Thank you for attending Jefferies London Healthcare Conference. My name is Kelly Shi, one of the senior biotech analyst here. In this session, please join me and welcome the IR team from HUTCHMED, David Ng, Head of IR, and also Annie Cheng, also from IR team. And, welcome both. Thank you. Maybe to start off, can you give us a brief overview and the strategy of HUTCHMED before we get into details of the pipeline? Sure. Thank you. Thank you, Kelly. Thank you for having us. So, I'm David Ng from HUTCHMED. We have been a small molecule self-discovery company for many years, more than 20 years, and we have already three products successfully commercialized in China. And I think the most notable event recently is that we just have our U.S. FDA approval for our colorectal cancer drug just last week. And Takeda is our marketing partner outside of China. They will commercialize this product in the upcoming years. Now, beyond that, we also have a pipeline of many other small molecule drugs in various stages of development. We also have a drug for lung cancer that we have commercialized in China, you know, aiming also for, you know, bringing it overseas and, many other drugs. So, the other thing that I think we distinguish ourselves from other biotech companies in China is, you know, we aim to run a profitable business going down the road. So two years from now, we aim for breakeven. We have a very, strong cash balance of around $850 million at the end of June. So we don't need near-term capital market activities and can continue to sustain our growth and, and business, and, as well as our discovery going down the road. Terrific. Maybe we can start talking about your commercial products in China, given you have a very strong focus and also presence in oncology market in China. Could you talk about the new dynamics you think investors may not be aware of? For example, the NRDL inclusion and also the price trend, and also the anti-corruption campaign in China. Sure. So two, two very popular questions that we have encountered from investors recently. So maybe first on anti-corruption. I think the, y ou've all seen kind of the big campaign in July, August, but things start to have stabilized a little bit entering, you know, October. So you know, of course, this is all for the, you know, ultimate, good, healthy development for the healthcare and the drug development industry. And we also think that this is actually, ultimately beneficial to companies like us, which focus on innovative drugs. So we, we compete on efficacy and toxicity, rather than other, other stuffs. So, the impact on us for, you know, for HUTCHMED is quite limited. We adhere to very strong ethical practice in our, you know, sales and marketing behaviours. Now, for the overall industry, I think the impact may have already peaked in third quarter this year. And entering in Q4, the overall industry sales seems to pick up a little bit. So we welcome this, and we continue to think that, you know, we are in the right track of doing innovative drugs, and that should put us in a more favorable position. The second thing is the price cut. So, as most of you know, to be included in the government insurance program, we need to negotiate the price with the authorities. We have already done that for all three of our drugs, which we have commercialized in China. For our very first drug back in 2019, yes, the cut was quite severe at around 65%, but it has again moderated quite a bit. The latest drug, which we have i n late 2022, the price cut is around mid-30%. So I think the authorities have definitely recognized the importance of the innovative drugs development in China, as well as the R&D that is needed to support this, as well as, I guess, the end market pricing and profitability for this drug to continue to support this industry. So I think we expect sometimes this policy may have overshot a little bit, but, you know, after a period of time, the authorities have improved in their implementation, and I think this is sustainable. I think this is a adaptable price trend that we can live with. So, yeah, we will continue to invest in R&D. Our headquarters in Shanghai, we have a team of 900 scientists. We will continue to develop innovative drugs, and we will continue to bring it to commercial market in both China as well as to overseas. Super helpful, and, maybe let's start with fruquintinib, which is a pan- VEGF inhibitor, and, congrats on the FDA approval of fruquintinib, which was two weeks ahead of the original schedule. And, when should we expect the drug to be officially launched in the U.S., and how will fruquintinib be priced? I don't know if you can talk about the, this, this topic, and also, your partner, Takeda's, commercial launch readiness and strategy. Great. So this is great news, and, you know, if you noticed our stock, that has definitely one of the factor that has been driving our performance the last few months. And we think this is the beginning of many more commercial products we can bring to the overseas market. So as far as I know, I think the first script already written a few days ago. You know, the Takeda team has been very efficient and actually has been ready, standing by, ready for this. You know, despite the fact it's a couple of weeks earlier than the original PDUFA deadline, but they are quite ready, and they will continue to, I think, do a great job in selling this. Now-... Regarding pricing, it is a big multiple versus China. As I've mentioned earlier, the price in China had gone through price cut, you know, last few years. So in China, it's running at around $1,000 per month. But, you know, for the U.S. pricing, it's like many, many multiples above that. So that does present a very important source of revenue for us in the coming years, as we now get the approval in the U.S., and we are also aiming for further approval in other jurisdictions. So in Europe, hopefully, you know, around the middle part of 2024, and for Japan towards the later part of 2024. And these are all going to be, you know, under Takeda's efforts to continue to expand this. In terms of other potential clinical indication, there's no particular disclosure yet, but we can refer back to the original deal sign that we signed with Takeda early this year is $1.1 billion, and we collected $400 million upfront early on, and then another $35 million triggered by the FDA approval. So, you know, just on the size of this deal, you can infer that the expectation is also quite high for the ultimate sales of this product, whether in U.S. or rest of the world, or whether in currently approved colorectal cancer, third line, or maybe even other further indication. Yeah. Okay. And turning to the commercial outlook you touched upon, and we have a high expectation. Maybe you can talk about, based on the profile of the drug, what are the most suitable patients likely to benefit from fruquintinib and also put a market size on that? And also, do you see potential for the drug to move to earlier line in CRC? Yeah. So, you know, we and this is another thing that we are very proud of, right? So we've done this clinical trial in China, you know, many years ago, and we saw, and we saw very statistically significant improvement in both PFS as well as OS. And then we do another trial overseas called FRESCO-2, and we basically almost repeat the same improvement for overseas patient. And when compared to some of the existing therapies on the market, which may have a PFS of, you know, shorter than two months, we are almost approaching four months. So from the efficacy perspective, we are very proud, we're very confident that this will be a very compelling choice. And also equally important on the toxicity profile, we don't have any black box warning on our label. We don't need a lot of, you know, the blood draw for, you know, you know, monitoring on a regular basis. So on the, on the toxicity profile, we are also very proud that this can be a very good option to patients in the third line setting. We haven't done anything major in moving to an earlier line. We, you know, we do see out there, we have a lot of so-called investigator trials trying to, you know, explore different options, but at this stage, we haven't done anything formal to move to earlier line yet. In terms of the peak sales potential, Takeda hasn't disclosed anything, and, you know, maybe it's not appropriate for us to do that, but, you know, out there we do have a lot of analysts with very good assumption about the peak sales for this indication. Okay, terrific. What is the next step of developing fruquintinib into additional indications in both U.S. and the China market? Yeah. So China, the plan is much clearer at this stage because we have been working on this last few years as well. So apart from the third line colorectal, which is already commercialized, and, you know, by the way, we do actually have very nice market share of close to 50% of the market in China in third line colorectal. We are expanding into gastric cancer. So the pivotal trial already completed for China. We have already sent the data to the regulatory authorities in April this year. So if everything goes smoothly, there's a possibility that we can get a new indication approved for China in second quarter next year. Mm-hmm. And this is important because, you know, by bringing this therapy to the gastric cancer patient, we also estimate that the market size of gastric cancer second line is at least two times that of colorectal cancer third line. So it's a very solid addition to our market potential. And then we are also exploring usage in combination with PD-1 in endometrial cancer, as well as in kidney cancer. So these are all happening in China in very advanced stages of development, and we quite confident that, you know, they will continue to add to the market potential in China. Again, for overseas, we await further disclosure from Takeda in terms of their strategy to pursue different indication beyond colorectal cancer. Okay, so very sizable opportunity. Maybe moving to savolitinib, which is a c-MET inhibitor, and this is AstraZeneca partnered molecule. Maybe could you actually give us an update on the clinical trial progress and also the targeted market and the size of the market? Yes. So again, this, this product already commercialized in China, but for a smaller, you know, subset of lung cancer patient, called MET exon 14. But we are definitely aiming for bigger indication in the second-line usage for lung cancer, non-small cell lung. We are doing clinical trials both concurrently in China as well as overseas, and of course, overseas trials are carried out by AstraZeneca. So, I think for next year, watch out for this trial to have potential readout of data. This trial is called SAVANNAH. So people who may know HUTCHMED for quite some time will definitely have heard of this name. We focus, of course, on the MET-high, like this biomarker-high patients subset, and we've seen in previous data analysis that we can have very good improvement in the PFS. We want to also stress that, you know, this strategy of combination with T, both are oral pills, are much more convenient and I think, you know, provide better quality of life to patients than some of the other alternatives. Like, I mean, definitely this is a space where a lot of competitors will continue to develop innovative products. But, you know, we are very confident that, you know, this combination strategy works. And, you know, it's a very obvious extension of AstraZeneca franchise in TAGRISSO in the second-line space. Towards the end of next year, data readout for SAVANNAH in this MET high population. We will try to aim for so-called accelerated approval from FDA and then filing towards the end of next year if everything goes smoothly. Okay, great. And, at a recent ESMO, I'm sure you're aware of, Genentech's MARIPOSA and the MARIPOSA-2 trial in the non-small cell lung cancer in EGFR mutant space in both front line and the second line. And, do you think the outcome actually has impact on the development plan of, savolitinib and also TAGRISSO combo- Yeah. Also, the future plan moving to front line? Yeah. So I think, you know, maybe two major takeaway from this. Number one, if anything, it should also incentivize AstraZeneca more to speed up this development of another strategy for second line. And again, you know, it's a combination of their own product. The other takeaway I would say is, if you just look at the second line scenario, you know, the, it's a three-drug, right? It's like a bispecific, it's another TKI and then chemo at the same time. And so far as, you know, the details that have been disclosed, it also requires some prophylactic anticoagulant prophylactic treatment before the therapy. And of course, you also have the potential side effects and also the toxicity of chemo. So, you know, again, of course, at the end of the day, it will be down to the doctor's choice, right? If, you know, if first line is already solidly, monotherapy with TAGRISSO, then second line, if there's a choice of, like, still TAGRISSO plus our savolitinib, both oral, with less toxicity than a chemo triple therapy, I think it's still going to be a very compelling choice. Now, of course, you know, right now it's very, academic, right? You know, because, you know, the products are not approved on the market yet. But at least from the efficacy data that we have seen so far, from the, toxicity data that we have seen so far, we continue to believe that our combination strategy with TAGRISSO is, is a very, you know, good alternative to, to patients. So, yeah, so I think, you know, we don't worry that much, especially in the second-line scenario, and we continue to think that, you know, this is a very good choice for patients. Great. Maybe you can remind us how big the market is in the post TAGRISSO non-small cell lung cancer settings. What percentage of the patients actually have a MET aberrational application and could be addressed by savolitinib? Sure. So, there are different statistics from different studies. In our study, the percentage is quite high. You know, we've seen some other publications saying that maybe 30% in the second-line scenario, MET positive. In the study that we have done in SAVANNAH, is as high as, like, 60% for second line, and actually within that half, MET high, more than half are MET high, and the other is MET low. So we think that you know, this is still a very sizable market out there. Whether it's the 30% or the 60%, it's still very high percentage out there in the second-line scenario. And again, this may be another interesting thing and to be determined, right? You know, our trial focus on MET-high patient, whereas some of these competing products are all-comer, right? So, you know, if ultimately our label or you know, potential approval can be obtained for this subgroup of patients, I think that will be, again, a very compelling choice for the doctors, you know, for the MET-high patients. Terrific. Maybe switch gear to the autoimmune pipeline candidate, oral Syk inhibitor, sovleplenib. Hope I pronounce it right. Yeah. You have announced the drug met a primary endpoint of durable response rate in second-line ITP, immune thrombocytopenic purpura in China. Can you talk about the regulatory timeline, and also what is the estimated market size? And does this also reflect HUTCHMED has aspiration to move beyond the oncology market and also to other therapeutic area? Right. So, thanks, Kelly. So we announced back in late August that the study in ITP, the phase III study in ITP, hit the primary endpoint, and we're looking for an appropriate scientific forum to disclose the quantitative data as per our usual practice. So how this came about is that the mechanism is ultimately inhibition of Syk, which ultimately inhibits B cells, and that was our original point of research, looking at B cell lymphoma. So it is scientifically adjacent. It was a natural evolution then for us to look at this very effective B-cell inhibitor and say: Where else could this go? And ITP is a natural place for us to investigate. In terms of other potential applications, you know, B cell inhibition has shown to have an effect in other autoimmune indications. So, we will definitely be evaluating that. And I guess in ITP, there's limited treatment options to address the underlying cause of disease, which is immune-mediated destruction of platelet cells. So, there are therapies available that can promote the production of platelet cells, but very few options that are quite effective in terms of normalizing, if you will, the disruption. So, emerging agents in this space are actually focused on that and actually also looking at B cell inhibition. So, you will have an opportunity to do cross-trial comparisons to see with other agents to see how our Syk inhibitor performs. You can also maybe take some inspiration from the other programs that are being pursued by these other agents. We'll do what's logical and sensible, of course. Okay, great. And any other, clinical stage candidates you would like to highlight from HUTCHMED? So actually, around the end of the year, we're planning to file sovleplenib in China. We're also planning to file for another B cell inhibitor, tazemetostat. So this one inhibits another node in the pathway called PI3Kδ. So we have completed a phase II registration-enabling study in third-line follicular lymphoma. And we will make a decision, probably will move forward with filing that study with the authorities in China, either late this year or early next year. Terrific. And lastly, would you like to share your insights on the corporate development strategy of HUTCHMED? And talking about going global, so far you've formed a pharma partnership actually to help on the clinical development and commercialization. And what's in the future? Are you interested in building your in-house commercial structure outside of China? So, I guess we are open to all kind of option. I, I mean, our company has always been focused on, as I said in the beginning, bringing good quality products, not just to the China market, but to overseas market. Now, the China market, I think especially now that we have established very good manufacturing as well as, marketing team, we are very confident that we can do it, ourselves. But for the overseas market, I think is, we have to look at it case by case. You know, and I think the capital market condition may also be a factor that we have to consider. Do we, you know, invest in, you know, a big phase III registration trial overseas, or do we ask a partner to come in before that and help us to fund that? Now, this is always a balance, right? And the other thing we would continue to consider is that, at various stages of clinical development, we will, you know, explore different path or indication. Of course, some indication may be much more attractive to the overseas market than some less. So no straight answer to that one, you know, except the fact that we continue to aim for overseas revenue. But whether through our in-house sales staff or with partnering with multinational companies, we are open to all sorts of ideas. Now, the fruquintinib with Takeda is a very successful case that if we come across that again, a scenario like that, definitely we will go after this. But for some other indication, you know, we will also consider various different type of options. Yeah. Okay, terrific. We'll wrap up here, and thanks for a very great discussion. Thanks, everyone, for attending. Thank you.