searching for a truly transformational therapy for women who suffer from these terrible mental illness, who unfortunately lack support or understanding or 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 healthcare system and the lack of treatment options. Our US 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 RAID 296, which is the single treatment option moving to the clinical trial in the U.S. for both treatment and prevention of postpartum depression. GRADE 297, a new chemical entity, will enter phase one study in the 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 islazovir, also known as EFDA. First and foremost, While the FDA, U.S. FDA, has put a hold on all trials related to isletrovir or EFDA since December 2021, due to the observation of decline in CD4 cell count in some subject, there were no safety concerns, nor any decrease in CD4 cell count in our phase one study of 3732. which is the pro-drug office, or also known as the FDA. The clinical hold by US FDA on Brie 732 was a decision made out of abundance of caution by both Brie 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 one 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 one study, we can define or select a safe dose of ray 732. And then that will be efficacious. As such, we will meet with FDA and discuss our plan to investigate and to further develop Brie732 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 Brie732 and Brie778 as soon as we can. For our multi-drug and extensively drug-resistant MDR, XDR, gram-negative antibiotics. We are working in collaboration with our partners, QPACS, where we own the license right for the development and the commercial activities in Greater China. Right now, QPACS is progressing Brie 636, Brie 672, and Brie 693 in parallel with the goal to moving all three assets to pivotal studies in the near future. By design, BRII will consider participation in these trials by joining and conducting the phase three studies in China, where there will be a critical need for this important hospital antibiotics. Leveraging the data from early US studies and participating in late stage trials in our licensing territory is part of our strategy to bring these critical medicines to market quickly without incurring significant early trial costs and risk. The last program I would like to highlight is BRI-65A, Ipatroboroli, which we license from AM2 Therapeutics for the treatment of refractory non-trabucculosis micro bacteria and also known as ANTM infections. This is life-threatening lung diseases, often affecting many patients in U.S., Japan, and China. NT Therapeutics, which is based in the U.S., already filed for their S1 prospectus and IPO registration in March 2022. Brie 658 is a novel, completely novel antibiotics product. has a potent and a broad spectrum activity against mycobacteria and many other bacteria pathogens. AN2 is developing a petrol borole as a once daily orally administered treatment for patients with NTM with the initial focus on treatment refractory mycobacterium avium complex, also known as MAC, which is a very severe lung disease. into an expected to initiate the registration phase two, three 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 apetroboroli in treatment refractory, NTM, MAC, lung disease. Our aforementioned achievement are also gaining traction in the capital markets with our addition to eight pension indexes and the Hong Kong Connect Exchange in the fourth quarter of 2021, which raises our visibility and added to our higher liquidity. We're also honored to have received more than 10 awards from prestigious media and financial industry outlet that highlights our accomplishment in 2021. Being a very small and a young BALTAC, we are pleased to be recognized for our mission to tackle the world's greatest challenges in public health. In 2022, we strive to do more. With our forthcoming inaugural ESG report, we will highlight our convictions around our corporate social responsibilities and especially those 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 and expand our business opportunities. Our pipeline is very unique and strong, aimed to change the way how patients are cared for. At the same time, eliminate social stigma rooted deeply in many communities facing public health inequities. 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, ultimately guide us in our clinical development 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 HPV clinical development, as well as COVID-19 antibiotic commercialization in China. Rajesh, please go ahead.

Okay, thanks, Lee. 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 burdens around the world. As many of you know, we have operations in both the 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 queue for HPV and introducing new cures for multi-drug and extensively drug-resistant chronic infections and tuberculosis and non-tuberculosis myocardial bacterial infections through our partnership with QPACS 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. 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 Chinese clinical operations and achievements in 2021, we are proud of what we have accomplished so far, particularly with our HPV assets. 179 and 3835. More recently, in February of this year, we completed patient enrollment in our Phase II APAC study that combines 3835, which is VIR, also VIR 2218, and 179, also called VBI 2601. Our strategy has always focused on eliminating immunosuppressants and boosting sustained immunological control. We think both elements are needed to achieve the result we want. And 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 a functional cue. Our expectation is that the top-line interim results 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 an MPA, and submit an investigational new drug application to initiate a pivotal study in 2023. Meanwhile, we are also focusing on educating internal external key stakeholders on our scientific topics, care pathways, and patient outcomes. The team in China has engaged very well with external stakeholders about the value of HPV function queue and its impact on eliminating the social stigma of HPV infections. For BREE 835, we expect to announce the safety and viral activity findings of the Phase II pre-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, VR, also is evaluating the combination of pre- H3-5 and an HPV surface antigen neutralizing antibody, VIR3434, in a Phase II study. We are working very closely with VIR to mutually agree on the proof-of-concept criteria as we have the exclusive option to license VIR3434 for development in Great China. Should the proof-of-concept criteria be met, we will likely exercise the options in the second half of 2022 and BRRR3434 into our HPV clinical portfolio, accelerate and combine our others HPV clinical candidates. For BRRR179, it has the potential to break immunotolerance to induce or restore B-cell and T-cell responses, providing a durable immunoresponse to HPV. In December last year, we began dosing non-steroidic chronic HPV subjects in the phase two combination study, where we are looking for the safety and efficacy of this novel recombinant folding therapeutic vaccine, when it is added to the existing standard of care, which is the therapy of peculated infernal alpha and NRTI. Right now, we expect to enroll approximately 120 patients for the first part of the study, which is Phase 2A, in the second half of 2022, and expect the top-line engineering results will be available in the first half of 2023. Earlier in 2021, we successfully completed our Phase 1B-2A study evaluating pre-179 conjunction with VBI, where we led the trial's kinetic design and studied implementation in AIPAC. Shortly thereafter, our data were accepted and presented at the International Liver Congress in June 2021. This promising human profile mechanism data reinforced the potential of 3179 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 the effects of this devastating disease and greatly curb the disease progression. On top of these two ongoing trials, according to our partner VA's annual report on form PNK filed with the U.S. Securities Exchange Commission on February 28th this year. Additional data from the Phase II trial of VIR-2218 or VIR-H35 in combination with speculated interferon alpha 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. We are monitoring the situation to determine any impact resulting from the current conflict in this region. Now we are moving to the COVID-19 program. Both our China and the US 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 imuvavimab and lucevimab in combination to this COVID-19 diagnosis and treatment guidelines, the newest addition for the treatment of COVID-19. The program was also part of the NIH-sponsored Global Phase II-III study allowing for inclusion of diverse patient populations and broad coverage of variants. Our ability to rapidly gain PLA in China and our pending EUA approval from the USIPA gave our teams the experience in executing a global study with high international standard. The experience and knowledge we gained going through this process both well for our future clinical studies and regulatory findings, and we hope to replicate this process even more efficiently in the future. As a small company that has been grounded with its first BLA approval in less than 20 months, we are in the process of building our commercialization team in China to support potential stockpiling and commercialization in the future. Meanwhile, we are leveraging our public-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 maintain neutralizing activity against the Omicron virus due to its high dose and exposure which is predicted to remain sufficient, significant, above their observed IC90. Our US FDA application remains under review by the US FDA and is pending on satisfactory completion of their FDA inspections of the manufacturing site at our CDMO. Given the unique nature and mechanism of EUA, we cannot predict when and what decisions US FDA will make. but we are working closely with our CDMO to respond to every regulatory inquiries. We are in active discussions with various governments 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.

Thank you, Rogers. Hello, everyone, and thank you for joining our earning call today. As Liz 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 BREAK296 and BREAK297, two novel psychiatric pharmatherapeutics 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 steroid, Brie296 is developed internally at Brie, leveraging our long-acting medicine development platform. It is administered as a single intramuscular injection. Compared to the current standard of care for PPD, which requires a 60 hour or two and a half 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 Bray 296. As a single injection, Bray 296 also provides 100% patient adherence. Furthermore, Braid 296 allows mothers to receive the treatment without any disruption of breastfeeding, 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 Braid 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 Brie296 and have established a satisfactory safety profile. We're planning to discuss this program with the US FDA to initiate two studies in patients with severe postpartum depression or in patients with high risk of developing postpartum depression, i.e., two clinical studies in PPD prevention and in PPD treatment settings, respectively. We believe that BRAID-296 has the potential to transform the paradigm of post-pandemic depression treatments, as well as, more importantly, for patients with high risk of PPD, so in PPD prevention. B8297 is a new chemical entity discovered internally. It is a GAFA-A10 positive allosteric modulator of GAFA-A receptor. BRAID-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 FDA last year, and we've aligned the regulatory and the clinical strategy to bring BRAID-297 to the first time in human clinical trial and beyond. We plan to submit the IMD application to the US FDA in the second quarter of this year and subsequently initiate the Phase I investigation of Break 297. So with that, I'm now going to turn the call over to Dr. Ancon Li, our Chief Financial and Chief Strategy Officer, to review our financial update and the business development strategy. Dr. Li, please.

Thank you, Dr. Yen. As a reminder, the financial figures I will be reviewing today are in R&D, unless otherwise noted. For 2021, our other income was $99.0 million, representing an increase of 17% compared with $84.6 million in 2020. The increase was due to additional income recognized from PRC government grants in the 2021 period. Our research and development expenses were $494.6 million in 2021, representing a decrease of 43.5% compared with $875.5 million in 2020. This decrease was primarily due to decrease in third-party contracting costs relating to COVID-19 programs. Administrative expenses for 2021 were $208.4 million, representing an increase of 101.6% compared with $103.4 million for 2020. The increase was primarily due to the increase in employee headcount. In total, our comprehensive expenses for 2021 or $4.2 billion, representing an increase of 206.2.2% compared with $1.2 billion for 2020. The increase was primarily attributable to the $3.0 billion increases in fair value loss on financial liabilities through profit or loss, or in short, FDTPL, associated with fair value increase of our preferred shares. I want to note that this is a non-cash item and purely an accounting adjustment. We do not expect additional charges like this in 2022 and beyond because all preferred shares have been converted into common shares at our IPO. Including non-cash charges and expenses and listing expenses, our adjusted loss for the period improved to $480.7 million versus As of December 31, 2021, our bank and cash balance, including restricted bank deposits and time deposits, was $3.3 billion, compared with $1.1 billion at the end of 2020. The increase was primarily attributable to the proceeds received from our security, crossover financing, and $2.8 billion in proceeds from our IPO. As our executives introduced 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 partners' global program in China and our in-house discovery program in international markets. This concludes our prepared remarks. We will now open the floor to operators. Operators, go ahead. Thank you.

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

Thank you. The participants will now begin the question and answer session. As a reminder, if you wish to ask a question, please press star and 1 on your telephone keypad and wait for your name to be announced. The first question comes from the line of Sean Wu from Morgan Stanley. Please ask your question.

Thank you very much for taking my question. Congratulations on management for all the clinical progress. And also, of course, the re-neutralizing antibodies is now part of the treatment regimen for Chinese government dealing with COVID-19. So I have, like, the first question is about, kind of, for the neutralizing antibodies. Yes. Can you hear me? So what's your expectation, like how much the government would stockpile for this? And also in the setting of prophylaxis, like many patients, actually one of my clients told me specifically, she's very worried about her elderly grandmother she may be like immune compromised that cannot take the vaccine. How your antibiotic may help her out? So that's my first question. My second question is about your HBV. This is a very hot area and it's of very keen interest to a lot of people in China who have been previously infected with HBV. So what are the major readout dates for people to see how you guys have made the progress in this together? Thank you.

Well, thank you, Xiang, for the question. Let me answer the HPV function cure question 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 VA2. So for the HPV 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, four different combinations of therapeutic options, combinations with our partner VEER. The data will read out. The data already read out with the combination of the SRA and the Paglia interferon. I think there will provide additional data hopefully at the EZO meeting in June. And then also they are conducting another combination with the SRA plus the neutralizing antibody. I think that data is also becoming available depending on the invasion in Ukraine and see whether or not that's gonna impact the data, the recruitment. And for us, as we mentioned, that our combination study, the SRMA 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 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, you know, 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 Paglia interferon therapy in the partially responded patient population, that one has started beginning to enroll and then we believe we can complete 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 monsters, and also we mentioned that we have principally agreed with the POC criteria with VEER, and then we believe that 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 or catalysts in our minds in the next 12 to 18 months. Thank you. Arjun? Yes.

So let me ask the first part of the question regarding the China commercialization. As you know, we have been actively engaging China, central government, different agencies, ever since last year. So, as you know, there are outbreaks in Shanghai and other cities, you know, maybe because, you know, have been more actively engaged with those government agencies. Since last week, since the announcement of the new treatment of COVID-19, we have been approached by more than 10 provinces and cities, governments, asking for purchase of our antibodies. You can see there's a huge demand in the local level as there are already 28 provinces have new COVID-19 cases reported in recent months. So the need is there, and we are being very actively negotiating with them. And also, you can see from the reimbursement payer part, the biggest payer is the Chinese government. Bureau for reimbursement. They have published their kind of policy and encouraging local government to list all the products in the new guidelines into their reimbursement list. As of now, we already know that some of the provinces already list our antibodies into their reimbursement list as a which is to be reimbursable. So I think in the later months, maybe weeks or months, or maybe more weeks ago in their reimbursement list. That's on the payer side. And so talking about anybody's role in the, whether athlete or immunocompromised or suboptimal responders to the vaccines, as you know that long-acting Neutralizing antibodies is an important role to enhance the immunoprotection for the people from COVID-19 infection. We know other long-acting antibodies have been approved for their prophylaxis, pre-exposure prophylaxis, and also post-exposure prophylaxis in other countries. Our antibody is also a non-acting antibody. In theory, these antibodies can also enhance their immunoprotection for the people. We currently have one study actually in National Institute for Respiratory Disease. They are doing a small study evaluating of anybody in the cancer patients and see how their injection or infusion of antibody can prevent the, can compare with not inject the antibody, compare with the neutralizing activity of the patients. So we are exploring the prophylaxis indication in China So as of now, I think we haven't gotten the indication as of now. So we are exploring now. Thank you.

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

Thank you. The next question comes from the line of from SVB Laring. Please ask your question.

Great. Hi, good morning. Good evening to everyone in China. So I have two 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, you know, I think you mentioned you were working with your CDMO to respond to requests. Are these fairly straightforward? You know, how quickly do you think you can work through those?

Yeah, so thank you for the question. I think we, you know, obviously FDA inspection unit have 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 in addressing some of the inquiries and some of the resolution to some of the observations that they have. And unfortunately, in this case, we can't really predict when FDA will take a decision or 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 inquiries are ongoing between FDA and our CDMO.

That's fair. Interesting. 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 treatment regimen?

Well, thank you very much, Anne. And I'm going to ask Rodgers to comment on that.

Yes. The new diagnosis and treatment guidelines for COVID-19 was just announced last week. Actually, we already have three kind of online training programs 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, educational activities to educate the doctors all over China, especially for those doctors working in infectious disease hospitals, which are treating COVID-19 patients, there are around 2,000 hospitals specifically designated to treat their COVID-19. So I think in later months, I would say there will be many education programs ongoing, either from the government side, also from the medical community to educate the trained doctors and healthcare professionals with the newly released guidelines. Thank you.

Yeah, thank you, Ran. I hope that answers your question. Sorry, go ahead. It does, thanks.

It does, it's helpful. Last one for me. I was curious, you mentioned your PPD program and looking at prevention as well. how do you plan to identify patients proactively here for your therapeutic and, you know, what are you going to use, biomarkers or symptoms, or how are you thinking about approaching that?

Great questions, Raina. I'm going to ask Dr. Yen to answer your questions.

Yeah, hi, Kambana Raina. 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 in terms of identifying these high risk patients, at least 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, the mother will have a high risk of PPD development in the second childbirth. In addition to the previous PPD episodes, Mothers who suffer from other depressive disorders 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 you could have as high as one in four every 25% of the mothers 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 research to identify if we could have a biochemical marker so that will more precisely help us identify these patients in the future.

If I may add, Rowena, 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 biomarker study to understand the risk of women developing PPD has become much higher. Because this is the first program ever being looked 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 deserves 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.

Great. Thanks a lot.

Thank you. The next question comes from the line of Wangbin Zhou from CICC. Please ask your question.

Hello. Hi. Thank you. Thank you for taking my question. This is Wangbin from . So I have two questions. First is about our HPV portfolio. And now we have a SMA and a preventive vaccine. And we also have the option to license a neutralization antibody called the VO3434. So since VO has disclosed early normal therapy data, so do we have any comments on this product and when we expect to license in this product? Yeah, this is my first question.

Well, thank you, Manbin, for the question. I think for the, I think the line wasn't very clear, but I believe you're asking, you know, whether or not there's any new data coming from the neutralizing antibody. I think Beer has disclosed early on, pretty much on the cohort by cohort basis, look at the anti-viral activity in the first 6 mg and the 18 mg and ascending 5 mg. I think they're pushing the dose higher to 300 mg. I believe that's the top dose they would go. I think they clearly identify a dose-dependent response, and which aided them to start designing their combination study, which they will be testing at the therapeutic doses, which is going to be at 75 mg or higher, which they believe will be the important doses. Obviously, some of this data have not been public, so we can't really disclose that. But we're looking forward to really look at both the data from their monotherapy study as well as their combination study with SRNA at the therapeutic dose. And those are the data we'll 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 answers your questions.

Okay, got it. And the second question is for our HIV product. And we passed the clinical study in last December due to the study tests that occurred in the clinical trial of HIV. Now, can you show us more information about the side effect and when we can expect our study to restart?

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

Yeah, 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 and the monthly therapies that MERT were conducting. And this was a pretty massive number of studies. So they have seen a dose dependent decline of CD4 cells. And in some of the cases, some of the doses, it was pretty significant, very profound. And which is the reason that got FDA concerned. So we believe their monthly dose, where they see significant CD4 cell discount, that one is being put on the full hold, full clinical hold. And the weekly oral combination with a novel NNRTI, the MERC 8507. That was also put on the full hold. In fact, if you look at the data, the NNRTI seems to also contribute to the decline of CD4 cell count. So we believe that regimen is going to have major issues because you not only have to investigate this electrovir, 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 .75 milligrams. 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 regimen. So that's the kind of thing that we're looking at, you know, how we're going to be able to identify a safe dose from our phase one study, which we believe we have identified a couple of doses that are within the safety margin that we believe FDA has considered to be safe. So therefore, this is something that we're going to propose to meet with FDA soon and then discuss and as soon as we can to lift the clinical hold so that we can continue the study and move into the combination study with 778 as soon as we can. So I hope to answer your questions.

Yeah, thank you.

Thank you. The next question comes from Valerie Yu from Tang Yu Partners. Please ask your question.

Hello? Can you hear me, Coley? Hello? Hello?

Yes, we can hear you.

Go ahead. Okay, thank you. I'm also hearing the lines. So my first question is regarding an update on the China government procurement negotiation process on our neutralizing the entity, since... has already purchased by Chinese government with 100 yuan per case. So I don't know whether this is kind of like a price that we think would be reasonable for us.

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

yeah yeah i i didn't hear very clearly because the line is just like uh not very clear but if i understand it right you are asking for the uh for the price um of our anybody and also comparing with their um the prices uh by this small molecule yeah if i understand it right so for our case in our case uh we have not yeah thanks We have not finalized our pricing, so we cannot discuss it at this point. For the Pfizer small molecule, we heard 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 their you know, the, the treatment window, or we can be, uh, our product can use for the patients, um, um, uh, 10, within 10 days after the, um, symptom onset and also about their, uh, jock jock interaction. We know that small molecule has a lot of, uh, jock jock interaction, um, and also about their, um, lever and kidney function with the small molecule. They have some limitations. Um, uh, furthermore, our antibody has enhanced their immune kind of protection for the patient for reinfection or getting infected with COVID-19. So roles are not the attributes of the small molecule. So we have different role to play, and I think we provide different value over the small molecule. So we got in the price, as I just mentioned. We haven't finalized our price at this stage. Thank you.

Thank you a lot. What is our progress and update regarding the new negotiations with government procurement?

We haven't come to that stage to negotiate on the pricing because it's just been getting to the reimbursement listing. As I just mentioned, the biggest payer in China It's 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 list all their products recommended in the treatment guidelines to be listed in their reimbursement list. They're 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, the coastal province. In their announcement, they already put our antibody into their reimbursement list, and it said they put the product at the 80th, which is fully reimbursed, and they are not mentioning about price. The government will pay for it. But in our case, we haven't finalized our price. But once we have finalized our price, I think it can be fully reimbursed. So that's the situation. Thank you.

I see. So we are getting the reimbursement list, but there's no exactly volume procurement schedule from the government, even though provincial government is. So we don't know the volume and we don't know the price.

Yeah, as of now, we just received, yes, as of now, because we, you know, we have already received, as I mentioned, many purchase requests from more than 10 provinces, cities. They are not, some of them mentioned about the volume. I cannot tell here. Some of them didn't mention about the volume because they said, oh, we'll, We ask for a volume to purchase our product for stockpiling. Some of them ask for the clinical treatment. So some of them has not been asking for their volume. So we cannot, as a current state, we cannot predict their volume because another factor is that as they're evolving, evolving pandemic situation in china you know see you can see that today i think today announced the numbers of new cases it's about five thousand new cases reported so it's also depending on how the pandemic will be involving right that will largely impact the volume they need thank you

Just a curiosity that normally, for example, we negotiate with the national reimbursement governments, while in our case, we're going to the provincial governments, not the nationalists. Is there any reason there?

No. Usually, the mechanism is usually that national negotiations happen at the end of the year. We're 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. Our products are not currently commercially available at this stage. So usually the port has, you know, if you're looking at their traditional kind of negotiation on price, The product has to be on the market, has to be approved, and the negotiation always happens at the end of the year. For the Pfizer small molecule case, it's even very special. I think what we heard is that the central government has a 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 the newly released treatment guidelines, there are only two products listed in this antiviral, specific antiviral treatment. One is the small molecule and one is our product. So I think probably in the future, there will be some negotiations. 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 because of the emergency.

Yeah, and my last question here is could you please update the manufacturing capacity target for 2022?

So for the manufacturing capacity, we are actively working with our CDMO to scale up the capacity. But it also, depending on their commercial order and the government stockpile, and also the involving of the pandemic. But I think if there is a need in the market, I think there will be a solution. should not be a kind of problem because if you're looking at how much inactive vaccines China produced, it's about 5 billion doses, right? I think that's of course on the Chinese government's fully support to support to control the pandemic because it's very special cases. I think in that case, if there is huge demands I think other stakeholders like the government or other stakeholders were seeking, I think, support to meet the urgent needs of the market.

Thank you. It was knowing that we have around 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 will be a new year, so there's more capacity from them, this number will be increased?

I would say it's very depending on, as I just mentioned, it's very much depending on the commercial order and the government. I just can't tell about that much. Okay.

Thank you so much. I appreciate it.

Thank you.

Thank you. The next question comes from Edison Kong from Haitong International. Please ask your question.

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

Thank you. Thank you for taking my question in the last minute, sir.

And so I have one question for program 297. It's a very interesting, challenging area in depressive disorders, I believe. And I want to know more about the research, because I believe there's another job for benzodiazepines, which is a short-term and off-label use in also depressive disorders targeting GABA8. So is that just a similar version to this of label just, or is it different? In what way is it different? Thank you.

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

Yes. As I mentioned, Br8297 is a new chemical entity that we discovered internally. And it is a GABA-A PAM, so it's a different class of molecules. It acts on both intra and intrasynaptic, so it has a different mechanism of action as compared to the off-label as a benazone 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 components 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 to develop, 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, you know, there are more than 10 different indications. So we think it's related to various depression, depressive 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, improved clinical features allows us to have a lot more flexibility to address all those indications. Now with that, I think let's wrap up this call and I want to thank you all for joining this call. I know we're a bit 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 one person alone, no one company alone, no one country alone, or no one university alone can deal with this all together. This obviously requires all of us working together, including the investors investing in companies like us, because we are going after a major public health issue that making the public safer in which we all reside. So I really appreciate the genuine support. I know sometimes you felt that we have not given you the full answer as much as we can. The reality is, you know, there's a lot of uncertainty with a lot of the, you know, 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 zero COVID into a more sophisticated integrated tools to address the pandemic, which we've been educating the government along 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 is just not going to be about how we control the pandemic through isolation and quarantine and diagnosis. And I think for us to 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, in your investing hypothesis, but we do believe that by helping a company like us, we are doing a huge deal for the society. I hope at the end of the day, you walk away with that thought in your mind. We should not be alone here dealing with this. The government must and should step up to help and then obviously various government at 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 thank you for your continued support to our company. which is truly a great company, Cosbreed Biosciences. Thank you very much.

That does conclude our conference for today. Thank you for participating in all these connects. Have a nice day.