HUTCHMED (China) - H1 2024

Transcript

David Ng (Head of Investor Relations)

Hello, everyone. Welcome to HUTCHMED 2024 Interim Results Presentation. My name is David Ng, Head of HUTCHMED IR. Our results announcement, as well as our presentation slides, have already been uploaded to our company homepage, as well as the Hong Kong Stock Exchange website. Before we start, just a few quick reminders. All audiences are currently muted during the presentation by our management, and then we will be followed by a Q&A session. Second, please type your name as well as your company name to show up on your screen. And finally, please read on page two of our presentation slides for the safe harbor statement and disclaimer. The performance and results and operations of the HUTCHMED contained within this presentation are historical in nature, and past performance is no guarantee of future results.

Without further delay, let me introduce our Chief Executive Officer and Chief Scientific Officer, Dr. Weiguo Su, to begin our presentation for today. Dr. Weiguo Su?

Weiguo Su (CEO)

Thanks, David. Good evening. Good morning, everyone. Welcome to HUTCHMED First Half 2024 Results Conference Call. With me today are Johnny Cheng, CFO, George Yuan, Head of Commercial. George joined us a month ago. George is a highly experienced veteran in oncology product sales and marketing. He joined us from Merck, where he headed its China commercial operations for the last 7 years with great success. George will be followed by Mike, who will give a brief update on the pipeline. Next slide, please. Slide number four. Just to give you a quick summary, first half 2024, we continue to execute on our strategy towards self-sustaining. As a big part of this strategy is globalization.

We are launching fruquintinib worldwide with our partner, Takeda, and we look forward to filing for approval for our second product, savolitinib, in the U.S. later this year with our partner, AstraZeneca. On the pipeline, we continue to file for life cycle indications for the first wave of products. At the same time, the second wave of products, sovleplenib, tazemetostat NDAs, are under review in China, and we expect to launch them in the next 6-12 months. Our best-in-class IDH1/2 inhibitor, HMPL-306, entered into phase III in recurrent and refractory AML. On commercialization, first, an update on FRUZAQLA US performance. H1, in-market sales reached just over $130 million, suggesting strong early uptake. We expect EU and Japan launches later this year. In China, all products experienced a double-digit growth while fighting through fierce competition.

Taken together, the combined market, the combined in-market sales grew 145%, primarily driven by FRUZAQLA US sales. So with that, I'll turn it to Johnny Cheng, CFO, to give you more details on the financials. Johnny?

Johnny Cheng (CFO)

Okay. Thank you, Dr. Su. So, on page six, as you all can see, we have made profits of $26 million in the H1, with revenue of marketed products up 64% at constant exchange rate to $128 million. So oncology consolidated revenue achieved at $168 million, on track to meet our full year revenue guidance of $300 million-$400 million. R&D expenditures have reduced to $95 million, mainly due to a strategic reorganization of the ex-China team and prioritization of projects. Turning to the next page, page seven. On the guidance, as highlighted just now, we are on track to meet our full year oncology and immunology revenue guidance of $300 million-$400 million.

So we are likely to achieve the high end of the guidance due to the potential additional commercial milestones from Takeda. In addition, we are also likely to receive EU and Japan related milestone in the H2. Moving on to the next page, page 8. On the balance sheet, as you can see, we continue to maintain a strong cash position of over $800 million. So on the bank borrowings, we are drawn from a low interest bearing facility for the construction of our new Shanghai factory. We are getting net positive income as our actual borrowing rate is lower than our interest rate earned on our short-term deposit. Now, I will pass to our Head of Commercial, George Yuan. George?

George Yuan (Head of Commercial)

Thanks, Johnny. Firstly, as Dr. Su mentioned, we have a very strong start of fruquintinib in U.S. This shows you the slide. 10 shows you the U.S. results. We see very strong Q1 and an even stronger Q2. And if you look at the future, we are expecting Japan approval in a very quick fashion, and also we are waiting for EU reimbursement position. Next slide. Look at the China market, fruquintinib in a very competitive market, we still deliver a double-digit growth, and we are still the market leader in the 3L mCRC, and we believe the mCRC still has a room to grow in China. Additionally, we receive a Hong Kong approval for mCRC 3L. Next, move to the next slides, for SULANDA.

This is, we have delivered, in the H1 of this year, we delivered a very good growth, and we are the number two brand in the NET treatment market, and also we are gaining market share. If you look at the guideline, we get a multiple endorsement for the treatment in CSCO, in CAP guidelines, and also we believe there's a lot of room to grow because this area is still underdiagnosed, and some of the treatment still need to be, for, to form the guideline. If you look at the next slides, ORPATHYS, our first-in-class MET inhibitor. We see the market become more crowded, but the growth of the H1 of this year is still strong, and the MET 14 testing become a standard of care in the market.

We still believe, with AstraZeneca's strong platform in lung cancer, we can deliver a much stronger growth in China. Looking forward, we are preparing our ITP market growth. If you look at this market, this is our first-in-class launch in China, and we are. This product paves the way for us to move into immunology field, and we will sequence our business priority to address the low-hanging fruits first, then going to a major market after an ideal application. Then, if you look at the company, we are preparing the market, we are preparing the products, and we are preparing the organization to prepare the launch. If you look at the overall China commercial environment, we believe, with current encouragement of China innovation, the market situation become more favorable for the innovative medicine. Now, let's introduce Mike, our CMO.

Mike Shi (CMO)

Thank you, George. Next slide. Yeah, our product pipeline are continue to grow and mature. As you can see, we're actually making a lot of progress. We have six NDA or supplementary NDA under review globally. Not only for fruquintinib, we have, you know, international approval based on the FRESCO-2 result. We also have the FRUTIGA and also the FRUSICA-1 for additional indication in gastric cancer, in the endometrial cancer. More importantly, we also have a new product is under review. We have the sovleplenib for the second-line ITP, and also a new product, tazemetostat, we licensed from Ipsen, also under priority review in China. And additionally, we have the savolitinib also for the confirmatory trial for MET-driven under review for first-line non-small cell lung cancer.

So our additional pipeline continues to grow. We are very excited later this year, our partner, AstraZeneca, based on the SAVANNAH trial, will have the potential to bring the savolitinib into the US NDA submission. And also in the next few years, we continue to advance our pipeline in the registration study. And Dr. Su mentioned about the RAPHAEL study, our new class compound, IDH1 and IDH2 inhibitor, HMPL-306, also initiated the phase three trial. Next slide. Slide 18, we have presented our second-line gastric cancer for fruquintinib in combination with paclitaxel at the ASCO Plenary early in February, and also had the updated results in at the ASCO plenary session. We are really pleased that the robust clinical data showing the double the overall objective response rate and also the progression-free survival.

And also, we look at the longest overall survival in the second-line setting has been reported, and this NDA is currently under the CDE review. Slide 19, please. And also, we update our FRUSICA trial, and fruquintinib with PD-1 sintilimab in the endometrial cancer. We reported the results at ASCO, and we have seen very robust overall response rate, 35.6%, overall response rate, and the median PFS, 9.5 months. So this NDA has been accepted under priority review at the CDE. Next slide. Also, our fruquintinib plus sintilimab in the RCC also fully recruited. We are waiting for the events for later this year. If positive, we're going to file additional NDA for fruquintinib in the RCC. Slide 21.

And also, we are very excited about our next new product, our first innovative molecule, the Syk inhibitor. We reported results of our ESLIM-01 phase 3 at the EHA, and also with the simultaneous publication in Lancet Hematology. And it really shows this compound has a very robust best-in-class molecule in heavily pretreated patients. Over 75% of the patients pretreated with TPO, TPO-RA, also show a very robust durable response rate, 48%, and overall response rate, 71%. And the this platelet increase is very rapid within after a week. And also the side effect profile is very favorable compared with the low off-target effect, and there's no thrombotic event like TPO-RA has.

And also internationally, we started the phase 1 trial in ITP in US, EU, and Australia. And also at the EHA, we present our clinical proof of concept trial for warm autoimmune hemolytic anemia, and also selected prime plenary presentation, also show very robust 48% durable response rate and overall response rate of 67%. So the phase 3 trial is already started enrolling patients. And for international development, we really think this is a great molecule, has a best-in-class potential and multiple development opportunity for example, in second-line ITP, in TPO-RA pretreated patient, and also you know, there are other opportunity in combination with standard of care and also potentially secondary ITP or other autoimmune disease. Slide 22. We also excited to see the advancement for savolitinib, our MET inhibitor.

We have approval in China and also our global partner, AstraZeneca, has completed the re-enrollment and with the readout in the second and third line Tagrisso combination trial in MET-aberrated patients. So the results we're reading eagerly, with the potential for our second international NDA later this year. And also in China, we already submitted the MET exon 14 in the first line, and also the, as a confirmatory trial for approval in MET exon 14 skipping mutated patients. And also the, our second line, EGFR, for refractory patient with MET amplification, the SACHI study, we're aiming to complete the trial enrollment later this year. And in addition, our partner and continue to enroll in the other four phase III trials ongoing, two led by AstraZeneca and two in China. Next slide.

Also, at the R&D day, we update the outside world about we are launching this phase 2/3 trial for surufatinib in combination with chemo in first-line pancreatic cancer. This is really based on the high unmet need and also the robust clinical data we have seen from IIT trial in surufatinib plus camrelizumab, the PD-1 inhibitor, with S-1 and ABRAXANE versus the standard of care. We can see the overall response rate of reaching 50% versus 27%, median PFS 9 months versus 5.8 months, and also the long overall survival of 13 months. So this is really exciting data. We really continue to enroll in this phase 2/3 trial and further advancing our pipeline in this first-line PDAC. Slide 24.

Also, I mentioned that RAPHAEL trial has started enrolling patient. This is our first dual inhibitor, IDH1 and 2 mutated, double mutant, inhibitor, and it's addressing a high proportion of AML patient and with high unmet need. We have reported our data, both the China AML trial and also the international trial. We have seen very robust, CR response. Next slide. As you can see, we reported at the RP2D dose, which is the 250 mg loading dose, followed by a 100 mg dose. We have observed very robust, CR and the CRH rate in the IDH1, mutated patient.

You can see we reach 50%, and in the IDH2 mutated patients, see 62.5%, which is really robust result if you're excluding the co-driver mutation with FLT3, KRAS. And also, very importantly, we observed very long overall survival, and we have seen the 13 month overall survival in this IDH1, IDH2 mutated patient. So really showing this compound has a best-in-class potential in inhibiting both IDH1 and IDH2. So the phase three RAPHAEL trial is currently ongoing and enrolling patients. We are very, very excited about this compound. Next, I'll turn back to Dr. Su.

Weiguo Su (CEO)

Okay, thanks, Mike. To sum it up, you know, we had a strong H1, and-

Mike Shi (CMO)

Yeah, we did.

Weiguo Su (CEO)

-and we are optimistic about the H2. Our previous target was to achieve profitability by end of 2025. We believe we are well on our way and potentially ahead of the curve. Looking ahead, there are a lot of events on this map, all lined up for 2025, 2026, and beyond. These events, if achieved, will help fuel the growth for years to come. This concludes the presentation, and thank you again for attending the call. Next is gonna be Q&A.

David Ng (Head of Investor Relations)

Thank you, Dr. Su. Thank you, everyone, for presentation. Next, we will have the Q&A session. There are two ways that you can ask the question. You can type your question in the Q&A box by just pressing the Q&A button at the bottom of your screen, or you can raise your hand, and after we call your name, we will unmute your line, and then we can, you can ask your question directly. So, let's first start with the very first question. It will be Alec Stranahan from Bank of America. So, Alec, your line is now unmuted. Please ask your question.

Alec Stranahan (Biotechnology Equity Research Analyst)

Okay, great. Thanks, guys, for the questions, and congrats on the progress in the H1. Great to see the FRUZAQLA launch, and also hitting on all cylinders in the U.S. Two questions on SAVANNAH. First, you know, how do you see the data earlier this year at ASCO for Savo as potentially reading into what we could see in the full data readout from SAVANNAH later this year? And then, who would be leading the U.S. submission for Savo, and is the year-end timing sort of from you guys or from AstraZeneca or both? Thank you.

Weiguo Su (CEO)

Okay. Thanks, Alec, for the question. So briefly, obviously, AstraZeneca is leading the trial, and, but for NDA submission, it will be a complete package, including preclinical early development. So we will be contributing to the package, but operationally, AstraZeneca is leading the whole thing. In terms of data, I'll ask Mike to comment.

Mike Shi (CMO)

Yeah. So we have report our data previously, right? The WCLC and, you know, particularly in MET-driven population, we do see a, you know, good MET-amplified patient, you know, with, 50% ORR and, over 7 months PFS. So certainly, we are quite excited about this, molecule and the clinical data, and so we'll expect the readout, of course, from AstraZeneca, right? Once, once the data is mature enough later this year. If this is positive or repeat for previous study, previous result is certainly, you know, per the agreement with FDA, this will be the NDA submission package as AstraZeneca is gonna, you know, submit. Yeah.

Alec Stranahan (Biotechnology Equity Research Analyst)

Great. Thanks. And maybe one quick one, if I can, just on FRUZAQLA. Given you guys are manufacturing for Takeda, what kind of inventory stocking dynamic do you expect is going on, and what kind of inventory levels are you guys shooting for? Thank you.

Weiguo Su (CEO)

So you know, we are obviously helping Takeda on the manufacturing. I think they are catching up on the inventory. In the early going, it was pretty thin. I think now pretty much caught up. At the same time, now we are preparing for the European launch and also Japan launch as well. So, we're basically doing full-time manufacturing for Takeda to support the preparation for launches.

Alec Stranahan (Biotechnology Equity Research Analyst)

Got it. Thank you, and congrats again on the progress.

Weiguo Su (CEO)

Thank you.

David Ng (Head of Investor Relations)

Thank you, Alec. So, our next question is from Chen Chen of UBS. Chen Chen, your line is now unmuted. Please ask your question.

Chen Chen (Equity Research Analyst)

Thank you, management, for taking my questions. So my first question is on fruquintinib. Well, it has very strong sales momentum in the US, so any chance for us to raise the sales guidance? And also, can management please elaborate a bit more on its like EU sales strategy? And can you please also like update on the regulatory approval status, like in China, in second line gastric cancer? Yeah, that's my first question. And my second question is on sovleplenib. I want to know like is China commercial strategy, and what is our sales guidance for the first year of commercialization? And also any like BD progress. And it would be good if we could also elaborate a bit more like is US and EU clinical trial plan. Thank you very much.

Weiguo Su (CEO)

Okay. Thank you very much for the question. You know, while we are happy with the early performance of fruquintinib in the U.S., we, I mean, Takeda doesn't have any, at the moment, doesn't have any updated or any update on the forecast or guidance. So, we'll let you know as well we hear from Takeda on that. Regarding Europe, obviously, you know, it was approved in late June, and we've been supporting Takeda in preparation for launch there, and it's gonna be country by country. Obviously, you know, pricing, negotiation, reimbursement, payer is obviously very complicated. So, but we do expect, you know, potential launch before end of this year in Europe.

I think Japan will. At the moment, the re-NDA review is on track as well. Sovleplenib, obviously, BD discussions are ongoing. We continue to engage with potential partners. At the same time, we just focus on clinical development globally or outside China. As Mike mentioned, the dose optimization of study kicked off early this year. We have multiple centers in the U.S. and in Europe now open, and we are just screening patients and enrolling patients at the moment.

I would expect that the business development discussions will continue, along with clinical development as we progress through those optimization and towards potential registration or kickoff of the registration study. I think that's about clinical development. In terms of, you know, China commercialization or China launch or preparation for China launch, a lot of work is going on at the moment. As George already, you know, pointed out, we are still working on the marketing strategy, and also preparing the organization as well. You know, so work is ongoing. At the moment, we don't have any forecast for next year.

I think we'll have to work through the models, and I think a major piece of it will be pricing. At the moment, we are not ready to make any decisions on that yet. So, you know, when we are ready to share, we'll share with you, with everybody, our forecast going forward. So really nothing to share at the moment, other than to say we are working very hard to prepare for the launch.

Chen Chen (Equity Research Analyst)

Yeah.

Weiguo Su (CEO)

Thank you.

Chen Chen (Equity Research Analyst)

Thanks for the information provided. Can you also please let us know the regulatory approval status of fruquintinib, like in second-line gastric cancer? Can we expect, like, anything in August or September?

Weiguo Su (CEO)

So all we can say is the NDA review is still ongoing, and we, you know, we don't comment. We actually can't comment on the regulatory processes. But maybe, Mike, if you have anything to add, please chime in.

Mike Shi (CMO)

Yeah. I think like Dr. Su said, right, the regulatory is ongoing. We cannot comment now, and although we have prepared, I mean, the, you know, updates, right, for additional analysis to CDE, but, you know, we anticipate the decision will be Q3 this year. Yeah.

Chen Chen (Equity Research Analyst)

Okay, cool. That's very clear. Thank you.

Mike Shi (CMO)

Thank you.

David Ng (Head of Investor Relations)

Thank you, Chen Chen. Thank you, Dr. Su. Thank you, Mike. Just a reminder for anyone who may want to type in the question, you can type the Q&A box and put in your question there. Next question is from Jefferies, Clara Dong. Clara, your line is now unmuted. Please ask your question.

Clara Dong (Biotechnology Equity Research Analyst)

Hi, good morning. This is Clara for Kelly. Thanks for taking our question, and congratulations on all the progress. So just one quick question on fruquintinib. After around 10 months of launch in the U.S., obviously, we've seen really good launch momentum. Wondering, have you seen any dynamic of fruquintinib being used in earlier lines in colorectal cancer? And wondering, have you and your partner, Takeda, discussed any opportunity for fruquintinib beyond geographic expansion? And like, what's the appetite like for potential further development? Thank you.

Weiguo Su (CEO)

Okay. Yeah, thanks, Clara, for the question. Obviously, you know, U.S. launch is still young and very early, very early into the launch. We don't have any information. Actually, Takeda has not shared with us any information regarding usage in early lines. With regard to clinical development or, you know, maybe Mike can share more about, you know, data generated in China in earlier lines, second line, first line, as well as maintenance setting. And, you know, I think there are a lot of strong data there, and we'll continue to discuss with Takeda how we position in this particular disease segment. Mike?

Mike Shi (CMO)

Yes. So we have done, you know, quite some IIT study in the earlier line setting. First, I think, reported both at the ESMO last year and also ASCO GI and the ASCO this year, right? Their first-line maintenance setting combined with capecitabine, we actually see very good tolerability and the long PFS-1 and PFS-2 that was reported. And also in the second line setting, there are also multiple IITs really working on the combination with standard of care, including FOLFIRI. And also that was reported have a pretty good overall response rate and the PFS. So is certainly the safety for combo is really well. That's really reflect the fruquintinib as a highly specific VEGFR inhibitor and combined with a lot of other therapies, right? PD-1, chemo or so.

And also we see a combination with PD-1, also see quite good the survival data. So we're providing all this information to Takeda, and certainly the Takeda team is well aware of and you know, positioning their development down the road. Yeah.

Weiguo Su (CEO)

Thanks, Mike.

Clara Dong (Biotechnology Equity Research Analyst)

Very helpful. Thank you.

David Ng (Head of Investor Relations)

Thank you, Clara. Thank you, Mike. Thank you, Dr. Su. Our next question on the line will be Cavendish, Mr. Adam McCarter. Adam, your line is now unmuted. Please ask your question.

Adam McCarter (Research Associate Director)

Thanks, David. Thanks, thanks, everyone. A great, great presentation, and obviously, congratulations on the result. Great, great to see the news on FRUZAQLA and the momentum it's gaining in the U.S. I guess just my, my first question really is, again, just on fruquintinib and the story that's evolving there in gastric cancer. So obviously, you know, asking not asking the management team to predict the outcome, but I don't know if you could sort of give us an indication of how, how confident sort of you, you are in the strength of the data package that's been submitted to the Chinese regulators. And then just a sort of a second question, just on looking at the costs going forward into the second half of the year.

Obviously, we saw the first period, so quite a reduction in the R&D expenses, but just wanted to see, understand sort of how to think about that going forward, obviously, with the initiation of the ESLIM-02 and the RAPHAEL phase III studies, into the H2 of the year. Thank you very much.

Weiguo Su (CEO)

Okay. Thanks, Adam, for the questions. Maybe I'll ask Mike to comment on fruquintinib GC and also the RAPHAEL study, and Johnny can comment on expected cost in H2. Mike, go first.

Mike Shi (CMO)

I think, you know, we did mention earlier, right? This, you know, the clinical data was presented at ASCO Plenary and ASCO, right? The data was quite strong. If you can see the, you know, response rate, the PFS really double. And, you know, this study was, it was designed with PFS and OS dual primary endpoint. I just want to emphasize, right, if one of the endpoint is positive, it's considered as a positive trial. And, you know, the OS, in particular, it does not reach the statistical significance, but we did observe this is the reported OS is actually quite long, you know, compared with the in the second line setting.

One of the reasons it did not reach statistical significance is really we have reported during the ASCO Plenary and also the publication, published in Nature Medicine. There's an imbalance of the post-treatment, right? And there's a significant higher percentage of patients in the placebo arm, almost 20% higher received the post-treatment therapy. And so this is one of the reasons it did not reach statistical significance, but highly, we believe this is clinically relevant numerical increase of OS, and it's somehow confounded by the post-trial post-therapy treatment. Okay, so again, the data was submitted, and I also mentioned additional analysis, whatever we reported the CDE, but I cannot comment, right, about the approval. So I think the decision will come most likely by Q3. Yeah.

Johnny Cheng (CFO)

Okay, so on the R&D expenditure, first half, as you can see, we spent about $95 million. Certainly, I think, we haven't given any guidance to the market in terms of, the total full year R&D expenditure. But, you can expect, in because of, the phasing, one should expect that we will continue to invest, in our R&D program. So H2 you can expect, we will ramp up more R&D investment. Certainly it will be more than our H1. So full year, I think is still within the range that, we have, basically given some, indication earlier, that, we will continue to invest in a similar level of, of, last year. But certainly this year overall, I think will be, will be less than last year, slightly. Yeah.

Adam McCarter (Research Associate Director)

Excellent. Thank you. Thank you everyone, and, congratulations again, the results.

David Ng (Head of Investor Relations)

Thank you, Adam. Our next question is Paul Choi from Goldman Sachs. Paul, your line is now unmuted. Please ask your question.

Paul Choi (Biotechnology Analyst)

Hi, can you hear me?

David Ng (Head of Investor Relations)

Yes.

Paul Choi (Biotechnology Analyst)

Okay, great. Thank you for taking the questions. Good evening. My first question is just with regard to tazemetostat, TAZVERIK in China. Can you comment first on your appetite to explore it in additional indications beyond follicular lymphoma, you know, particularly either post-BTK or post-BCL? It seems like there's logic to target opportunities like double hit lymphoma and other lymphomas. And then second, in terms of the cadence of development for sovleplenib, I know you've obviously targeted ITP first here and additional indications, but just can you maybe also comment on what the cadence of what we should expect next in terms of development might be? Thank you.

Weiguo Su (CEO)

Okay, Mike, why don't you take a first, first.

Mike Shi (CMO)

Mm-hm.

Weiguo Su (CEO)

comment on this?

Mike Shi (CMO)

Yeah. Yeah, thank you, Paul. You know, I think, you know, tazemetostat, right, is certainly is the first-in-class EZH2 inhibitor. And to follow your question, not only in our filing is the third line follicular lymphoma. It was based on the bridging study for the global study. And, and we're also currently doing a second line follicular lymphoma, along with our partner, Ipsen. This is a global phase III trial. In the second line, FL, we are, we are working together with Ipsen on the enrolling the phase III trial, is the tazemetostat combined with R2 versus R2. So this is certainly is a big indication to expand the indication.

And also, currently we are, you know, at least for mechanistically, we are evaluating other opportunity for this indication. We have some combination study, you know, exploring the, the PI3K combination with tazemetostat. And, certainly Ipsen has done quite some exploratory study before, so we're working with Ipsen to address any of the new indication development. Yeah. And, Sovleplenib internationally, right? Because, I certainly we see the ITP, you know, the durable response rate, 48% is really robust compared with any of these, you know, ITP treatment, because, this, mechanism, we believe it is actually quite a unique, it blocking the, you know, the macrophage phagocytosis through the Syk inhibition, and also, working on the B-cell to pro, to reduce the autoantibody production.

So certainly this is a dual mechanism, really, explain this, the superiority compared with other molecule. And also, particularly, we are excited about these patients are over 75% actually treated with the TPO-RA. Average prior line therapy is four line. So certainly, ITP is our first indication, but we believe this, this goes far beyond that. And, wAIHA, also currently we're doing this trial in China, and this is certainly is a high unmet need because there's just no standard therapy, second line therapy globally, nothing. Yeah. And, so this is certainly a great indication to continue the development for the registration path. And also we're working, we think the Syk pathway is has a lot of opportunity, autoimmune disease, rheumatoid arthritis, with all the other indication.

So we think, certainly we are working on, you know, additional possible pop trial to further explore the opportunity for sovleplenib.

Weiguo Su (CEO)

Thanks, Mike. I just want to add, Paul, regarding tazemetostat, you know, yes, we have at the moment, follicular and epithelial sarcoma, but, there have been quite some progress in clinics in solid tumors, including Pfizer's recent report on CRPC. So internally, we are looking at these various potential solid tumors, obviously, biomarker driven, in addition to CRPC, potentially ovarian, small cell lung cancer, and so forth. So this, you know, I think it would be even more exciting than the third line follicular, where, you know, it's been obviously, it's getting quite crowded there. But still, tazemetostat has great safety profile, can be combined with many other therapies.

You know, in the second-line setting, in combination with R2, for instance, well-tolerated, and in the dose optimization study and also the early proof of concept, you know, great data there as well. So, you know, we think, it's got, you know, great potential.

David Ng (Head of Investor Relations)

Thank you, Dr. Su. Thank you, Mike. Paul, does that answer your questions? Okay. So, just a reminder, for anyone with questions, please, type in the Q&A box or raise your hand. The next question comes from Yang Zheng from Shanghai Pudong Development Bank. Yang Zheng, your line is now unmuted. You can go ahead and ask your question.

Yang Zheng (Analyst)

Thanks, management, for taking my question. Congratulations on the strong results. I've got two quick questions. The first one is on fruquintinib. We have seen the strong U.S. sales, and I'm wondering if you can have shared with us the doctors' feedback on fruquintinib. So in terms of the patients' constitutions, have we seen more patient, who are relapsed from the LONSURF or the new third-line CRC patients who never used LONSURF before? And, regarding to the quarterly sales trajectory of fruquintinib, considering we have, Europe approval already, and also Japan imminent approval, how do we think about the quarterly sales trajectory? For the full year overseas sales of fruquintinib, what are our current, sales guidance for the overseas of fruquintinib?

The second question is about our bottom line, because we are surprised to see that company has achieved the net income in the H1. In the opening remark, I believe we mentioned that HUTCHMED might achieve break-even ahead of our guidance year, 2025. So does that mean we will achieve break-even in 2024 and turn profitable afterwards? These are my two questions. Thanks, management.

Weiguo Su (CEO)

Okay. Okay, thanks. Thanks for your question. So with regard to, you know, patient mix in the US, we have no clarity at the moment, or we, at least Takeda hasn't shared with us. But, you know, during the FRESCO-2 study, obviously, the study population was patients already failed LONSURF or STIVARGA. So, I mean, still clearly demonstrated clinical benefit for those patients. So obviously, you know, in the U.S., we worked with the U.S. FDA to use the China study, FRESCO, and also the global study, FRESCO-2, to support third-line approval. Now, clearly, fruquintinib has a very unique pharmacological profile. Even patients failed on STIVARGA can still benefit from the fruquintinib treatment.

Although we don't have any clarity as to how many patients treated you know so far in the U.S. are fourth line, and how many are third line, at the moment, we don't have the information. With regard to full year guidance, as I mentioned, alluded to earlier, Takeda has not shared with us, any you know, their updated version of the guidance. So we don't have anything to share. I think if you looked at Takeda's report, their quarterly report just came out today, they said they expect, their oncology sales as a whole, I guess majority would be the vast majority would be fruquintinib. They expect, you know, more than 100% growth this year, this year.

So, you know, we don't have any more specific, you know, guidance to share at the moment. The bottom line, $25 million profit. It was a lot of effort internally from cost savings to maximizing the commercial values for our compounds. As again, as I pointed out early on, that our previous target was end of 2025 to break even or to reach profitability. I think we are well on our way. I think we probably will achieve that ahead of end of 2025, so for sure. Thanks.

Yang Zheng (Analyst)

Great. Great, thanks. Thanks, Dr. Su. Yeah, thank you. I have no more questions. Thank you.

David Ng (Head of Investor Relations)

Okay, Yang Zheng. So our next question is from Julie Simmonds of Panmure Liberum. Julie, your line is now unmuted. Please ask your question.

Julie Simmonds (Equity Analyst of Healthcare)

Thank you very much. I was just wondering, with the reduction in R&D expenditure in the first half of the year and sort of maybe, a slight reorganization of the focus away from ex-China trials, does that affect any of your earlier stage programs? Because clearly, we've got quite good visibility into what in the later stage ones, but does it change the balance of where the spending is going?

Weiguo Su (CEO)

Okay, thanks, Julie, for the question. I think the, you know, obviously we do routine portfolio prioritization, but, you know, any program worth investing, you know, we are fully support. I don't think we are terminating all the early programs. You know, so if anything, the portfolio prioritization is largely driven by data and by prospects, so really not so much about purely cost savings at all. If anything, as you know, we just initiated the phase I study on our MET inhibitor, which we think is a great compound, has best-in-class potential, in the class, and we are building actually an AML strategy.

So, you know, our decision on the portfolio prioritization is largely data-driven and also driven by our portfolio. You know, as we always communicate it, we are more of a pipeline company instead of just targets. We don't necessarily chase the hot targets. Instead, we look at our pipeline, look at what we have, you know, what additional targets or compounds we need to better cover the tumor types and address clinical needs. So that said, basically, you know, the short answer is that, and, you know, the, it shouldn't have, you know, we may delay a few specific programs that we think the data wouldn't support or the data is not clear, but by and large, we continue to invest in China. Great. Thank you.

David Ng (Head of Investor Relations)

Thank you, Julie. Just a reminder, if anyone still want to ask question, please raise your hand. So Dr. Su, I have one quick question on the Q&A box. Maybe I'll just read it out. So the question is, regarding our cash balance, that, you know, we have been quite well positioned and, you know, going to be profitable. Has the board considered how to use this surplus capital? Would it be, and how would it be deployed to further business development or will be returned to shareholders? Dr. Su?

Weiguo Su (CEO)

You know, I mean, we do have a very strong cash position with over $800 million in cash at the moment. However, we, you know, we anticipate gradually increase our investments in programs, in R&D, and also in our commercial organization as well, to better cover immunology section, for instance. So I think, you know, it's just a more of a capital management, if you will. So we clearly will continue to invest heavily in R&D, preparing for, you know, the future. We, I talked about the path to profitability and beyond, and all the way beyond, you know, 2027, 2028, but we have a lot coming. Very exciting programs from our discovery. I anticipate, you know, certainly the investment in R&D will gradually increase over the next few years. We do have a lot coming, very exciting stuff, in discovery.

David Ng (Head of Investor Relations)

Thank you, Dr. Su. Another question on the line is regarding our European launch. Of course, this will be depending on our partner. So the question is, while we await the individual country reimbursement decision, will there be any possible sales happening before the reimbursement decision has been made? Does it mean that we have to wait till much later this year or maybe next year before the sales can happen from Europe?

Weiguo Su (CEO)

I mean, it goes country by country, I guess. I think Takeda is working simultaneously with all these EU countries. Some in some countries, the process is shorter in other countries it can take longer. But, you know, you need to gain country-level approval before you can launch in these countries. At the moment, EU recommended, but we're or approved, but still need to work at a country level. They are working very hard and, you know, these launches will come and will start later this year.

David Ng (Head of Investor Relations)

Thank you, Dr. Su. We don't have any more questions on the line. Dr. Su, would you like to make some concluding remarks?

Weiguo Su (CEO)

Sure. Just, you know, I want to thank everyone again for attending the call. Clearly, as you can see, we are executing well on our strategy towards profitability. We made huge progress, and we had a very strong first half of this year, and we expect the momentum to continue. Again, thank you very much for attending the call.

David Ng (Head of Investor Relations)

With that, it conclude our 2024 interim result presentation, and if you have any further questions, please feel free to email us and talk to our IR team. Thank you very much, everyone.