Good day, ladies and gentlemen. Welcome to CANbridge's LIVMARLI Mainland China approval call. It's our great honor to have the following management with us here today: Dr. James Xue, Founder, Chairman, and CEO of CANbridge Pharmaceuticals, Dr. Gerald Cox, Chief Development Strategist, Marcelo Cherksey, Chief Commercial Officer, and Glenn Hassan, Chief Financial Officer. Management team will give us a presentation on the latest company development, and then we're going to have the Q&A session. I will hand over to James to start the presentation. Thank you. Thank you, host. Good evening, good morning, everyone, welcome to the LIVMARLI Mainland China approval call. Next, please. We will have the part parts of this presentation, with a overall introduction from me and the clinical data label introduction from Dr. Gerald Cox, and the commercial strategy from Marcelo Cherksey, and an upcoming milestone from Glenn Hassan. Next, please. This is the forward-looking statement. As you are familiar with CANbridge, we have been focusing on developing and commercializing life-changing therapies with a foundation in China, with more exclusively for focusing on the rare disease space. CANbridge has been led by a very seasoned global management team. Each of us have more than decades of experience in the global biotechnology development, commercialization space, and we are definitely considered a leader and a pioneer in the rare disease space in China, where we have established a fully integrated operations from research, development, manufacturing to commercialization. We have also built an impressive and diverse portfolio that deeper than, you know, most of our peers in this relevant space. Currently, we are also undergoing a transition from a biotech stage to a biopharma stage with multiple commercialized products, as well as pivoting from a China focus to a global player. Next. Here is just a glance of our very comprehensive and diversified pipeline. Today, LIVMARLI is one of the products that listed on the top. As you can see, that most of them are what we call, you know, in China, for China, that we own Greater China rights. Our goal is to really leveraging the data outside and inside China, and to allow us to accelerate the market approval to meet the dire and medical need. In this case, LIVMARLI, also known as CAN108, has been a product that we partnered with Mirum Pharmaceuticals and is a unique product addressing several diseases, what we can call a pipeline within a pipeline. Alagille syndrome, Progressive Familial Intrahepatic Cholestasis, PFIC, and biliary atresia are the three indications that addressable by this drug. Alagille syndrome will be the first of the three to get market approval in China. Next. We're very excited that LIVMARLI, we also have provided a Chinese trademark name, [Foregn language]. It is the first and only approved therapy for cholestatic pruritus in ALGS, and it is an oral solution with minimum absorbing and is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome, 1 year old and older. This product is considered a new class novel product, then address a population over 12,000 patients in China. Our partner, Mirum Pharmaceuticals, has recorded $68 million sales in net sales in the first full fiscal years of launch in the U.S. Based on the track record, we're confident that we also can build a strong commercial foundation for LIVMARLI, starting with ALGS. Next. Now, Dr. Gerald Cox will give the second part, label and clinical data. Thank you, James. Next slide. Alagille syndrome is a rare genetic disorder that involves multiple organ systems. One that is particularly prominent in the hallmark of the disorder is cholestatic liver disease, in which there's a backup of bile into the liver, which includes bile acids that damage the liver and cause inflammation. The buildup of bile and bile acids in the body leads to a number of very debilitating clinical symptoms that diminish the quality of life of patients, and among these is pruritus, or severe itching, to the point where patients are bleeding from itching, and they can't get to sleep. They can't stay asleep at night. It really diminishes their quality of life. In addition to the pruritus, and the impact on sleep, it can cause fatigue, it can lead to suicidal ideation, and in some severe cases, where there's such a diminishment of quality of life, the patients may actually receive a liver transplant to relieve the itching. The disease can involve progressive liver inflammation and cirrhosis, such that there is about a 10%-35% mortality rate over a 10 year-30 year period. Next slide. Till now, there really has been no effective treatment for cholestatic liver disease, and the symptoms of pruritus, growth deficiency. There have been a couple of treatments like bile acid sequestrant drugs, or cholestatic drugs that have been used, but they really don't alleviate the symptoms very well, and the quality of life is still very diminished. In fact, in the clinical studies with LIVMARLI, nearly all the patients were already on pruritus treatment medications, but really still very symptomatic. Most patients, if they survive during childhood, they either require a liver transplant or may not make it to adulthood. Many of the patients will have, as I mentioned, very severe itching, about half the patients, to the point where they do bleed or it interferes with sleep at night. Next slide. So this is the summary of the LIVMARLI label. It's indicated for patients with Alagille syndrome, who are at least one year of age and have pruritus related to cholestasis. The drug is administered once a day, half an hour before eating. The dose begins with half a dose each day for the first week, and then titrated up to a full dose of 380 micrograms per kilogram. It's a liquid with an easy-to-use dispenser that's administered based on body weight. The warnings and precaution. There have been a few patients that have developed liver test abnormalities. The gastrointestinal adverse reactions are fairly common related to the mechanism of the disease. Because fat-soluble vitamins depend upon bile acids for absorption, in some cases, the patients may have preexisting fat-soluble vitamin deficiencies, which can be exacerbated on treatment. The most common adverse reactions are related to the GI system, so diarrhea, abdominal pain, and vomiting are the most common, followed by nausea, vitamin deficiency, and increased transaminases. There is no REMS for this product. Next slide. Alagille syndrome clinical program has involved 86 subjects enrolled across five different studies. The main endpoint of the pivotal study was a reduction in pruritus or itching using an observer-rated score from a caretaker. The pivotal study lasted 26 weeks, with an initial run-in period, during which patients all received LIVMARLI, and then there was a four week randomized withdrawal, where patients received LIVMARLI or placebo to get an exacerbation of the symptoms, and then they all went back onto LIVMARLI again. During that four week time period, the difference in the itching score on a five-point scale was 1.7, with a meaningful difference being a change of at least one. There was quite a significant change in pruritus during that four week time period. Next slide. This shows you the time course of the itch score, where this is looking at the mean change. The score of zero is no itching. A score of four was very severe itching, and it goes, you know, from 1- 4, sorry, from 0- 4, it's either no itching, mild, moderate, severe, or very severe. You can see a 1-point change really does correspond to a significant difference in the amount of itching. In this case, you can see within the first few weeks of treatment, itching is decreased by at least one point in both groups until week 18, then they undergo the randomized withdrawal. The patients who continued on maralixibat or LIVMARLI had no change in their itch score, whereas those who went onto placebo showed a spike indicated in red, with a significant worsening of their itching, which was then relieved once they went back onto LIVMARLI. Then you can see over the long term, you know, out to about four years of treatment, the itch score continues to go down gradually, and it's sustained over time. With the reduction in itching, these patients were also documented to have a reduction in serum bile acids, which are believed to play a role in the itching. Some other endpoints that were looked at that showed positive trends but were not statistically significant, included reduction in xanthomas, which are these raised lesions caused by cholesterol accumulation. Quality of life improved, height accelerated as well. Next slide. In terms of safety, this is a drug that is administered orally, and it acts within the intestines. Most of the adverse events that we see with drug treatment do involve the GI system. Diarrhea, abdominal pain, and vomiting are the most common adverse events, followed by the others listed on this slide at a much lower rate. Most of these were mild or moderate and tolerated over time. In terms of serious adverse events, there were three episodes of vomiting that required hospitalization for rehydration. Again, I think with education, the importance of hydration and dose adjustment, if patients are experiencing symptoms, should alleviate many of these adverse events. Very few patients discontinued during all the clinical trials, or just three, for liver function tests, abnormalities, and there was no impact on the QT interval as well. Because it's a drug that works within the intestine, there's very minimal systemic uptake, and so relatively free of systemic side effects. Next slide. The endpoint of itching reduction was the main endpoint looked at in the clinical trials that led to the approval, supported by a reduction in serum bile acids. Over the longer term, we are looking at other meaningful endpoints. We know that the accumulation of bile acids and bile in the liver can cause liver damage. There is a registry called GALA, which is the Global ALagille Alliance, that has looked at event-free survival over time. In the over 469 patients that were evaluated for liver transplantation, biliary diversion surgery, liver decompensation or death. In the upper right-hand side, you can see the curve in red for the natural history of disease, and then comparing that to the study patients receiving maralixibat. You can see a separation of the curves with better event-free survival over the long term. Again, this is real-world evidence data. This is not in the label, and we're not promoting this as a survival benefit, but we just wanna mention that there is additional data that's being accumulated that could point to the importance of lowering the serum bile acids on liver health. In addition, patients who have cholestatic liver disease often have growth deficiency, and Alagille syndrome is no different. The patients are often very growth restricted during childhood. Again, looking over the long term, the effects of growth in both height and weight, there appear to be a improvement in the relative growth rate of patients, where we look at this as a Z-score, which is the height relative to the height and weight relative to patients of the same sex and age. On the lower right-hand panel, you can see that the height Z-score at the start of treatment was about minus 1.7. This corresponds to the, about the 20th percentile, and by the end of treatment after 4 years, the Z-score had improved to minus 1.3. This represents about a 0.4, 0.5 acceleration in growth, height. Similar but smaller changes were seen with the weight. I think overall, you know, the studies did focus on pruritus, which is a very meaningful quality of life indicator. We did see reductions in the key biomarker of serum bile acids, and now going forward, we're evaluating some other potential benefits, including event-free survival and growth. Next slide. With that, I'd like to turn it over to Marcelo for the commercial strategy. Thank you, Jerry. Good morning, good evening, everyone. Move to the next slide, please. We see the China market potential for Alagille syndrome to be between $100 million and $150 million, and we see all three indications for LIVMARLI between $200 million and $250 million. This is a reflection of the numbers below. There are 22,000 potential target patients for the three indications: Alagille syndrome, bile and biliary atresia in China, and that's represented in the lower left with these dots that represent each of the three buckets of diseases of the indications that we have. We position LIVMARLI in China as novel treatment to decrease serum bile acid, reduce pruritus, and improve quality of life for patients living with cholestatic liver diseases, specifically Alagille syndrome in this case. I would like to point out that this pruritus, as Jerry was mentioning, it's much more deep than just the word. It includes itching, it includes bleeding in the patients, it could include sleep deprivation, and the quality of life also could include suicidal ideation. Also, Jerry mentioned that potentially there is a growth aspect for the patients living with Alagille syndrome that could be changed, which we are actively exploring. Specifically, now that with the recent approval of an innovative therapy for the Alagille syndrome, the pediatric gastroenterology community is starting to work on updating the cholestatic disease consensus, and we can facilitate and will facilitate the process by providing data to the society. Can we go one more slide, please? This consensus, among other activities that CANbridge is pursuing, has been pursuing, would lead to a change in the standard of care, as we see in the first column. Of course, we have already been working on disease awareness and patients diagnosis and identification, during the last year and a half. At this point, getting LIVMARLI as a new standard of care would further raise the interest of the healthcare professionals to get more education about Alagille syndrome, increasing disease awareness, and this would also further increase their interest in looking for new patients. We go to the next slide, please. Now, the classic three stakeholders that we're targeting is the physician, the patient, and the payer. In the case of the physician, we just mentioned, this facilitation of the update of the cholestatic consensus, and that's an activity that we will help the medical community, specifically the pediatric gastroenterologist, on this. Now, once that's done, we would incorporate this also in the educational, medical activities that we're doing, that updated consensus and in general, the education that we have been doing, about disease, about product, now that it's approved too. We also work in a not so traditional ways of commercializing and marketing, which is a virtual rep. This is a concept that helps us reach communities that are rural and that reps would not have access to, or that would be very inefficient to access. We work with this virtual rep concept for these distant communities. This is a concept that we have been using also during the COVID-19 epidemic, where the face-to-face interactions with the healthcare practitioners was not possible. On the patient side, we have a CamCare expert group. That's CamCare is a platform that we developed to have patients in a registry. We have been using this for Hunterase, MPS II. That's a previous product that as James initially mentioned, it's in the market, and we're using this same type of platform where we are creating the registry for the Alagille syndrome patients. We are also supporting the Alagille syndrome patient community as is natural, and the Alagille Syndrome Day, which is January 24th, we're also supporting those initiatives. On the payer side, we are working on submitting to the NRDL in July. And we're gonna get a little more depth on that process, but we expect to start negotiations during the second half of the year with NRDL. We have if that part of the process doesn't end up working in the short to medium term, we have a bridging plan to work on a multi-layered funding system, which is mostly based on commercial insurance. We go one more slide, please. Basically, we see a potential of 10,000 patients with Alagille syndrome in China. Currently, in our database, we have 450 patients diagnosed. Of those patients that are diagnosed, you need to exclude, according to our label, the patients that don't have pruritus. We also, with the current label, we need to exclude the patients that are younger than 1 year old. That takes us from the 450- 300 addressable patients. We estimate that the year of launch in 2024, we're gonna have around 300 patients on treatment. This will be done with 12 sales reps that will be in the field, mostly through face-to-face interactions with physicians. Again, in 2024, they will be covering 98 hospitals and around 300 healthcare physicians. The initial year, in 2024, the sales reps will also be helping with getting into the hospital listing. After the NRDL, we need to get into the hospital listing. The first year, the efficiency of the sales rep is also sometime dedicated to getting to the hospital listing. We go to the next slide, please. In February 2022, we started an early access program in Boao, in the Hainan Province, to provide local physicians with local experience and get some patients with the option of an innovative therapy that was not present in the country. At the end of May, we got NDA approval in China, that allow us to, in July, submit for the NRDL. The negotiations with the NRDL are expected to take the second half of the year, and we would know at sometime in November, early December, the outcome of the inclusion in the NRDL. After that, there's a period in which we need to get in each of the hospital listings. We expect a commercial launch in the first quarter of 2024. We will also work until we get to Q1 on the updated treatment consensus. By the beginning of Q1, we should have that updated consensus. We can move to the next slide, please. Glenn, please. Yeah. Thank you, Marcelo. I'll just go through a couple of really exciting upcoming milestone for the company. Next slide. Just on the LIVMARLI, now that we have approval for Alagille in mainland China, as well as, you know, obviously with Mirum in the U.S. and EU, we continue to work to bring this product to other market within our region. We file in Taiwan and Hong Kong, and we estimated that we will get an NDA approval over the next 12 months. I think this is very exciting for the patient in this region, so we look forward to bring this product there. In terms of PFIC, as we know, Mirum has filed their sNDA with the FDA. We did already a pre-NDA meeting in May, and we look forward to also submit the NDA in Q3 2023. This is faster than the Alagille. I think for indication expansion, we were able to file the NDA not having to wait for the approval in the U.S. In terms of the biliary atresia, as you may know, phase 2b EMBARK study has completed enrollment as we announced recently, and we expect the top line. This is already also announced by Mirum, in the second half of 2023. With this, given that we have a proportion of the study, of the cohort, is coming from China, Chinese patients, we expect to file the NDA around the same time as the global filing from Mirum. Next slide. Aside from LIVMARLI, I think I wanna point out, we have also two key near-term data readout that's very exciting. I just want to remind everyone about our CAN106. This is our long-acting monoclonal antibody against the C5, and we are looking forward to share with you the phase Ib. It's a multiple ascending-dose trial in PNH patients. I think by the time we read out this data, we will have a full, complete picture of the profile of our CAN106. This is coming in the next 6-8 weeks. The second one that I want to point out is our CAN008. This is anti-CD95 for glioblastoma. We started the trial early last year on frontline GBM, and we look forward now we have the event has already been reached, so we are waiting for the DSMB to tell us the result. We have an interim look, and I think the timing on this will be also in the next six to eight weeks. Next slide. We have two key data readout. We have a lot of progress. We've made a lot of progress with LIVMARLI. I think the company has been progressing really well, and we have done a lot of work. Ahead, we also have multiple catalysts. We have three key data readout, as I mentioned earlier. We also have multiple NDA filings expected in our region. I think we look forward to continue to bring, you know, further life-saving products to patients in our region. I would like to turn it back to James for a closing remark. Thank you, Glenn. Yeah, it's been a very exciting journey for CAN008 or LIVMARLI in China for the past two years. I want to remind us that we filed NDA application in January of 2022, only four months after the U.S. approval of LIVMARLI in ALGS, and only 15, 16 months later, we got an approval. This is quite a demonstration of CANbridge's commitment to the partnership and to the patients in our region and our regulatory experience and expertise by leveraging the global data and getting the market approval at a minimum time and cost. Now, our focus definitely is shifting, you know, from the approval to the successful launch of LIVMARLI in Alagille syndrome in mainland China. We also anticipated additional markets like Hong Kong, Macau, and Taiwan to gain such approval in the near future, as well as we are preparing for the NDA application submission for the full-on indications as we continue to progress. We would like to use the remainder of the time to entertain any questions you may have. Thank you very much. Host, you may proceed with the Q&A session. Thank you. Thank you very much, management, for the presentations. We've now come to the Q&A session. Please make sure to change your name on Zoom to the format of your personal name, plus your institution name for easy identification. If you have any questions, you can click the Raise Hand button, and you will be placed in a queue. When the host announces your name, please state your name, the institution you belong to, and then you can ask your question. You can also type your question in the chat box, and we will read it out for you. Once again, please feel free to raise your hand or type your questions in the chat box. Okay, first question from the chat box: What's our expectation of the first-year sales and sales uptake? I'd like to defer this question to Marcelo. Sure. The first year, as we mentioned in the slide, we're expecting 300 patients on therapy. What we are calculating is that by 2033, we're gonna have between $100 million and $150 million in revenue. We are, yeah, we are learning that from our experience with countries in China and from the experience that we have in rare diseases in other geographies when the first product gets to the market. If I can add, I think, the first year, it really depends. As you know, we are still in the process of an NRDL. We are not giving, in terms of pricing guidance at this point. You know, I think we are comfortable that we can reach 300 patients, given the patients that we identified so far. I think, you know, I think The first year, let's see. Let's see after the NRDL. We're comfortable with our peak sales 10 years from now. I think it is representing a tremendous market for us, and we're excited to bring this product to patients. Thank you for the management's response. Our next question is: How confident are you with the timelines to get product imported, and that you can begin an NRDL negotiations this fall? We're very confident, with the NDA approval in May, we're very confident that we can get into the NRDL submission for sure, and negotiations with a competitive price that would be beneficial for the patient community to have access and for us to maintain a sustainable business. Regarding importation, we are also very confident that we'll get the product on time in China for the Q1 launch. Thank you. Well, I just want to add, you know, our partner, Mirum, currently is controlling the manufacturing. We have been working very closely with our partner throughout the entire process of NDA review and approval, so that we can synchronize, harmonize the procedures for the release of the product, you know, the labeling, and then, of course, the ultimate importation process into China. What Marcelo just said is just, you know, the confidence resulted from that kind of intimate interactions and communications and coordinations with our partner, Mirum. Thank you, management. Next question from the chat box again. Do you have any competitors in China right now? If yes, is there any difference on drug efficacy? Sure, I'll take that. you know, the standard of care, as I mentioned, really involves these bile acid sequestrant binders and cholestatic agents, but they just don't work very well. In fact, you know, 90% of the patients who participated in the pivotal clinical trial were already on one or more of these anti-itch agents. I would say that in terms of efficacy, there really is nothing that compares with LIVMARLI in China. The current version of the ALGS treatment consensus outlined the only option that other than LIVMARLI is the nutritional adjustment for the patients. There's no other therapies available outside LIVMARLI. Thank you. Our next question is: Will you be outsourcing the sales, or will you do it on within your own team? We'll be doing this with our own team. As mentioned in the slide, we will have 12 reps, initially covering 300 doctors. That's what we initially are planning, but as after any launch, and you know, that you start retargeting and resizing. We don't rule out that we will have a larger sales force after the first year. Yeah, it's gonna be totally with our own team. We will also have a, in the field, six people related exclusively to access. The reps will be mostly to educate physicians and to find patients, and at the beginning, to get the product in the hospital listing. We also will have an access team that will come to improve the... all the stakeholders that are related to the access of the product in each, region and hospital. Thank you, management. Once again, if you have any questions, you can click the Raise Hand button, and you'll be placed in a queue. Alternatively, you can also type your question in the chat box, and we will read it out for you. Do we have any more questions? Okay, we will now hand over to James once again for some final remarks. Thank you. Thank you, host. Definitely, I'd like to thank the team for their hard work, our partner, Mirum, for their commitment to this partnership that allow us to have LIVMARLI approved at the earliest date. Also, I'd like to thank you for your listening and your questions, and your follow-up with our operations in this area. We do have a Mandarin session on the same subject about 12 hours from now. You know, you're welcome to tune in again, and we very much look forward to continue to working with our partners to have a very successful launch of LIVMARLI in mainland China and then other markets follow on. Thank you very much for your tuning in today. Thank you, James. Ladies and gentlemen, that does conclude our presentation for today. Thank you all for participating. You may disconnect now.