Hutchison China MediTech Limited Sponsored ADR Aktie

Hello, everyone. Welcome to HUTCHMED 2025 Full Year Results and Business Update. Today, we're going to go through our results in a formal presentation by our senior management, and then it will be followed by Q&A. Before I start, let's turn to Page 2 with our usual safe harbor statement. Basically, the performance and results of our operation contained within this presentation are historical in nature, and the past performance is no guarantee of future results. The information in this presentation is subject to changes and HUTCHMED has no liability for any loss arising from the use of this content. My name is David. I'm the Head of IR of HUTCHMED. We are very happy that we're going to have our senior management to present the results. Let me hand off the time to our acting Chief Executive Officer and Chief Financial Officer, Johnny Cheng. Johnny?

Thank you, David, and thank you, everyone, for attending HUTCHMED's 2025 results webcast. Joining me today is our Deputy CFO, Lorenso Chiu, who will give us an overview of our financial performance. Our Head of Commercial, George Yuan, who will share with you our commercial performance; and our Head of Discovery, Dr. Guangxiu Dai, who will provide an update on our R&D pipeline progress. Next slide, please. A quick highlight of our 2025 achievements. We are pleased with our ex-China FRUZAQLA sales, which had 26% growth versus last year, resulting in $366 million in in-market sales. More importantly, FRUZAQLA has rolled out to over 38 countries already. As for our China sales, it has rebounded in the second half of the year, achieving 21% in-market sales growth versus our first half interim results.

In terms of our cash position, we have about $1.4 billion, which allows us to accelerate our global ATTC development and provide resources to explore potential in-licensing and M&A opportunities. On the right-hand side, we have now advanced 2 of our ATTC programs into the clinic, which we believe will have huge market potential. In addition, we are pursuing potential business development opportunities with multinational companies. In terms of the progress of our pipeline, I will leave it to Dr. Dai to share with you later on. I will now turn it over to Lorenso for the financial review and outlook. Lorenso?

Yes. Thanks, Johnny. And let me give an overview of our key financial highlights for 2025. Total oncology revenue was $286 million. This includes $71 million R&D-related upfront and milestone revenues. For oncology products revenue, as Johnny already mentioned, there was a rebound from our China oncology products, which recorded 21% growth in in-market sales in the second half, while FRUZAQLA continues its global expansion. On net income, we recorded a profit of $457 million for 2025, mainly due to the SHPL divestment gain of $416 million. Excluding this onetime gain, our core operations remain profitable.

Next, please. Our R&D expenses for 2025 was 148 million. Expenses were lower versus 2024 as many of our late-stage trials are in the completion stage with multiple NDAs now awaiting approvals. In addition, we began shifting our investments into our early-stage ATTC assets with 2 candidates already in the clinic. Our cash position has been further strengthened to about $1.4 billion. That positions us well to accelerate both investments and developments of our ATTC programs. Next, looking forward to 2026, our oncology revenue guidance is in the range of $330 million to $450 million. This reflects a solid growth from 2025, driven by strong growth in our China commercial products with contributions from new indications as well as FRUZAQLA continued scope expansions. In addition, let's consider the potential partnership opportunities for our new drug candidates, including ATTC. Now I'd like to hand over to George to give an overview of the China commercial.

Thanks, Lorenso. First, let's look at the FRUZAQLA, our business partner, Takeda's performance. They delivered a very strong 2025 with 26% growth, and if you look at the Q2 -- the second half, the second half, the growth actually is accelerated mainly due to the market expansion we launched some of the new markets like Portugal, Belgium and South Korea. Also, the strong Japanese performance and some of the Europe performance uptake also contribute a second half strong growth. This reflects a market needs for safe and effective medicine in the later-line mCRC treatment. Also the physicians experience enhancement and also the reimbursement progress contributed to those growth. If you look at the U.S., we do see some of the headwind, mainly due to the medical Part D redesign.

Next slide. For China performance under the brand name ELUNATE -- in China, we posted a minus 13% growth, mainly due to a soft performance in the first half as we scale back some of the sales force after our GC second line setback and also some of the productivity improvement programs. But we successfully turned around the business with more efficient approach to focus on the top-tier cities and hospitals. In second half, we delivered 33% growth and successfully renewed our online deal with no price cut and include our EMC second line. Also, we submit NDA for RCC, those are all contribute to our future growth.

Next slide. If you look at the ORPATHYS and SULANDA, which is 11% of our total 2025 in-market sales, they are relatively soft due to the fierce competition. For SULANDA, we also face multiple PRRT those nuclear medicine moving to the clinical stage and fighting with us with limited patient pool. Although we have some kind of headwinds, we do see some progress. First is for ORPATHYS, we have a first-line METex skipping, adding to the NRDL. Also, we have SACHI approval to drive future growth. Our SAFFRON/SANOVO readout what we are expecting in this year. For SULANDA, we maintain our market leader position in NET performance in the TKI markets. Also, we have renewed our NRDL with no price cut. Our Phase III PDAC study is on track.

Next slide. We are building on behalf -- in addition to our solid tumor, we are building our hematology portfolio. We get our first medicine, first-in-class treatment for EZH2 mutation and follicular lymphoma approved. This is our first hematology products launched in China. This also gives us a beachhead in the hematology, and also the TAZVERIK include our China's first commercial insurance drug list. We are one of the 19th medicine including drug list. This gives us a kind of future growth opportunity to explore the commercial insurance.

On the other side, those TAZVERIK provide us a beachhead in the hematology to leverage these products, we can engage our hematology opinion leaders, establish our core team with expertise in the hematology to prepare the future hematology launch. [Sovleplenib] prepared to launch early 2027, and our ITP is already resubmit and wAIHA indicating will potentially submit in the first half of 2026. Also, we have additional pipeline in the hematology, the IDH1 and 2 inhibitor for AML and also the BTK in the DLBCL also start our Phase III study. So in long run, we were aiming to build our very strong hematology portfolio. Now let's turn over to our Dr. Dai.

Thank you, George. I'll provide an update on our R&D pipeline progress. The 2025 proved to be a great year for our pipeline, featured by fast regulatory movement and high-impact clinical data. We have achieved major progresses across our core areas, oncology, hematology and our next-generation technology platforms. In oncology, savolitinib has reached critical regulatory and clinical milestones in both China and global markets. SACHI was approved in China in a speed record for second-line EGFR mutant, MET-amplified non-small cell lung cancer. SANOVO and SAFFRON completed Phase III enrollment and third-line gastric cancer filed NDA in China in late December 2025.

In hematology, savolitinib, our Syk inhibitor has solidified its position with ITP NDA resubmission and robust positive Phase III data readout in wAIHA. Perhaps most excitingly, our antibody target therapy conjugate ATTC platform is now a clinical reality with our lead assets, A251 and 580 moving into global clinical development. A251 has started patient enrollment in China and in the U.S., closely followed by our second ATTC drug candidate, 580, which was first dosed in patients just yesterday. Beyond this, we are seeing broad success with Fruquintinib EMC included in NRDL, Fruquintinib RCC and Fanregratinib, IHCC gaining NDA acceptance and Surufatinib moving into Phase III for first-line PDAC.

Next, I'll dive deep into how this progress is define our growth trajectory. Next slide, please. With savolitinib, we have dual focuses here, maintaining leadership in China and expanding the global footprint. In non-small cell lung cancer savolitinib has been approved in China for first- and second-line METex14 alteration as a single agent. For second line, the combination of savolitinib and osimertinib represents a promising chemo-free oral treatment strategy to address mechanisms of resistance due to MET alteration following EGFR TKI treatment in this advancing setting.

In this setting, SACHI has been approved in China and SAFFRON is expected to have a readout in mid-2026. For first-line SANOVO Phase III study of savolitinib and osimertinib will read out in the first half -- in the second half of 2026 or early 2027. Savolitinib is more than just a lung cancer drug. We also reached an important milestone in gastric cancer with China NDA for third-line MET-amplified gastric cancer being accepted and priority review granted.

Next, please. The data from SACHI is compelling. In 2026 Lancet publication, SACHI study demonstrated a clinically meaningful OS benefit, 22.9 months versus 7.9 months in ITT patients who didn't receive subsequent MET inhibitor treatment. The hazard ratio of 0.32 is a clear indicator of OS benefit. Earlier, we have presented at ASCO that combination of savolitinib and osimertinib shows a clinically meaningful improvement in overall response rate and duration of response versus chemotherapy as second-line treatment. In particular, SACHI demonstrated clinically and statistically meaningful PFS improvement in ITT patients as well as in patients who failed third-generation EGFR TKI treatment.

Next slide, please. Turning to Sovleplenib, a Syk inhibitor. Our focus is on addressing the large unmet medical needs in immune-mediated hematological disorders. In ITP, we have resubmitted our NDA in China. NDA has been accepted and granted with the breakthrough therapy designation and priority review. The clinical profile of Sovleplenib is highly competitive in the 3-year follow-up study, the median duration of exposure is over 86 weeks. The cumulative durable response reaches over 66 weeks. Over 51% of patients achieved durable response. This is highly consistent with 48.4% durable response rate in the double-blind phase of ESLIM-01 study. Sovleplenib shows a superior durable response rate compared to many existing ITP therapies, including Syk inhibitor fostamatinib and BTK inhibitor, Rilzabrutinib as well as Efgartigimod and FcRn drug approved for ITP in Japan.

Sovleplenib's durable response rate is comparable to or better than TPO/TPO -RA drugs. A key differentiation for sovleplenib is its safety, particularly regarding vascular risks. It's well known that TPO/TPO -RA drugs have been associated with thromboembolic and thrombolic complications in ITP patients. Sovleplenib clearly demonstrates a highly competitive clinical profile in the safety and efficacy. Next slide, please. The ITP market potential is significant and growing. In China alone, there are over 250,000 actively treated ITP patients, representing an addressable market of USD 500 million to USD 700.

Next, please. Next is our innovation engine, the ATTC platform. This platform is designed to combine the precise delivery of antibodies with the potency of target inhibitors. A251 is a first-in-class ATTC consisting of a potent PI3K/PIKK inhibitor conjugated to an HER2 antibody with a DAR 4 through a cleavable linker. Next slide. A251 targets a massive global market across several HER2-expressing solid tumors, including breast cancer, gastric, gynecologic cancer and many other HER2-expressing cancer types. Next, please. The scientific and strategic importance of this platform targeting the PAM pathway cannot be overstated. The PAM pathway is the most frequently altered pathway in solid tumors appearing in 38% to 50% of all tumor cases, much higher than the other major drivers like RAS, HER2, EGFR and ALK.

For instance, PAM alterations are often seen in breast cancer, gastric, ovarian and cancers, prostate cancers. This gives A251 and other assets from this platform a massive total addressable market. Next slide. While small molecule inhibitors targeting PAM pathway and PIKK pathway have historically faced issues with high toxicities and poor [indiscernible] PK properties, it is always challenging to balance clinical efficacy and safety. The ATTC platform is designed to reduce these on-target off-tumor toxicities by delivering the payload directly to the tumors. The A251 payload is a potent inhibitor targeting multiple nodes in PAM pathway and PI3K pathway with high affinities in PI3K alpha, other PI3K isoforms and mTOR, ATR and ATM.

Its biochemical profile significantly differentiates from the profiles of the others targeting PAM and PIKK. We believe this is an advantage of the ATTC approach. The payload demonstrates high kinase specificity in a broad kinase panel hitting targets in the 2 families only. Next slide, A251 demonstrates strong HER2-dependent inhibitory activities, meaning IC50 is in the range of 0.2 nanomolar in HER2-positive cells regardless of PAM status in a single-digit nanomolar in HER2 low compared to 36 nanomolar in HER2 non cells. The HER2 expression level really determines how much of the payload is delivered to the tumor cells and how potent A251 can be. And crucially, A251 exhibits a bystander effect that allows it to overcome HER2 heterogeneity by killing neighboring HER2 non cells.

The preclinical data has been published at 2025 EORTC conference. Next slide, please. A251 has started a global Phase I study in the U.S. and in China. The dose escalation and building dose expansion and optimization is essentially one study in China and U.S. following the same protocol. We believe this is the fastest way to define a global dose. The trial targets HER2-expressing solid tumors with PAM status being tested retro respectively. This will inform the biomarker strategy for future development. The strategy includes utilizing A251 as a monotherapy for late-line treatment and exploring combination therapies in frontline setting. Next slide. We are accelerating discovery and development of ATTC and ADCs and this is the next-generation innovation time line. Our second ATTC asset 580 has started the Phase I opening sites and recruiting patients in China and in the U.S.

The third ATTC asset 830 is anticipated to enter global Phase I this year. We are committed to maintain the momentum from the innovative platform in the coming years. Next slide. Looking ahead next 15 months, the upcoming milestones include for savolitinib, we expect readouts for both SAFFRON and SANOVO. We anticipate the label expansion with China NDA approval for the third-line gastric cancer indication. For Sovleplenib, our Phase III trial in wAIHA successfully met its primary endpoint, clearing the path for the next regulatory filing, which will happen in the coming months. Our next major milestone will be the China NDA approval for ITP. For the innovation platform, 3 ATTCs will all be in the clinical development in 2026. Beyond these highlights today, we expect China NDA approvals for Fruquintinib, RCC and Fanregratinib in IHCC as well as Surufatinib PDAC enrollment completion within the next 15 months. We look forward to another great year. And with that, I'll turn back to our acting CEO, Johnny.

Thank you, Dr. Dai. So in summary, we are very excited about our outlook for 2026 and beyond. We have multiple potential NDA filings upcoming, so including from SAFFRON and SANOVO readouts later this year. In addition, our new hematology products are expected to drive future sales growth in China. On the innovation side, our strategic efforts will be focused on accelerating global development of our ATTC programs and at the same time, exploring business development opportunities to further validate and add value to this platform. Finally, our oncology revenue guidance of $330 million to $450 million factors in our FRUZAQLA ex-China commercial growth and the positive impact of adding new indications for Elunate. With that, I will turn it over to David to start our Q&A session.

Thank you, Johnny. Thank you, everyone, for the presentation. We will now do the Q&A session. [Operator Instructions] The first question comes from CLSA, Matthew.

Congrats on the results. I've got a few questions. First is regarding the oncology guidance in '26. In '25, you received multiple, for example, sales team restructuring kind of stuff, the growth is actually a decrease. So the '26 guidance seems to imply something 15% to 16% year-over-year oncology growth. So can you elaborate a little bit more about how I should be modeling the key drug sales for this, yes. This is my first question.

Asking my question in one batch. And second thing is about the kind SAFFRON readout. Do you have any color why the top line readout has been delayed from first half to second half? And third question is -- the last question is about -- can you elaborate more on the indication of the ATTC platform the first 2 candidates into the clinic, for example, the A251 [indiscernible]. And my understanding right that is more like on the post HER2 refractory breast cancer setting what kind of setting we are looking at in the future?

Thank you, Matthew. So for the first question, I will defer to Lorenso and the second and third question is to Dr. Dai. Lorenso?

Yes. About the guidance -- Matthew, thanks for the questions. About the guidance, as you pointed out, for 2025, there was a decline in the product sales. But as you can see, in the second half, we saw a strong momentum of recovery. And we expect that this will continue in the 2026. And together, we'd like to highlight, that we're expecting more growth coming from the new indications. As you can see, we have the [indiscernible] RCC, which is currently under review. And we believe that with that approval, that will bring in more revenue and the growth. And also about the FRUZAQLA, there's a strong growth in '26 expected due to the continued expansions of Takeda. And also, we can see that there are more and more countries are now in the market. And then with that full year penetration in 2026, that will continue the growth. Johnny, do you anything you want to add?

Okay. So second and third question, Guangxiu -- Dr. Dai.

Yes. So the SAFFRON readout is expected to happen in mid-2026. And the third question, A251 now is enrolling HER2 expressing solid tumor patients not restricted to post HER2 patients.

The next question comes from Matthew Guggenbiller. Go ahead, Matthew.

Can you hear me okay?

Yes.

Great. This is Matthew, on for Alec Stranahan from Bank of America. I guess 2 questions from us. On the SAFFRON readout, you said expected May 2026. Can you maybe clarify expected location of that medical meeting versus company event? And then for ATTC readouts, can you just maybe clarify expected patient number sort of follow-up we can expect from those?

Dr. Dai?

Okay. So the SAFFRON readout will be in, like I said, in the mid-2026. We'll share the data as soon as [indiscernible] informs us of the results. What's your second question? Can you repeat your question?

Yes. In terms of initial clinical data for the ATTC assets, sort of size and scope of those in terms of patient number follow-up?

The trial is still at early stage. We don't have a definitive time line for the data readout.

Got you. And then maybe one on commercial dynamics as well. I think first half had some headwinds from off-label sales, increased generic competition and sort of sales force turnover. I guess, can you speak to how those trends are looking in the second half and whether you expect those to stabilize throughout '26?

Okay. Matthew, we invite our Head of Commercial, George, to answer this question.

We -- because we cannot -- for the GC last year, we faced some GC setback. The indication is not yet approved. That's why if you look at the sales force, the original setting is we prepare for the GC. So the field force is a little bit overcapacity when we lost the GC indication. That's why we rationalized the team and also we try to focus more on the top hospitals. And that's why we have some kind of [indiscernible] the team, which lead to some kind of performance issue in the Q1 and the first half -- but everything is moving into the right direction. The turnover is significantly reduced. Also the vacancy is already filled. That's why we have a very strong team now, and those kind of momentum will carry over to the 2026.

No follow-up question, then David.

Next question is from Cavendish, Adam.

So a couple of questions. So yes, just in today's announcement, I noticed that you mentioned that AstraZeneca continues its efforts to increase MET testing as a standard of care in late-stage non-small cell lung cancer. And could you comment on how the pace of MET testing adoption might influence the potential uptake of savolitinib in the [indiscernible] setting in China and then globally, if SAFFRON is successful?

Yes. So Dr. Dai, yes.

We do not have additional information on this question.

Okay. No problem. Just on the second question then. So on the ATTC platform, could you elaborate on your partnering strategy, you are pursuing with the multinational pharmaceutical companies? And more specifically, are you considering out-licensing certain assets earlier in development to accelerate validation of the platform while potentially regaining greater control over other assets to maximize longer-term value?

Well, I think I will answer these question. In terms of our strategy for the partnering with the ATTC program, first of all, I think as you can see, we have a strong pipeline already building up for this ATTC platform. So we now have positive responses from potential partners, and many of which are multinational companies. We have ongoing discussion with all those potential partners.

So with our large portfolio that we anticipate that we will build on, I think we want to advance and accelerate this development. So hence, we have considered to potentially license out some of these programs. So also, in addition, I think we also have this AI capability, which we can further develop some more candidates into our platform. As a result, I think this is why we also consider potential partnering opportunities. Furthermore, I think as this platform is really one of our next wave, we would also like to validate this through this partnering strategy.

That's great. And I guess just if I could try my hand on final question is just sort of maybe a broader one. As we think about the HUTCHMED story going forward, how should investors balance the contribution of the existing commercial portfolio against the emerging opportunity from the ATTC platform? And in particular, do you see the next phase of value creation increasingly driven by the pipeline and the platform assets rather than the marketed product?

Well, we see, as we have our second wave of, as we mentioned, hematology asset that will be going into the commercial side that would add into our existing commercial -- already commercialized portfolio. So that would be increasing our balance of our investment in R&D. So we will continue to ramp up our R&D expenditure. Last year, in 2025, in terms of our investment in R&D was probably the lowest in recent years, mainly due to a lot of programs we're waiting for approval -- pending for approval, and we are also at the early stage of development of this ATTC program. But going forward, we do take this accelerate our global development strategy for ATTC. And at the same time, with the expanded commercial assets, we will be able to generate more income, so we can balance out our ATC investment.

The next question is coming from UBS, Chen Chen.

Well, my first question is on surufatinib. We see that it has started Phase III patient enrollment. So I'm interested in like partner strategy. So are you considering like BD like after data readout? Or you are now in talks with any potential partners right now because the Phase III will enroll like a few hundred people, so it would be very expensive.

Okay. I will answer from a strategic side, and then I will invite Dr. Dai to comment further. We have no -- at the moment, no intention to partner this program out. But Dr. Dai in terms of the status of our development, you can -- perhaps you can comment a little bit.

Sure, Johnny. So the Phase III first patient in has -- was achieved in December 2025, and we hope to finish the Phase III enrollment in the next 15 months. And we hope that surufatinib can provide another therapeutic option for the first-line PDAC patients and agree with Johnny that currently, we don't have our licensing.

I see. That's very clear. Well, so my second question is on your like R&D guidance in this year. So we noticed that you have started like a few Phase III trials such as like surufatinib as we discussed just now and also like BTK, DLBCL and also a few like early-stage trials such as ATTC candidates. So I'm just wondering like what's your guidance for your R&D expense this year?

Okay. Just to clarify, we do not give out any public guidance on R&D expenditure. But as we mentioned that 2025 was the lowest level. We do intend to ramp up, as you also mentioned, a number of programs that we are actually advancing as well as our strategy on accelerating our ATTC program. So going forward in the next few years, we do want to ramp up to a very reasonable kind of higher level of investment on R&D in the range of $250 million to $300 million, I think that would be the ideal level of R&D investment. Of course, we will be -- stick to our commitment to the investors that we will be profitable in a sustainable situation. So therefore, we will be investing as we will be able to generate sufficient commercial income to cover our R&D investment.

Okay. Great. Maybe the last question for me. So I saw that you have a very strong cash position by the end of 2025. And you also mentioned that you are planning to do some like in-license and also some M&A. So can you please elaborate a bit more on that side?

Yes. So yes, $1.4 billion of cash on hand. So our priority is, of course, as we mentioned, accelerating our global development for ATTC program. We are open because with these cash resources, we are open if the opportunity arise for in-licensing late-stage commercial assets or potentially some assets that is complementary to our portfolio. But I think M&A and this in-licensing opportunity, we are open-minded because we are in a good financial position, but we have no fixed target at this stage.

The next question comes from Panmure, Julie Simmonds.

I was just wondering on the move into hematology products, whether this changes what you're investing in sales and marketing and what changes to the sales infrastructure it requires.

Thank you, Julie. So George, would you like to comment on this?

Because hematology is a very specialized team, that's why we already start up a new business unit with dedicated sales, marketing and medical capability to address this kind of market opportunity. And with the future pipeline adding to the business, we will expand the team.

Lovely. And then secondly, just on the impact in the U.S. of the Medicare Part D changes. Just wondering how much impact you expect that to have on sales in 2026, whether you can make any comment?

Sorry, I didn't hear your question. Could you repeat again?

Yes. Just questioning about the changes to Medicare Part D that went on in the states that are obviously impacting your sales there. And if you've got any thoughts on what impact that might have into 2026?

We have received no new changes so far. The impact factors into 2025 has been reflected. Despite that impact for U.S., I mean, we still achieved a 26% growth for our food sector through our partners. So we do anticipate that in -- sorry, 2026, we will be expanding rolling out of all the ex U.S. countries. So far, already 38 countries have been commercialized in terms of this food sector. And we continue to see that the NRDL in those countries will be expanded. So the total impact for ex-China sales, we see that U.S. will continue to grow, but also outside of U.S., that is the key driver also.

Next question coming from Daiwa, Wilfred Yuen.

I want to follow up on the revenue guidance that range from $330 million to $450 million, which is a wide range versus last year anyway. Maybe can you give us more color as to the breakdown between the oncology product sales and the R&D milestones payment? Are you expecting some additional milestone maybe to hit the high end of the guidance $450 million?

Lorenso, would you like to tackle this question? I will add to it.

Yes. Further to what I explained earlier, I think you can look in this way because we do not give any guidance of particular items within this revenue guidance. But for your information, I think it will be worth to note that in 2025, our revenue has included some of the upfront and milestones, which if you exclude those, the base would be lower. And then for the 2026, the guidance reflect a kind of a solid growth from 2025. In addition, I think some of the factors that I mentioned, the growth from our China -- China products with the new label expansions and also the new indications would drive further growth. So I hope that could address the questions. Johnny, do you want to add some more comments on this?

So Wilfred, I think basically, you should take the guidance as the middle of this range, right? So the lower end potentially, if some of the -- at this, I think the low end of the guidance is where we are very confident, and we are also very confident that to achieve high of this guidance. So $330 million has factored in, as Lorenso said, many of the organic growth.

In addition, we also factor in for a base kind of baseline growth for our ex-China sales, which, of course, is run by our partner. So conservatively speaking, we are very conservative to give this low-end guidance, but you can expect the midrange of that is almost like a 36% growth. between $330 million to $450 million is about [indiscernible] that is more like 36% growth versus this year's 2025 performance. So I think this is a guidance that basically can reflect the business growth as well as the potential if we have licensing, of course, we won't take all the upfront income. We will potentially apportion part of the upfront income and factoring into the upside.

Next question coming from Goldman Sachs, Paul Choi.

My question is on savolitinib and assuming clinical success coming up here with SAFFRON, can you maybe comment on how you think Tagrisso, savolitinib combination would be sequenced in the treatment paradigm given the recent launch of J&J's RYBREVANT bispecific? And just how you think about guidelines evolving directing oral options versus bispecific options?

Yes. Thank you. So George, do you have any color to share on this?

Yes. This is -- I think this first thing is this provides an oral -- 2 oral products for those EGFR-resistant MET amplification patients. So this is -- we provide very efficacy and as well as convenience. But we do know the J&J bispecific antibody do provide another option, but all depends on doctors' perception regarding how the treatment paradigm shift is still precision medicine win the game or not. The testing, the secondary testing win the game or not. So it depends on how AstraZeneca is shaping the [indiscernible].

Thank you, Paul. I see a couple of questions in the chat box. Some of that actually has been kind of answered already. There's a question -- Johnny, the question is what is the thought about the need to decide appointment of a permanent CEO? Or are we happy with the current situation?

Okay. I think we have -- the company has made an announcement in August. I think no status change as yet regarding the announcement. So Dr. SU is focusing on his health right now. And yes, so we have this interim arrangement. And as you can see, we have a lot of talents within our management team. Today, we have Dr. Dai and also we have Lorenso Chiu joining this webcast. So the company has been running for 20-odd years, and we have a very loyal and also capable talents within our talent pool. So -- and everything has been running very, very smoothly and also progressing in terms of our pipeline as well as our commercial strategy, everything it is now working as per plan.

Thank you, Johnny. I don't see any outstanding questions right now [Operator Instructions] There's another question talking about SAFFRON readout delay from first half to second half. But as Dr. Dai has mentioned, the most likely scenario will be around mid-'26. If no further questions, Johnny, would you like to do a concluding remark?

Thank you again, everyone, for spending the time to attend this webcast. And if you have further questions, please by all means to feed through our IR colleagues. Thank you.

Thank you, everyone. And this concludes our results presentation. Thank you very much. Thank you very much.

Hello, and Welcome to Deutsche Bank's Virtual Investor Conference, dbVIC. This is Zafar Aziz from the Deutsche Bank team. I'm pleased to welcome our next presentation by HUTCHMED from Hong Kong. Before I introduce our speaker, a few points to note. [Operator Instructions] All of the presentations were recorded and can be accessed by the Deutsche Bank website, adr.db.com. I'm very pleased to welcome HUTCHMED, over to you.

Thank you very much, Zaf. Thank you, everyone, for joining the presentation of HUTCHMED. My name is David Ng. I'm the Head of IR and Capital Strategy for HUTCHMED. Together with me, we also have Matthew Kwong, VP of Finance, joining us today. So for those who are already familiar with HUTCHMED, welcome back again to listen to our latest update. For those who are new to our story, we definitely have a lot of exciting things to share with you about.

And before we formally start the usual safe harbor statement and disclaimer. Basically, the performance and results of operations contained in this presentation are historical in nature, and past performance is no guarantee of future results. So let's start.

We have this summary slide that I think quite succinctly cover our past, our current and most importantly, our future direction. On the left-hand side of this slide, you have the circlesing global commercial success, and we are very happy to have our innovative drug FRUZAQLA doing very well during first half this year with sales up 25%. Again, for those who know this, we have been selling in China for a couple of years, but we got FDA approval in 2023. Our marketing partner, Takeda, has been doing a fantastic job ramping it up in the U.S., in Europe and Japan over the last a little bit more than a year, and it has been doing great.

So of course, this not just validate our science, but it also provides us with a very strong financial foundation, helping us to be profitable since 2023, '24, and we expect to remain self-sufficient in our capital funding in the upcoming years, thanks to this innovative drug finally materializing in global sales.

And we are expecting the second one. This is a drug called ORPATHYS for lung cancer. It has been going through both trials in China, global trials. The trial name is called SAFFRON. We anticipate completion very soon, and then the readout of the data will be first half next year. Our marketing partner, AstraZeneca, when this product potentially get approved in the U.S., we will be commercializing this one. We hope that will be sometime around 2027.

So I think with these 2 products, we hopefully will have 2 commercial global products supporting both our financial as well as validating our science. I probably won't go over into too much details of the near-term catalysts. By the way, this presentation is also on our homepage. So if you miss anything, you can definitely go back to download this presentation on the HUTCHMED homepage. We do have a couple of upcoming catalysts in the next 12 months, definitely very relevant for our stock price performance.

But I definitely want to spend more time today to talk about our future, which we have a new generation technology platform called ATTC, antibody-targeted therapy conjugate. I think many of you have already heard of the term called ADC, ADC, right? I think you can look at our ATTC to be the next generation of ADC and even more improved version of ADC, focusing specifically on improving the safety and the toxicity of this kind of molecules initially target oncology, but maybe down the road, it may also have potential autoimmune application.

The very first drug candidate coming out from our ATTC platform, that one is called A251. We have just presented the preclinical data in the EORTC conference just a little bit 2 weeks ago in Boston. And right last Friday, we also host an R&D Day, both online and offline, explaining even in more details by our Chief Medical Officer on our first molecule. And for those who may have missed that, again, the webcast replay is also on our homepage for our ATTC platform.

The reason why I say this is very important is not -- is that because this is not just one molecule. If this ATTC platform works, it will generate many, many more drug molecules. Of course, it's still at an early stage. We have got some very good preclinical evidence. And then our plan is to get it into patient Phase I trial in December this year. We had already got the IND approval in the U.S., and we are pending to receive the IND approval in China. So expect 2026 next year to be a year full of news and events coming out from this platform.

Apart from the science, which we think we are global first in this so-called ATTC category, the other thing that we bring a lot of attention to this is the potential out-licensing opportunities. We have been attracting a lot of interest from global pharma into this platform, and there are possibility of BD opportunities in the -- when we disclose more clinical data down the road.

So I think on this slide, we do have very solid financial foundation that make us very self-sufficient, not relying on the capital market for further funding. But at the same time, the most -- more important thing is our ATTC platform, which if start to generate good results. It will provide us with an even bigger pipeline of products that we will -- can bring to patients in needs down the road.

Now we do have a very big slide deck here. So apologies for not going through every single slide. But I will just jump to this one right here, which is our first half sales of some of our key products. Again, like FRUZAQLA has been doing quite well, up 25% first half this year. For those who have been following us even more closely, you may have looked at some of our marketing partner third quarter sales. And then we roughly have about quarter-over-quarter growth of around 10% for both the FRUZAQLA, which is overseas fruquintinib. And then also for domestic fruquintinib, we also start to see some quarterly improvement.

Now -- but again, like this is the present. Let me jump a little bit to the slide where we talk about our upcoming future potential. So first of all, our late-stage pipeline is very solid. For our fruquintinib, we had already been selling it for colorectal cancer. But since early this year in China, we also got approval for a second indication called EMC, endometrial cancer. This is a combination therapy with another PD-1 drug that we can address the market.

And I think we also have the third indication called renal cell carcinoma, RCC, which we have already presented very impressive data in ESMO, the ESMO conference just last month or early this month. And we have also submitted or filed the -- to the China NDA, which if everything goes smoothly, the approval probably would land around middle next year potentially. So with that, we will actually have 2 more indications for fruquintinib to support its further sales growth in China.

For the other product, savolitinib, we had got a second indication approved on June 30 this year. This is the second-line lung cancer focusing on the MET amplifier. MET, of course, is a biomarker, roughly in 1/3 of the patient population in the second-line EGFR setting. So it's definitely a very sizable patient population. And we are the only one around the world with such late-stage data focusing on the MET-specific patients.

For the overseas trial, similar to this SACHI trial that you saw there, the overseas counterpart is called SAFFRON. I mentioned briefly just a moment ago that our marketing partner, AstraZeneca is close to completing the recruitment and the data readout will be first half next year according to AstraZeneca guidance. And if, again, everything goes smoothly, potential U.S. approval in 2027, which may bring our second innovative drug to be globally commercialized.

Back in China, we are also working on another even more impressive trial in the first-line setting. This is a trial called SANOVO, fully recruited. Again, this is also a very highly contested market in the first-line lung cancer space for the MET overexpression, it's a very decent market size as well, ranging from 30% to 50% of the first-line lung cancer patients have overexpressed MET proteins. So if the results are satisfactory, this will also address a very sizable market.

The third drug called surufatinib, the thing to look out for is December, we will present the pancreatic Phase II data at a conference. So watch out for that one, and we are planning to -- if the data is satisfactory to roll into Phase III trial. Again, pancreatic cancer is what a lot of people call cold tumors, very tough-to-treat cancers. And we are using our surufatinib in combination with another PD-1 and chemotherapy to target this tough-to-treat cancer.

I'll skip the next one and go straight to the blue one called sovleplenib. This one, if you remember, we presented very impressive data, durable response rate of around 51% and this is compared to most of the new modality just hovering around the 20% to 30% durable response rate. Unfortunately, we had some CMC issues earlier this year, and we have to change to a new formulation. We don't have to redo the Phase III trial, but we do have to resubmit the data. The time line we now anticipate to resubmit the data for the China authorities will be first half next year.

This is for the indication of ITP, which is basically blood platelets being too low in the body and you kind of bleed very easily. It's a chronic disease. It's an autoimmune disease. It's definitely a new area that we are very excited about, and we plan to commercialize it in China when it potentially get approved hopefully in 2027. It is also working on another indication, a little bit rare disease called warm AIHA, second-line setting. The data will be probably around early next year to present the data. So if that is also successful, sovleplenib will have 2 potential indications addressing a very sizable market population.

Now so this is -- this slide and many of the slides that I just went through for those who are familiar with HUTCHMED, you probably have seen it a couple of times before. What I'm going to show you next, I think, is pretty new. So the next slide, we're going to talk about the early-stage pipeline. Focus on the bottom 3 coming out from our ATTC platform. The first one is called A251. And we disclosed just 2 weeks ago basically the composition of this.

Now let me also jump to the next slide here, where we talk about the structure of this ATTC. It's made up of a large molecule and antibodies, right? And we disclosed that this antibody is a trastuzumab biosimilar, a HER2 targeting antibody. And it's going to have a linker, a cleavable linker. So far, it is still quite similar to the ADC that you've seen out there. But what differentiates us from all our peers is for the payload, instead of using a nonspecific chemotoxin, we are using a specific small molecule drug, right? So instead of like a payload, we use a small molecule drug. As the payload, which means that it will be even more selectively targeting certain mutation or certain mutated pathway, which is manifested more strongly in certain oncology indication.

And this concept, I think, is quite easy to understand, but we actually don't have anyone trying this so far as far as we know in the clinical space. So we probably is still the first company pushing this ATTC composition into clinical trial globally first in the upcoming months.

The other thing that is also quite new is this particular small molecule drug, we call PI3K/PIKK. It's basically focused on a pathway called PAM, PAM pathway. there are no commercial drug on the PAM pathway yet. And the reason is that it's a very toxic molecule. So I think the scientific community is already quite well aware and has a good consensus that this particular molecule targeting this pathway is very effective in eliminating tumors. Unfortunately, it's just too toxic. So I think this is a very important point, right? For our ATTC, we are not just limiting to this HER2 with PI3K combination. We're going to have different combination, and a lot of investors ask us what other are we thinking about?

Think along the line of small molecule drug, which may be known to the scientific community, but was just too toxic. So it was not able to be easily commercialized as a drug or approved as a drug. But when this small molecule is loaded onto this ATTC platform, it becomes very selective. It becomes very destined for the tumor tissues. And then this toxic small molecule or this very potent small molecule will be deliberately delivered just to the tumor tissues and take its effect on eliminating the tumor tissues. So this is basically the concept, right?

And as I said, we do have a couple of other combinations that we're working for. We have not disclosed that yet. We kind of disclosed the code name -- the second molecule is called A580. We anticipate entering clinical trial around middle part of next year. And then the third one is A830. We targeted towards the end of next year to end the clinical trial. And as we disclose more data coming out from this #2 and #3, we will also disclose the actual composition, right?

But again, think along the line, small molecule drugs that are very effective, but were just too toxic in the past to be turned into a drug for cancer patients. Now with this platform, we can load it on our ATTC, and it become like really targeted to the tumor tissue.

Now of course, just a caveat here, we have done a lot of very good work in the preclinical stage, in animal stage. We haven't tried on human yet, right? So -- and then that's why as the human trial kicks off in December and when the data start to roll in 2026, it will be very exciting for us as well as our potential licensing partners down the road to look at really how safe this ATTC platform can be, right?

Now just to dig a little bit deeper into this market that we are looking at. In fact, this particular slide that we created just last week even surprised me. I think many of you are much more familiar with some target like EGFR, like HER2, right, or maybe even RAS. Very few people talk about this PAM pathway. And it turns out that it is present in 50% of the solid tumors globally, right? So this is not a small number. And why do we know about this or why we're not more familiar with this is because this pathway or molecules targeting this pathway is just too toxic. It works very well, but it's just too toxic, right?

So -- and then for some of the major cancers, which have this PAM pathway alter, we kind of outlined it here. And again, because we use HER2 as our large molecule, we also present some of the prevalence of different HER2 expression in the breast cancer space. And the clinical trials that we plan to kick off at this stage, this is our plan. And you may notice this is also slightly different from our tradition -- the tradition of HUTCHMED by doing things one at a time, right? We want to go a little bit more aggressive this time. We are working on different tumor in different cohorts at the same time.

And you may notice that we are also working on the later line, like the second line, third line indication as well as the first-line indication at the same time. Why? As you may know, the competitive landscape has dramatically changed in China last 2, 3 years with a lot of these licensing deals providing a lot of funding and a lot of bullet for our competitors to work faster and go into innovative modality earlier and sooner.

So we need to also pick up our speed. We now have a much stronger balance sheet of about $1.4 billion cash, and we want to put this cash into the right use by working on multiple trials. And we also -- actually, if you look at this, we also have a cohort looking at HER2 low, which is also a very sizable market out there. We haven't disclosed the tumor. I'm pretty sure we will disclose it in the near future. But these are all very large addressable market that we are working on. So that's kind of our current plan for ATTC. And then this is another slide just to give you an idea of the precedence of this PAM alter pathway in different type of cancers. And then, of course, we have the HER2 antibody or target preference in different type of tumors.

But definitely watch out for one thing that we are trying to see whether it works for HER2 low. So not just HER2 positive, but also HER2 low, which again is another big market out there.

Now again, like we haven't disclosed what other antibody that we are working on. Someone may say like why HER2, why not something more -- even more crazy or even more innovative than that. I think at this stage, this PAM or this PI3K small molecule is new. It's not new to us, but it's new to the clinical space. We haven't put it into clinical trial yet. So we want to kind of conserve the riskiness to that part, whereas for the large molecule part, the antibody part, we are picking HER2 deliberately, which is a very good, well established, very well-known profile antibody.

And also for the linker, we kind of have not elaborated too much on, but this is also a very well-established linker that we are using. And the most innovative part or the part that the clinical space haven't seen too much data is actually the small molecule part, the small molecule payload.

So the upcoming few months, we are going to see 2 things. Number one, whether this small molecule drug does work well for cancer. Number two, whether putting this large molecule linker and a small molecule together, whether this construct conceptually is stable enough when injected into human body and whether this will have good efficacy and more importantly, safety.

One last point I want to emphasize about ATTC is that we call it a chemo-free conjugate. Again, like this is in contrast to the ADC out in the market or under development, which still rely on the chemotoxin, which is kind of like a nonspecific toxin attacking all the tissues.

With our chemo-free ATTC molecule, many people are asking us, are we going to replace chemotherapy or are we going to replace ADC. I think the path -- at least at this juncture, the path that we want to take is not necessary to replace, but to be potentially used in combination, in combination with chemotherapy, of course, preferably in the earlier line setting and also in combination with ADC out there. We've got very good animal data showing that it does work very well, now is to put the test into human trial.

I noticed that I have roughly 5 minutes left. So I'll just pick one slide, and I will just go into some of the questions that is already on the line. So this is kind of our road map, still mostly focusing on our existing pipeline, not too many ATTC molecules out there, right? But it's still a very busy, very eventful next 2 years even from our own pipeline. But I would have to say that if this ATTC platform starts to deliver, the value or the impact from this ATTC platform may be even bigger than what you see on this particular slide coming out from our established late-stage pipeline. So I will wrap up here, and I will go into a couple of questions here.

So first question, let's see, can you elaborate on China growth driver versus U.S., EU market?

I think China continued to present one of the largest patient population, but then the pricing is a little bit compress, right, whereas the U.S. and EU market definitely have a better pricing for our drug. So we will continue to do both, right? China is our home base. We developed many innovative drugs from our excellent scientists from China, but we will definitely try to bring this drug to all around the world, definitely include U.S. and EU market.

The next question is, can you discuss the clinical time line and upcoming milestone for ATTC program?

Yes. So the 3 that we have disclosed, we expect to kick start the first one December into human trial and then the second one around middle part of next year and then the third one towards the end of next year. So hopefully, by the end of next year, we will have 3 ATTC molecules in clinical trial.

And next question is, how is HUTCHMED leveraging strategic partnership to accelerate?

Very good question. I think we do have a very strong balance sheet, right? But we think that with our many molecules coming out from the ATTC platform, we are definitely very open to out-license some of that even in the early-stage development, right? Because it not just validate -- and we're definitely looking for multinational pharma to be a potential partner, right, because it's not just going to help validate the science, but it's also going to bring in potential upfront payment, which will again help us to be very self-sufficient to support even a bigger pipeline coming out from the ATTC program down the road.

And the next and last question, a little bit similar, how do -- how will we allocate the capital and commercialization of our oncology drugs?

For overseas market, we will look for multinational partners. We've enjoyed a very good partnership with AstraZeneca with Takeda. For China, we plan to use our own sales team to do the commercialization. We have about 700 people. They are very well trained. They are definitely ready for more products to commercialize in China and to support our home base.

With that, I think I have about 30 seconds left, and I want to thank everyone who has been listening to our presentation and everyone who has been supportive on HUTCHMED and definitely looking forward to an even more exciting 2026. So thank you, everyone.

Hello, everyone. Good evening and good morning. Thank you for joining HUTCHMED 2025 R&D Day event. For your reference, you can go to our website to download today's presentation slides.

The performance and results of operations of the HUTCHMED Group contained within this presentation are historical in nature, and the past performance is no guarantee of future results. [Operator Instructions]

So now let me welcome our CMO and Head of R&D, Dr. Michael Shi, to start the today's presentation. Michael?

Thank you, Ng. Good morning, good evening, everyone. Happy Halloween. And so today, I'm going to give you a research update for HUTCHMED pipeline. So today, we're going to talk about the -- our main antibody target therapy conjugate platform and really showcase some of the new next-generation platform. And also recently, last week, we actually presented our first candidate, HMPL-A251 at the EORTC meeting in Boston. So I'm going to highlight some of the progress and show you the results and our overall preliminary development plan strategy. And then I'm going to show the late-stage pipeline progress and with a closing remark and then we're going to start a Q&A session.

Okay. So for the ATTC platform we introduced to the investor early this year is really the new development for the past 3 years at HUTCHMED. We're really looking at some of these progress and the platform. So before we go that and we really talk about the current development in the toxin-based antibody drug conjugate, ADCs. As we know, there are 19 ADC has been approved worldwide. And despite the design and the rationale expanding the therapeutic index, the traditional toxin-based ADC also have a very similar toxin profile. And microtubule and the tubulin isomerase inhibitor and both have some common feature for toxin-based toxicities such as myelosuppression, thrombocytopenia and hepatotoxicity and some of the ocular toxicity or neurotoxicity. So far there's really the limitation. There's certainly room to improve to overcome these challenges. And the HUTCHMED antibody target therapy conjugate really designed to target a protein required to [indiscernible] cancer growth.

And one of the important feature of what we believe it has the synergistic combination activity with antibody because the antibody we chose really have the antibody and the function to really have a potential synergistic effect. And more importantly, we know the ADCs has very difficult profile to combine with the traditional chemotherapy, which is often required for frontline chemotherapy. So we think the ATTC will overcome this chemo-resistant and also have the potential to be dosed long term. And from toxicity perspective, although the -- it have the antibody-based toxicity but we believe the antibody target therapy payload have the low on-target and off-target tumor toxicity. And also, they bypass some of these traditional small molecule systemic toxicity, for example, liver toxicity and QT prolongation, et cetera and low myelosuppression and also support a long-term use. So we think this just will be a unique platform to really enhance some of these and overcome some of the resistance and difficulty for the toxin-based ADCs.

So when we select these development for ATTC, really selecting some of the functional antibody and conjugated with the target therapy, which traditionally a small molecule have poor solubility and very hard to link the antibody. So we're really working on the linker and the payload to have this ATTC platform develop. And with the lower free target therapy in the circulation and also have a wider therapeutic window compared with the oral systemic exposure. And also, it has a great opportunity because they can combine with the other therapies, for example, target therapy, immunotherapy and more importantly, the chemotherapy. So this will potentially have a opportunity to be used in the frontline. So to show some of the -- highlight some of the first target therapy, the -- really the unique invention here is the target therapy payload targeting the PAM, PI3K/mTOR pathway. So the PAM pathway, PI3K/AKT/mTOR pathway is very attractive therapeutic target because it has a very -- cover a very broad range of the tumor type, have a high frequency mutation in some of the most common tumor type.

For example, in breast cancer, the PI3K PAM pathway mutation representing about 70% of the patient -- breast cancer patient. Also in endometrial cancer, for example, has very high mutation rate. Also in the other common tumor type, it also have a very high frequency. So -- and also, this is in the development stage, there are quite some small molecule, pretty much the previous effort focused on the small molecule development but have a very few success. And also talking about the mutation is really play a role in the toxin-based ADC resistance. So this is one of the report last year from ESMO showing that HER2 ADC disitamab vedotin RC48 in breast cancer patient type. And in the clinical study in the overall patient population, the PFS and ORR is better but with patient with PAM-altered pathway really show for poor prognosis activity. For example, the PFS, that's actually lower, response is lower because this driver mutation really leading to the drug resistance for ADC product.

And also in the DESTINY-CRC01, also showing the driver mutation for PIK3CA and also RAS mutation, patients with these mutations also have a lower response rate and shorter PFS compared with the wild-type patients. So really leading to -- there's opportunity to really improve to develop a target therapy as a payload to overcome this resistance. I also mentioned about the traditional development for PI3K/mTOR pathway, really focused on small molecule. There are quite a pipeline of development, including multiple companies invested in this PI3K inhibitor development and -- but with very few success. And the first generation and second generation pretty much halted due to the systemic toxicity. And later on, there are mTOR inhibitor, for example, everolimus, PIK3CA alpha, alpelisib and capivasertib is AKT inhibitor, leading to the approval but they also have a pretty hard to handle tolerability profile and also the overall survival has been hampered.

And there are -- 2 weeks ago, we see the new PI3K inhibitor gedatolisib really showcase some of the activity in the breast cancer but it still has a very high difficulty in toxicity, for example, mucositis and some myelosuppression as a side effect. So targeting PAM pathway alteration really showing as a promising approach for breast cancer. For example, in the slide here, we show in the overall breast cancer patient population, you can see the PAM pathway mutation, including PI3K mutation, AKT mutation and PTEN loss, representing about 70% of the patient with this mutation. In HER2+ patient population, including hormone positive or negative patient population, the PI3K PAM pathway mutation is representing close to 40%. And in the HER2- patient population, triple-negative patient population, these mutation even have a higher presence.

So really presenting a big opportunity for developing PI3K inhibitor targeting breast cancer patient population. In the gedatolisib study, we do see there is a improved PFS and activity in not only in overall patient population, representing inhibiting target in HER2+ patient population also show good activity and -- but adverse events such as stomatitis also pretty high. Okay. So here's the profile for our pan-PI3K pathway inhibitor, PI3K/PIKK inhibitor. And this is HM606 (sic) [ HM609 ], in short, we represent 606 (sic) [ 609 ]. This is our first targeted PI3K inhibitor using as a payload. So the profile for this molecule and showing in the kinome, you can see the major inhibition really showing focus on the PI3K and PIKK activity is very high selectivity and very few -- small off-target activity. And this is the profile compared with the other kind of PI3K or PIKK inhibitor. Gedatolisib and dactolisib and buparlisib, you can really see 609 has a very robust and potent inhibition against all these PI3K and PIKK pathway.

Here's the biochemical characterization of this -- our first ATTC is the A251. And as we can see, using this we look at the payload, you can see this has a pretty potent inhibition of the PAM pathway. When this pathway is activated, it's commonly in the breast cancer cell lines, you can see very robust dose-dependent inhibition of the PAM pathway, including AKT S6 or so. And also in the PIKK pathway, when you enhance the PIKK pathway by treating with bleomycin, you can really activate all this DNA repair process and using the payload 609, you can see also a dose-dependent inhibition of this pathway. And also in the panel of 130 cell lines, we can see in many cell lines with mutation of a PAM pathway, HER2 pathway alteration, RAS/RAF pathway mutation and other cell lines. 606 (sic) [ 609 ] has a very potent activity with IC50 about 1 nanomolar. And also on the right-hand side is the cell growth inhibition of 609 by tumor type. And also show -- demonstrate a nanomolar range and also high potent activity across many different tumor cell lines.

So now let me talk about the antibody part. The first proof-of-concept molecule where we develop is using HER2 as a antibody. We all know HER2 alteration really leading to a poor prognosis in cancer, in many tumor type. For example, HER2 amplification and overexpression has been shown is as a poor prognosis factor and HER2 amplification or overexpression lead to the patient with a shorter half-life -- shorter lifespan. And also HER2 overexpression and amplification really cover many tumor type. So what we also looking at the anti-HER2 therapy is really, for example, developed by trastuzumab is a functional antibody with intact Fc and leading to ADCC activity. So it works by blocking extracellular domain cleavage to prevent the formation of its active form of HER2 and also block the dimerization of the molecule and reduce the signal transduction pathway and also mention the antibody leading to the antibody-dependent cell-mediated cytotoxicity and also the HER2 antibody downregulation through the endocytosis through the lysosome.

So to sum up for our concept and for the development of ATTC, we use HER2 as a therapeutic antibody and PI3K/PIKK pathway inhibitor as the payload. This provide opportunity to really inhibit the most major oncogenic driver and the downstream signaling pathway of HER2. And it has the potential to overcome the resistance for trastuzumab-based therapy and also the antibody and the payload will have a synergistic activity to -- with the enhanced antitumor activity. So this pan-PI3K-based HER2 ATTC is really expected to increase the efficacy and synergism and also improve the safety profile to overcome some of the narrow therapeutic window for the traditional PI3K inhibitor.

So now let me move to the first candidate, A251. We showcased this molecule at the EORTC meeting last week in Boston. So here's the structure for PI3K -- the A251. It has the payload 609 and is a highly potent PI3K/PIKK kinase inhibitor and has the potential synergy with the HER2 antibody. And we also show you some of the data we have the potential for combination with chemotherapy as ATTC and also show the bystander effect. The [indiscernible] portion is the HER trastuzumab biosimilar and with a credible linker and with the antibody -- drug to antibody ratio of 4. Here's the in vitro binding activity. It does show A251 and the HER2 antibody has a very similar binding activity. And also this figure show the internalization of the antibody A251 ATTC and also the naked antibody.

So at 37 degrees, we can see the internalization. On the right-hand side, you can see the intracellular trafficking of the antibody drug conjugate. So here is the blue color is showing the nuclear staining and the red color is really with the HER2 antibody. Green color is showing the lysosome. And when you incubate cells, you can see it has a time-dependent internalization of the antibody, both the naked antibody and also the A251. As you can see, with the time when you merge the signal, the red color and the green color will overlap with the times of incubation, really showing the antibody has been internalized into the lysosome. And also, we show you the activity for payload 609, now for the whole antibody target therapy conjugate has a similar feature as the payload alone when you do the in vitro cell inhibition assay in HER2+ PI3K mutant cell lines. We can see a potent inhibition, dose-dependent inhibition of the, first of all, AKT S6, for example, really showing the target pathway inhibition and leading to clear the pathway PARP inhibition and leading to apoptosis.

And also on the right-hand side is the PI3K -- PIKK pathway inhibition showing this molecule also have a in vitro inhibition of the PIKK pathway and also leading to the DNA damage when you use the A251 has increased the DNA damage. And also next, we show the activity in the panel of cell lines for A251, showing the growth inhibition on the left-hand side. You can see in the 26 cell lines we have tested, HER2+ cell line with PI -- PAM pathway alteration or without alteration, it has very robust potent activity, actually 0.2 nanomolar range to have a very good tumor growth inhibition effect. And in HER2 low PAM-altered pathway, it still demonstrated potent activity, although the potency compared with the HER2 overexpressed positive patient population, it has less potency and also has some less magnitude [indiscernible] in HER2 low, the cell lines.

And here down the right-hand side, we show the bystander effect. In the HER2+ cells, we can see the A251 showing very potent bystander tumor killing effect. And it doesn't work on the HER2 low cell lines but you co-culture the HER2-positive and HER2 low cell lines, you can clearly see the robust tumor killing with the bystander effect. And also, we test this molecule in the -- in HER2 resistant cell lines. So one, on the left-hand side, we can see the comparison of the A251 with the HER2 in cells, in breast cancer cells with using the siRNA silencing of the SLX4, which is one of the key gene to turn on the resistance because it's one of the DNA repair enzyme. And when you're really silencing the SLX4, you can see a right shift of the potency of the payload DXd or DS-8201 in HER2. It has less -- need a higher concentration and also the less -- the inhibitory effect, compared with the A251, the -- compared with the payload itself and A251, you can see there is no right shift and the payload and ATTC maintain the same potency to inhibit this resistant cell line.

And on the right-hand side is the developed cell line resistant to -- in HER2 or the payload. And you can see, again, right, the DXd treated cells and in HER2 treated cell have a right shift and less potent killing effect compared with the parent cell. But in the payload 609 and ATTC A251, you don't see -- you don't observe this right shift and maintain the same tumor killing effect, cell tumor killing effect. And here is the, one of the proof-of-concept study we have done for A251. And here, you can see the black label is the vehicle treatment and the red color is the payload 609 itself at 0.5 milligram per kg IV injection biweekly. And the pink color is the trastuzumab plus 609. You have also increased cell growth inhibition. And A251 at 10 and 30 milligram per kg, really showing robust tumor inhibition activity and causing tumor regression.

So this is very important because this is HER2+ and PTEN loss xenograft model. We can see a single dose injection of A251 can have 2 weeks sustained tumor suppression, unlike the small molecule. So you need multiple dosing to have a modest antitumor effect because this is actually the MTD level of the payload for 609. And also on the safety side, you can see this -- on the left-hand side is the same model. You can see the ATTC A251 and then that does not lead to the body weight change. But the small molecule, 609, the payload and the 609 plus trastuzumab, you actually see when you dose the small molecule, you can see actually a quite significant body weight loss and they recover, when you dose again, it will lead to additional body weight loss. So this is pretty much the -- this is really the maximum tolerated dose for this small molecule payload. And so as you can see, really in the preclinical model, you can see this activity of the A251 has a more safety profile compared with small molecule or small molecule combined with the company -- with the antibody.

Also on the right-hand side is a very classic example because the small molecule 609, when you see the dosing, the [indiscernible], it has a very transient and high glucose increase, same with the 609 plus antibody. On the other hand, A251, the glucose level remain unchanged because the PI3K inhibition leading to hyperglycemia is really a classic hallmark for this class of PI3K inhibitor. So in this preclinical setting -- model, we really demonstrate using the ATTC concept, you can really increase the safety profile for this PI3K inhibitor because it's a targeted delivery of this conjugate into the tumor cells, leading to the release and inhibited the tumor unlike the small molecule, really have a higher systemic exposure and lead to HER2 PI3K pathway inhibition leading to the toxicity. We also test the A251 in multiple xenograft model. And here is the 2 model we have shown is the breast cancer cell line with HER2 overexpression and the PI3K mutation. And also the lower one is the ovarian cancer model with HER2 expression and HER2+ PI3K-mutated model.

On the red line is the 10 milligram per kg in HER2 as a control. I can see in these 2 models, we can see a faster and deeper response for A251 leading to the tumor growth inhibition compared with the DS -- compared with the HER2 itself. Here, we also test the panel of HER2 low PAM-altered cell line, endometrial cancer cell line. And in the -- with the tumor xenograft model. Again, we can see in HER2 low model, we can see a more rapid tumor growth inhibition of A251 compared with -- in HER2 in the [ upper ] model. And in the cervical cancer model, we can see the activity of A251 is similar to -- in HER2. We further test some of the model without PAM pathway alteration. In HER2+ PAM nonaltered xenograft model, we can see in HER2 and A251 has about similar antitumor activity. So in all of the model we have test, we can see the A251 pretty much have a stronger activity or at least comparable to DS-8201 in HER2 at the equivalent dose level.

Here's the pharmacokinetic profile for A251. We can see on the right-hand side, you can see a single dose injection of the A251. We can see the total antibody and the antibody and A251 have the high sustained exposure. And 609, the free payload, which has remained very low concentration compared with the conjugated ATTC. And the right-hand side, we also conduct a stability -- plasma stability study compared with -- in HER2 A251 have a more stable half-life compared with the -- in HER2 in the monkey and the human plasma. Here's the in vivo pharmacodynamic activity for A251. We have the vehicle control and also A251 10 milligram per kilogram IV injection and monitor the time course for the phospho-AKT, phospho-S6. You can see there's a time-dependent inhibition of this PAM pathway. And H2AX [indiscernible] H2AX is a marker for DNA breakage. You can see the increased DNA damage and also leading to increased cleaved caspase which is [indiscernible] representing the apoptosis.

And the CD68 is a marker for macrophage inhibition. You can see the macrophage infiltration into the tumor cell. You can see really leading to the ADCP, antibody-dependent cytotoxicity. And also, we look at the distribution of the payload in the tumor cell. In the tumor cell, we can see a sustained and high exposure of the payload into the tumor cells and the [indiscernible] in the plasma level is actually remained low. And again, they just representation of the inhibition of the pathway leading to the PAM pathway and -- with inhibition leading to apoptosis and DNA damage and ADCP activity. So in summary, A251 is the first-in-class PI3K/PIKK inhibitor conjugated with HER2 antibody, has robust and potent antitumor activity in HER2+ model without or without PAM moderation, also showing quite good activity in HER2 low tumor model with the PAM mutation. And also it has a favorable PK profile and have a much improved safety profile compared with small molecule payload itself.

And so we have completed the GLP tox study and filed a China and U.S. IND. And we already received FDA clearance for this U.S. IND and our Phase I clinical study is starting to enroll patients later this year. Here, I'm going to show you some of the high-level clinical development plan. Of course, the Phase I, we're going to start with the single dose escalation. We are now -- we are enrolling HER2+ or low patient population. And PAM pathway alteration will be tested retrospectively. It's not the requirement for enrolling patients. And further dose expansion will be tested in HER2+, PAM+, HER2+ and PAM nonaltered pathway patients. And also we'll test the HER2 low and PAM mutated patient population. And we will further expand in multiple tumor type with or without the PAM alteration. And also, we will test when we define the dose for a single agent, we also will start the A251 in combination with standard chemotherapy in the earlier line, in the frontline setting.

And also, we're going to test the solid tumor in the HER2 low patient population with the PAM alteration. So here is, as you can see from this molecule with -- we have pretty mature HER2 pathway functional antibody and also the very broad PI3K inhibition. So the PAM pathway is quite common compared with other driver mutation, ALK alteration, EGFR in Western patients and HER2 amplified mutated patients. So PAM pathway alteration really representing a very broad range of tumor type. The new incidence for all these cancer type is very high. And also in the breast cancer, we can see HER2+ patient population represent a 15% to 20% patient by the standard testing. And as we know, HER2 low patient population also have a very robust percentage, representing 40%, 50%. And the HER2- patient population is a smaller percentage. So this will really provide a good opportunity and targeting a larger HER2 expressed patient and also with the PI3K mutation because HER2 is also a one of the downstream -- because PI3K is also downstream of the HER2 activation pathway.

So we think this molecule really can cover very broad range tumor inhibition in the breast cancer area. And so just thinking about the HER2- second-line breast cancer with the gedatolisib, for example, recently demonstrated activity, the market size representing about $5 billion. So we believe even HER2-, part of the significant portion of the patient will have HER2 expression. And these will -- can still potentially be patients benefit from the A251 in addition to HER2+ patient population. So this molecule really representing a good opportunity for the broader tumor type development in the future. So I show you the first molecule, A251, as the -- our leading molecule, which is -- will enter clinic later this year. And also here, you can see the PAM pathway alteration really cover very broad range of tumor type, lung cancer, breast cancer, colorectal cancer, breast cancer, for example.

And the HER2 pathway expression also show pretty -- cover broader range of the tumor type. And here represent our opportunity for our first molecule. And by the same concept, we think other important antigen, right, TROP2, EGFR, for B7-H3, for example, all these have a very broad coverage for different tumor type. By leveraging the payload, not only the PI3K/PIKK inhibitors 609 but also other target therapy, which have -- inhibiting major pathway driver mutation cell lines. We think this ATTC platform can really cover very broad range of tumor type, representing a huge opportunity for the development. So our first molecule has already get a U.S. IND clearance and starting enroll -- will start to enroll patients soon. And the second molecule, A580, which is with a different antibody and will -- we have not yet disclosed but we are targeting to have the Phase I initiation early next year in the China and the U.S. Third molecule, A530 (sic) [ A830 ] and will also enter the clinic in the second half of 2026. So we kind of update you about the ATTC platform and the lead molecule enter the clinical development.

We'll -- I'm going to cover some of the new development in the late-stage pipeline. So HUTCHMED has really developed a deep pipeline covering multiple tumor types. Our first approved product, fruquintinib, we already approved in the colorectal cancer and worldwide ex China has been covered by Takeda. And in China, we also continue to develop additional indication. FRUSICA-1 was reported already in endometrial cancer. So we get NMPA approval for pMMR endometrial cancer December 2024. And also second-line RCC, we have showcased this FRUSICA-2 trial data at ESMO 2 weeks ago in Berlin. I'm going to show you some of the highlight of the data. And the NDA has been submitted and under review in NMPA. Our expectation is that we're getting approval late next year. Also MET inhibitor savolitinib also making tremendous progress. And we show the clinical data of SACHI in second-line EGFR mutated MET amplified patient population in combination with osimertinib, demonstrate the robust clinical improvement and it was approved by NMPA under fast track review in June '25.

And also our partner -- global partner, AstraZeneca has also presented data in SAVANNAH, really demonstrate the high and clinically meaningful in durable response. Also, we are all very much looking forward to SAFFRON, which is the global AZ lead study in second, third-line EGFR mutant -- EGFR mutant MET amplified or overexpression lung cancer has a data readout next year. And SANOVO is the first-line MET overexpression patient population in combination with osimertinib. We have fully enrolled the patients in August. And also, we are anticipating the GC, gastric cancer in MET-amplified patient. We are conducting single-arm registration trial with the patient enrolled in April and the readout with the potential NDA in this year. And SAMETA is in the papillary renal cell carcinoma, is also lead by our global partner, AstraZeneca.

And also the other approved products, surufatinib in China, we're also having a Phase II/III study in first-line pancreatic cancer in combination with PD-1 and chemotherapy. Phase II is fully enrolled and the data readout we're going to showcase later this year. And tazemetostat is the global first-in-class molecule, EZH2 inhibitor. We licensed from Ipsen. We have completed our bridging study and the study -- and the drug was approved earlier, March 2025 by NMPA in the third-line follicular lymphoma. And also, we're making great progress in the second-line lymphoma trial. Also for sovleplenib, our Syk inhibitor through the ESLIM-01study in the second-line immune thrombocytopenia, we have submitted an NDA. As we know, there is a impurity issue we have been addressed. We reached agreement with CDE, really define the intake level and moving forward with the resubmission early next year.

And also our second-line autoimmune disease is warm autoimmune hemolytic anemia study. We already complete the enrollment with the potential readout and NDA next year. Newer pipeline is the second-line FGFR2 inhibitor fanregratinib and also with the potential for NDA this -- later this year. And our dual IDH1 and 2 inhibitor ranosidenib also in the Phase III study in the AML. Here's the fruquintinib with sintilimab combination versus standard of care in China, axitinib or everolimus. The data FRUSICA-2 has been presented at the ESMO Congress through the oral presentation by Professor Zhenhua Liu. Here's the trial design is the fruquintinib plus sintilimab versus the investigator choice of axitinib or everolimus. And the clinical endpoint, primary endpoint is the BIRC review PFS by independent radiology assessment.

And here, it was demonstrated in the primary endpoint by BIRC analysis PFS. fruquintinib plus sintilimab versus comparator really show very robust activity with a median PFS of 22 month versus 6.9 month of the axitinib or everolimus group. And it's highly with a hazard ratio 0.37 and has a very similar results for the investigator assessment. Also in terms of response rate by BIRC review and the investigator review, we can see over doubling of the overall response rate by sintilimab and the fruquintinib combo really showing this activity in this patient group with a very high unmet need. We have seen the 63% reduction in the risk of disease progression by the combo drug, really impressive PFS by central assessment, about 15-month difference. And so it's highly significant, very robust response rate. It's highly clinical meaningful. The NDA is currently under review by CDE. We're expecting approval next year.

Also, we are conducting the Phase II/III first-line pancreatic cancer trial. Surufatinib and the camrelizumab, which is [indiscernible] PD-1 along with the standard of care gemcitabine plus nab-paclitaxel versus gem versus nab-paclitaxel. So the Phase II results will -- has been accepted by the ESMO Asia. So we'll present this top line data in the ESMO Asia meeting in December. On the savolitinib side, the MET -- SAVANNAH study by AZ presented data at ELCC in March in Paris, showing the high response rate of 56% and 55% by the BIRC review. And METex14 skipping patient population, we also presented our confirmatory Phase III study at ELCC and really showing very impressive overall survival for the second-line, 25 months and first-line, 28 months in ELCC. Clearly demonstrate this is one of the longest overall survival has been reported among all the MET inhibitor in METex14 non-small cell lung cancer setting.

SACHI data really provide a future growth. The OSI+SO really showing the clinical robust activity was presented as a oral preliminary presentation at ASCO and the manuscript has been accepted to be published in Lancet. We are looking forward the SAMETA trial in the PRCC, the savolitinib with IMFINZI versus SUTENT. So this trial has been recruited. The readout will be next year. And also AZ lead the SAFFRON study also has reached the enrollment target. And we expect a positive -- we expect the results next year. If positive, this will really be hopeful for our second molecule can go to the global NDA. And in China, for this SANOVO study, first-line OSI+SO MET amplified overexpressed patient enrollment is completed and we are really hoping for the readout later.

On the gastric cancer in MET-amplified patients, we also will have the potential to submit NDA. The next molecule is an EZH2 inhibitor, tazemetostat. It -- we have conducted a bridging study, really showing a very consistent study compared with the global trial, Ipsen trial and really showing a robust complete response rate of about 18% and 63% overall response rate and very high percentage of clinical benefit rate. So the drug has been approved. We are further conducting along with our partner, Ipsen, to conduct a global SYMPHONY-1 trial. And this is the tazemetostat in combination with R square, rituximab and lenalidomide and versus placebo with R square. And we are very happy that China wild-type patient has completed the enrollment. And this global trial will not only move the -- if positive, will not only move the tazemetostat to the second line but also has the potential not only in the mutant patient population but also the wild-type patient. So our partner and Ipsen and HUTCHMED are really working towards the full recruitment for this patient group.

Fanregratinib is the FGFR2 inhibitor. And we have previously agreed with the CDE and using the single-arm registration to -- in order to potentially have their conditional approval in this registration cohort in the 2 week on/1 week off schedule, 87 patients were recruited. And so we are expecting the data readout and if positive, we'll file the NDA this year. Sovleplenib is the Syk inhibitor and we first report our ESLIM-01 result at EHA and really showing a very robust or durable response rate of 48%. And last year, we showed the follow-up long-term study demonstrated overall response of 81% and durable response for 51% and has very fast [ on-site ] to increase the platelet. And also unlike the TPO-RA, which also stimulate the platelet production but also has the opportunity to overshoot.

So TPO-RA has a potential for [indiscernible] thromboembolic events, which in the ESLIM-01 study for sovleplenib, the thrombocytopenia is -- thromboembolic event is not a safety concern. So it has a highly differentiated clinical activity and safety profile. We know we reported earlier this year, right, the -- although the previous NDA was delayed through a impurity issue but we have reached agreement with CDE, really defined the intake level and we are continuing to conduct a stability study, bioequivalence study with this new formulation. Our targeted resubmission is in the first half of next year.

And also, we have completed the enrollment of our Phase III ESLIM-02 trial in wAIHA autoimmune hemolytic anemia and we are potentially with the readout next year and if possible, the submission in China. And the -- here's the Phase I data we have shown in the wAIHA patient population -- in previously treated wAIHA patients, we have demonstrated overall 66% overall response rate and also the 47% the durable response rate and really showing the highly robust activity for the Syk inhibitor, not only in ITP but also in wAIHA patients.

So I gave you an overview of the ATTC platform and also the -- our late-stage pipeline advancement. So to summarize, so for today and beyond, we are really striving for global commercial success. And our partner, Takeda, really showing the fruquintinib global sale first half of this year really increased by 25% to $162 million, showing robust growth. ORPATHYS or savolitinib with our partner, AstraZeneca, we have the potential to really -- if the SAFFRON data is positive, will be our second molecule [indiscernible] potentially registered internationally. And ELUNATE is, fruquintinib is continue to grow with the new indications with the endometrial cancer approval will certainly will help the commercial launch. And also with the new RCC trial, we hope the fruquintinib plus sintilimab in the RCC trial will receive the approval in the next 12 months. And SAFFRON, of course, SAFFRON and SAMETA led by the AZ development will all have Phase III readout next year. And if positive, will potentially strong catalyst for the company.

And surufatinib PDAC in combination with PD-1 and chemotherapy will have the data readout. And again, the FGFR inhibitor, fanregratinib and also the Savo GC in gastric cancer with the MET amplified patient will have -- all have the potential for NDA submission. And more importantly, looking for the future, we are thinking our next-generation technology platform, antibody target therapy conjugate, ATTC profile has a huge potential. And we have multiple selective candidates currently at the -- enter -- will enter the clinic. And the first is already reached the IND clear in the U.S. And also with the company has a strong balance sheet and also relative small market cap, we think our future potential is really have a great opportunity. And along with our robust cash position, certainly, we are continue to looking at in-licensing and out-licensing opportunity. So hopefully, our effort and advancement can be appreciated in the investment road and really leading to long-term growth and generate value for our shareholders.

So with that, I'll just wrap up and opening for questions.

Okay. Thank you, Dr. Shi, for the detailed analysis. [Operator Instructions] The first question comes from Alec Stranahan from Bank of America.

Really great to see progress across the pipeline. I guess first on the ATTC platform, how important is it for you to really drive monotherapy efficacy in your molecular design of your ATTCs versus, I guess, optimizing safety to align it with frontline combo opportunities, especially when we're talking about assets like A251 that go after broadly expressed targets?

Yes. Thank you, Alec. Yes, it's a very good question. So for us, right, of course, the traditional development is really try to see some activity in the late-stage setting. So that's why we enrolled patients with -- previously treated patients. And our belief it is in the target patient population, for example, HER2+ and with the PAM altered or nonaltered patient, we will expect to see the activity. Certainly, we explore multiple cohort in the late-stage setting if we have defined the patient population could have a more robust activity, could certainly lead to the potential accelerated registration approval. But the main difference here for the ATTC, for A251 example, is what we consider is the opportunity to really advance to the frontline. And we have demonstrate multiple model, have synergistic activity with the traditional chemotherapy or standard of care therapy.

And a lot of these toxin-based ADC really have difficulty to combine with other chemotherapy. So that's why we think this is a advantage for us. And also, this is a unique opportunity to really take on this combined U.S.-China trial, right, to really simultaneous development to advance our pipeline because, as you know, the FDA is really encouraged the earlier line development, right, instead of just the frontline setting -- late-line setting because through this project frontrunner activity. So we think even at the -- when we have the dose escalation and even we have this [indiscernible] design with a backfill strategy to expand the dosing. Once we see activity or certain signal, we will have the opportunity to start a combination study and soon to really advance this development because our hope, we have shown this -- the combination, not only with the chemotherapy and some -- even the model with toxin-based ADC also shows synergistic activity.

So the key driver for this ATTC platform is really moving to the early line and to compete with the standard care. In combination with the standard of care versus standard care, we think that will be the future growth driver. And as you know, even the toxin ADC has a lot of efforts to combine with chemo but the data really from the safety profile, discontinuation, combinability really show strong limitation. So we believe that's where we can compete in for the tumor type because this unique profile for this ATTC platform.

Okay. Okay. That makes sense. And I guess one on the frontline PDAC opportunity for surufatinib. I guess, what do you sort of see as the bar for efficacy in the Phase II readout in December in combination? And I guess, how should we be thinking about the activity of surufatinib here versus PD-1 alone, given the control arm only includes gem/nab-paclitaxel?

Yes. So we are looking quite some historical data, right? Because pancreatic cancer is highly fibrotic and is usually considered as a immune desert. So PD-1 plus chemo alone, right, really haven't shown very robust activity. And from our perspective, the surufatinib is not only a VEGF inhibitor, it's also inhibit CSF1R and FGFR, really has a very strong potential through our early study. The initiation is a Professor [indiscernible] trial with the PD-1 and surufatinib combo with different chemo regimen and showing the ORR rate is about -- over 50% and compared with standard of care about 25%. And in particular, the ORR reported at ASCO GI earlier this year, showing the OS benefit is really beyond 12 months, right, about 15 months.

So that's what we think not only for the PS side -- PFS side but OS side, this combination has a unique advantage compared with the chemo alone or chemo plus PD-1 alone. So the bar, we think, right, is if you compare with the gem/paclitaxel and the -- usually the overall survival is very short, like 9 months or so. So I think with over a year OS, with the robust PFS, we think this combination really show pretty impressive opportunity from the early phase data. So again, the data presented will really show how we evaluate the bar. You will see this soon. And that will really define what is the bar we want to overcome to lead to the Phase III.

Next question from Goldman Sachs, Khalil Fenina.

This is Khalil, calling in for Paul Choi. I guess a couple of quick questions from us. One on the earlier-stage ATTC program and one on the later-stage pipeline. I suppose starting with ATTC, you've identified prostate cancer as the second largest commercial opportunity here in the longer term. And just given the emergence of nuclear medicine in the space, I'm just curious like in your view, do you envision perhaps running a study in like Pluvicto experienced patients to see if those types of agents amplify PAM at all? And then the second question is just on ITP. You mentioned looking to further develop it ex China. Just curious what the status was on that.

Yes. Thank you, Khalil. For the prostate cancer, right, because what we think this, the payload targeting PI3K/PIKK has very broad opportunity really against in multiple tumor types. And so we think, at least from a development perspective, we have very many options where to go to. And certainly, we'll probably choose a few tumor type through the company, see what is the late-line setting will -- readout will be and also start a combo study to really get the clinical evidence-driven kind of a development plan, right? Because certainly, in the nuclear medicine, evolving nuclear medicine, certainly, I see the Pluvicto data is quite impressive. And -- but in terms of future development, we probably will have to see how the expansion cohort readout and where the strongest evidence or opportunity will lead us to guide our future development plan.

Certainly, prostate cancer is on the book but we have to look at how the data readout in many tumor types to really make the decision for the early line development in the future. In terms of sovleplenib and so we have quite communication with the CDE because it was submitted and under review because we reported early this year, we certainly have reached the -- mutually agree that the [indiscernible] limit, right, to be acceptable. And in order to accomplish that, we have to kind of change the new formulation. And through this, we're going to work on the BE study and also with the stability testing to really satisfy the requirements. So the targeted resubmission is early next year. And so this is -- we think with this clear agreement guidance, I think we have a path for the sovleplenib in China, not only for the ITP but also with wAIHA when it's readout earlier next year.

So in terms of global development, we believe this newly agreed -- I mean, this agree with the limit actually with the CDE is the most kind of industry standard, including the global FDA, EMA is [ agreedable ] intake limit. So I think that formulation will certainly satisfy the global development for this product for a global potential. So I think that really opened our store. Again, we mentioned we paused the U.S. and EU development just really because of this issue. But now I think we are in a position to really looking at international development. As you can see in the ITP study, at least, for example, the ESLIM-01 data is show -- clearly show a highly durable response rate. And the long-term exposure demonstrate a sustained platelet increase and a durable response compared with all these existing product of -- including a new one, right, the FcRn with the [indiscernible] and all these activity, we think Syk inhibitor really representing a probably best-in-class modality to really in this patient group.

And because ESLIM-01 data is really heavily pretreated patient, they filled all the first line and also the 75% of patients filled the TPO-RA. And so certainly, in the heavily pretreated patient, we can see this most robust ORR really showing this as a opportunity. Certainly, we will reposition and really thinking what is the fast track for the global development. And in parallel, I think we can reengage some of the discussion with the partner and to really leverage this molecule's unique -- because this dual mechanism inhibiting the, engulfing the platelet or red blood cell and also the blocking the B-cell activity. So these are certainly a strong clinical evidence activity. We think this -- with this newly developed formula, it certainly have a pretty good opportunity to be further developed globally and open the door for discussion for future partner. Yes. Also, by the way, we're going to present our long-term, the final ESLIM-01 data at ASH. It has been selected as a oral presentation. So I think it will reignite the interest for sovleplenib.

Next question comes from Jefferies' Clara Dong.

I appreciate putting together this very informative presentation. So 2 from us. So maybe can you broadly just talk about how the programs developed through your ATTC platform will complement your existing commercial and late-stage initiatives and how kind of this integration will support your long-term strategic vision? And how do you prioritize your indication selection for those programs? And then also given the novelty of the ATTC platform, would you be able to share any color in terms of what's the bar for safety you're looking for, for the very first ATTC candidate?

Yes. Thank you, Claire (sic) [ Clara ]. And they -- for ATTC, right, I think just really leverage our traditional HUTCHMED small molecule expertise, right? For target therapy, we really work on the linker and the payload to really have a opportunity to generate this molecule and platform because from antibody selection to the target therapy payload selection really provides some good opportunity. So I think the first wave of development, of course, we are really science-driven, target-driven and thinking where the development will really leading to not only the highest clinical potential proof-of-concept and clinical success but also the development path will synergize with our expertise traditionally, as you can see, is the GI cancer, lung cancer, for example, right? So with the further development and with the antibody, with the target payload selection, really, I think we have many, many opportunity, many different type, which just really cover a very broad range of tumor type.

So the development probably will focus initially in the area we think we have a strong interest to be further developed. And of course, it's data-driven, science-driven but also if it's proven to be successful, right? And so far, you asked about the bar of the safety or so at least from the preclinical data, we really see this platform and overcome some of the traditional limitation for small molecule for systemic exposure because as the example that I show you for A251, right and in the GLP tox study, we don't see this hallmark for the PI3K small molecule inhibitor. And for example, hyperglycemia, myelosuppression or so. So just from preclinical data, we know because this selected target delivery of the ATTC into the tumor cell and the very low exposure of the small molecule payload in the circulation, really demonstrate the safety margin compared with the systemic exposure for small molecule. So we think the safety level really from the preclinical data really show us this is have a substantial increase from the traditional small molecule approach.

And the combination with all the multiple target development, multiple antibody development, we think it really generates a unique platform. So to just give you some color, I think our next wave product, right, after this proof of concept for the first wave molecule, certainly, there are more innovative molecule on the way, including bispecific ATTC and probably more do payload kind of the ATTC also in the research stage. So I think this will represent huge opportunity for our platform. And of course, there are only limited resource. We have to focus on area where we expertise to really develop fast proof of concept. And certainly, with the future potential partnership, we certainly think they can really broaden the indication, broaden the development because these -- all these molecule have potential targeting broader tumor type, high-frequency driver mutation overcome the resistance. So the opportunity is really quite huge from our perspective. So will be the focus of our company's new effort for these globally competitive first-in-class assets.

Our next question from Cavendish, the -- Adam McCarter.

Really interesting. So I guess the first question I have, the safety data for A251 looks really encouraging, as you say, Dr. Shi, particularly the absence of the elevated blood glucose levels. So you mentioned that this may relate to the compounds targeting ability, which is helping to limit systemic toxicity. But could you elaborate on whether you're seeing differential inhibition across AKT isoforms and tumor cells? Some of the tolerability issues seen with earlier pan AKT and PI3K inhibitors have been linked to the AKT2 inhibition. So it would be useful to understand how A251 compares mechanistically in that regard.

Yes. Thank you, Adam. Yes, also very good question. Of course, we're actually looking at these -- all these potential PI3K/AKT pathway inhibition, right? So in short, right, because we do see the free payload release in the plasma is actually quite low. If you calculate from that exposure curve, the free payload itself is actually showing pretty much less than 1,000fold or even higher kind of a differentiation. And pretty much all these free payload concentration we have seen is well below the IC50 level to reach the target inhibition. So that's why we do see the safety profile margin. And also through monitoring, right, is we understand -- is because the dose we select for the tox study, we really monitor the threshold.

So we can see the certain, I would say, on-target kind of the AE profile, it's reversible, it's dose dependent. So that's why we feel this ATTC provide a very safe window for future development. So hopefully, certainly, we hope this will be represented in the human study, right? So really looking for the first-in-human study and how the safety and the activity will pan out. If it is clinically proven, I think they will represent multiple huge opportunity, right, for the next wave of product we are developing.

That's great. And if I could just ask a second question. So you've highlighted that your ATTC platform differs from the standard ADC approaches. Just wondering if you could expand on the competitive landscape here. Are there many others pursuing this targeted therapy payload strategy with similar design principles? Or is your approach relatively unique at this stage?

Yes. I think this -- the field is really evolving very rapidly, right? I think all the scientists really thinking about different way, right? You can -- there are different approach, right? Even you see this -- the most recent example, right, Innovent is linking the immunotherapy with the target -- in the antibody, right? So certainly, I wouldn't say the competitors won't invest or develop in this area. But I think we are also in a very strong position because HUTCHMED is really have a long-standing, right, small molecule expertise. I thought our strength is really in the linker and the payload. And also, we have really working in multiple target therapy development areas. So I think with a deep understanding of biology, coupled with the strong medicinal chemists and new -- newly more innovative novel antibody or bispecific antibody, we think we are in new -- I mean, very strong position to really leading and innovate in this field.

Since there's no more question, this will be the end of this presentation and our R&D Day event. Thank you again for joining us and we wish you a wonderful day. Bye-bye.

Thank you.

[Statements in English on this transcript were spoken by an interpreter present on the live call.]

Hello, everyone. This is David Ng, Head of Investor Relations of HUTCHMED. Thank you for joining HUTCHMED 2025 Interim Result Presentation. Our result and presentation slides have already been posted on our homepage as well as on the Hong Kong Stock Exchange website.

Just a quick moment on the disclaimer. The performance and results of operation of HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results, and actual results may vary materially from those set forth in the forward-looking statements.

So today, we are very glad to have our CEO, Dr. Su; our CFO, Mr. Cheng; our CMO, Dr. Shi; and our Head of Commercial, Mr. Yuan, to go over the results and provide the latest update on our performance and the projects under development. As usual, we will have a Q&A session at the very end [Operator Instructions].

So now let us welcome our Chief Executive Officer and Chief Scientific Officer, Dr. Wei-Guo Su to begin our presentation. Dr. Su?

Thank you, David.

If we go to the next slide. So again, good evening, good morning, everyone. Welcome to the HUTCHMED midyear result conference call. The highlights for the first half 2025. Global commercial success. FRUZAQLA continues to grow first half, up 25% comparing to 2024. ORPATHYS or savolitinib, potentially our second global commercial product. There are filings ongoing based on SAVANNAH in some countries and also, obviously, the global registrational study, SAFFRON study is recruiting. We anticipate completion of recruitment later this year. And of course, ELUNATE in China new indications, endometrial cancer approved early this year and RCC already filed as well.

We do have a lot going on. We expect in the next 12 months, our Phase III first-line non-small cell lung cancer, osimertinib plus savolitinib study called SANOVO [indiscernible] should completing enrollment very, very soon. If anything, I think we're already fully enrolled. SAFFRON, as I mentioned, should also complete recruitment shortly.

Surufatinib Phase II/III study in first-line pancreatic cancer, Phase II readout and a Phase III transition is progressing. Our FGFR inhibitor NDA submission is in preparation, plan to file -- later this year. And the savolitinib SAMETA study for TRCC globally and gastric cancer in China, NDA submissions are also planned. Fruquintinib RCC, as I mentioned, NDA filed early this year and within the next 12 months, we expect approval. The SAFFRON study, of course, the Phase III readout should be sometime first half next year.

Our next-generation innovation, very exciting ATTC programs, the first candidate IND filing coming up very soon in a month or so, and we have more to come later this year. And we are also exploring BD activities for not only our ATTC programs, but other programs as well.

Without further ado, I will just hand it over to the next speaker, our CFO, Johnny Cheng, to give you a financial overview and update. Johnny?

Thank you, Dr. Su.

On Page 6, we can see our balance sheet reflects a very strong cash position, over $1.3 billion in cash resources, which includes proceeds from the partial divestment of our joint venture with Shanghai Pharm. So, these resources will allow us to accelerate global ATTC development and explore potential investment opportunities. Further down the balance sheet, under other noncurrent liabilities we have deferred approximately $18 million of divestment gains as a provision for profit guarantee to the buyers. This will be recognized over the guaranteed period, subject to the joint ventures performance in the next few years.

Turning over to Page 7, our P&L. So overall, the revenue for the first half of 2025 was $278 million, down 10% versus same time last year. Investment in R&D amounted to $72 million, reflecting multiple NDAs under review in China. On the bottom line, we have reported a record high net income of $455 million, mainly contributed by the partial divestment of our joint venture with Shanghai Pharm.

Moving on to the next page, we have adjusted down our full year revenue guidance to between $270 million to $350 million, mainly to reflect a revision for the phasing of certain clinical and commercial milestones and also the delay of savolitinib commercial launch.

I will now pass to our Head of Commercial, George Yuan, to share with us on the commercial performance.

Thanks, Johnny. The first half year of our commercial results is relatively flat. Fruzaqla posted a very strong growth, 25%, offset by a weaker China performance in -- for 3 brands, ELUNATE, SULANDA and ORPATHYS.

Next slide. If we look at Fruzaqla, we note that CRC is the third most common cancer and also the second leading cancer for the fatality worldwide. And with [ indiscernible ] adding to the launch market and also include reimbursement, we see Fruzaqla deliver a very strong solid growth in the first half year, especially Japan with Takeda's strength and know-how in the CRC market as well as the benefit and the value of Fruzaqla in CRC being highly recognized by NICE recommendation. So these product will continue to gain market share and through the expansion of the reimbursement and the new launch countries.

Next slide. The China CRC market become very competitive in the later line. We see more fruquintinib generics and TAS-102 generics launched in the past 12 months. Also, there's uptake of the combo regimen in the third-line beva combo become cross-line treatment become more popular than before. And also, we faced a final push by the fruquintinib before the [ VBP ] . And so we adjust our market strategy, and we gain back some of the share from the Q2 -- this year. And we still believe we are the strong market leader in the third-line CRC, and we will continue to be the market leader in the CRC. And the EMC launch as well as the future RCC approval will further drive our growth.

Next slide, this year, the MET TKI -- the MET market went through a strong turbulence with additional 4 NRDL listed products starting from the year beginning with all of the 4 with the first-line indication. ORPATHYS actually lost some market share in the beginning of the year. But through the middle of this year, we get full approval first line as well as the SACHI approval before the middle of this year. ORPATHYS has been well positioned for this year's NRDL renegotiation. Of course, SACHI is certainly the key differentiator versus others TKIs.

Also, we will strongly leveraged the AstraZeneca's expertise in the lung cancer. The combo treatment will be the first and the best oral dual precision medicine to offer to the lung cancer patients.

Next slide, if we look at the MET market, we also have some kind of headwinds. We see the octreotide generics launched in the market. Also, we saw this year lanreotide gain to the NRDL and multiple nuclear medicine, the PRRT treatment is under clinical development, which is fighting for patient share in the top centers. We do see a short-term hiccup for our business. But if we look at the future, we still believe we are the market leader in the TKI segment, and we have an obligation to gain the market share for the whole segment as well as [surrender] in the NET treatment. The diagnose and the know-how of the treatment is for the NET is still growing, and we believe there's a lot of education opportunity as a leader in this -- in the TKI segment, we will further drive the category. Next, I will hand over our Mike.

Yes. Thank you, George. I'm going to give you an update about our pipeline. So, we have made tremendous progress in our late-stage product development in addition to the global approval of the CRC, fruquintinib also expanding into the new indication in China, such as endometrial cancer and RCC. And our another brand, savolitinib also achieved label expansion approval with multiple new indications in the late-stage development, again, with our partner, AstraZeneca.

As Dr. Su also mentioned, surufatinib is in the late Phase II development with a late phase readout later this year. And our first heme product, tazemetostat has been approved in China with additional new indication development in the follicular lymphoma. Later on, I'll also give you an update on our first Syk inhibitor in sovleplenib for NDA and also the wAIHA development. And our third wave product, ranosidenib and fanregratinib also at a pivotal registration trial stage. All these products will propel our future growth.

Next slide. And this slide also give you a update of our early-stage pipeline advancing or will be entered into the clinical development. First, 760 is our third-generation BTK inhibitor, currently still in the Phase II development in the refractory DLBCL -- and our new Menin inhibitor 506 also entered the clinical development is in the dose escalation stage in the AML.

Also today, I'm going to give you update some of our new class of agent. Dr. Su mentioned ATTC Antibody-Targeted Therapy Conjugate product. 3 early pipeline, A251, A580 and A830 will all enter clinical development later this year and also next year.

Next slide. Here's our update about the ATTC platform. During the last conference call, we disclosed our new platform. And so now we're actually making pretty advanced progress in our first 3 molecule and targeting enter clinic pretty soon. And so I think the ATTC have several key differentiation shown here because we really leverage and maximize the synergy between the target therapy antibody and also our small molecule know-how as a payload and really through the linker optimization to really overcome some of these physical chemical property of small molecule as a payload. And so by doing that, it could have a better efficacy through antibody and small molecule combination will target specific mutation, can overcome drug resistant and potentially support a combination with other target therapy, particularly in the frontline setting and also improve the safety given the low target -- on-target and off-tumor toxicity than the small molecule.

And also, unlike other toxin-based ATTC, it has less myelosuppression and also have a better quality of life and also have a favorable pharmacokinetic profile resulting from antibody-guided delivery to the target sites, improved bioavailability and reduce drug-drug interaction compared to oral small molecule TKI.

Next slide. So mechanistically, the ATTC can target protein required for cancer growth. It has a synergistic effect with the combination with functional antibody and also has the ability to combine with other chemo target therapy or standard of care chemotherapy and which is particularly important in the frontline setting. And also, there are numerous report the chemo-based ADC is working less effectively with the tumors with [indiscernible]. So this will have the opportunity to really establish a better therapeutic window and through the reduction of on-target and off-tumor toxicity. And also it have other -- less other compound-induced toxicities such as liver QT, lung QT, et cetera. So it can be dosed long term with improved safety window and with a reduced systemic toxicity for small molecule. And more generally, the ATTC platform can also be expand to incorporate high molecular weight drug payload. So this is actually a platform to have multiple opportunity.

Next slide. So this is the design of our first ATTC candidate, A251. So on the antibody side, it use a clinically proven, well-established humanized IgG1 antibody and with a small molecule payload with a drug-to-antibody ratio of 4. For the proof of concept of this platform, the antigen we selected is expressed in multiple tumor types and the antibody is internalized favorably. And on the payload side, it really leverage our small molecule expertise and with a highly potent against kinase family [indiscernible] alteration and has the potential to synergize with the antibody to overcome resistance and improve the efficacy.

We also show you some of the bystander effect to kill the antigen negative cells. And also on the linker side, it has a pretty stable in the plasma and will be cleared by the protein highly expressed in the cancer cells, so have a very precise target delivery in the tumor cells.

Next slide. And this slide shows some of the preclinical data for A251. In the panel of the tumor cells, we actually see a very potent activity with a sub-nanomolar range of IC50 for tumor cell lines with high antigen expression. And in the middle figure, it shows the bystander effect. For antigen expressed tumor cells, it has pretty good tumor killing, but low or no expressed antigen, right? The A251 has no antitumor activity. But if you co-culture the antigen positive and negative cells, it actually have activity to kill both the negative and the positive cells. So it really demonstrates the bystander effect. And also it preserve the ATTC activity as same as the naked antigen antibody showing on the right-hand figure here.

Next slide. And this is a proof of concept -- preclinical proof of concept for our- A251. The target antibody is linked to a target therapy payload with a special linker. And the left figure show here is the target one antibody showing in green and the small molecule payload with showing red here with a biweekly dosing. And it shows tumor growth inhibition. And also the single dose target 1 and ADC shows a robust antitumor activity compared with the antibody alone or the small molecule payload alone or the combination of both payload and antibody. So this is very important proof of concept showing a single-dose ATTC deliver a sustained tumor inhibition over a 14-day period of time and show good tolerability because on the right-hand side, we can see the payload itself or payload plus antibody, although have the tumor effect, but they also reduce the body weight, but the A251 itself dose at the 30 milligram per kilogram has no weight loss. So it's very important to show not only induce tumor regression, but also have a very good safety profile.

Next slide. And also, the A251 also show very good synergistic activity with the standard chemotherapy. The left panel here is the tumor xenograft model. The combo with chemo show a synergistic effect. And also on the right-hand side, we have seen the tumor cell line study also show the chemotherapy plus A251 have synergistic activity. So this is quite different from the other toxin-based ADC because in all the clinical development setting, you can see most of the ADC toxin-based ADC cannot actually combine with the standard of care because the toxicity.

Okay. Next slide. Also, I'm going to highlight some of the progress on our key asset, savolitinib and both in the global and the China development really going to drive the future growth. So at the ELCC 2025, we have reported the data [ASCO] reported data for SAVANNAH study and showing the durable response -- overall response rate. And in the same conference, we also showed the -- our savolitinib in MET Exon 14 skipping non-small cell lung cancer also show a very good response rate and also the sustained overall survival. So this also lead to our approval, not only get a full approval for late-line MET Exon 14 non-small cell lung cancer indication, but also expand the first-line indication.

Very importantly, George also mentioned about our second-line EGFR TKI refractory patients, ORPATHYS plus osimertinib in MET amplified patient. This one, we achieved the NMPA approval in the June and also has been selected in the ASCO presentation during the annual ASCO meeting. Dr. Su mentioned our PRCC, the SAMETA trial will finish -- also finish recruitment and the readout for this trial will be early next year. And for the China side, we also achieved the recruitment for the SANOVO first-line trial. And also, we are trying to finish the SAFFRON trial recruitment this year. And the gastric cancer in MET-amplified patients also are preparing NDA for later this year.

Next slide. This is also showing the key results for SACHI trial. And in the overall intent-to-treat patient population, the PFS osi plus savolitinib reached a hazard ratio of 0.34 and the PFS improvement versus chemo from 4.5 to 8.2 month. And also regardless the first, second-generation TKI treatment or prior third-line TKI progressed patients, the hazard ratio is very consistent. And in particular, for third-generation TKI refractory patients, as you can see, the control chemo arm have only have a PFS 3 months and the savo plus osi reached the PFS almost 7 months. And also the response rate, disease control rate and durability of response also has been extended by osi plus savo combination.

Next slide. And interestingly, we also observed the publication for amivantamab in the MARIPOSA-2 trial, as you recall, the AMI plus chemo versus chemo trial, they also have a biomarker subgroup analysis. MET-amplified patients only identify about 40% of the patients in the MARIPOSA-2 trial. And unlike our study for SACHI, we observed about 50 --30% of the MET amplification by FISH analysis. And so in the patient population, as you can see, the chemo arm, actually both trials, the MARIPOSA-2 and the SACHI trial are very consistent. Remember, these patient have MET amplification, progressed on the prior third-generation TKI and amivantamab trial showing the PFS of 3.1 months, but their improvement is only to 4.4 months PFS with a hazard ratio of 0.51.

So the patient population in this population, what we can conclude, just like the SACHI MET-amplified patients have a very poor prognosis, their PFS only 3 months. But savolitinib plus osi reached the PFS almost 7 months with a hazard ratio of 0.32. So this is quite significant difference. We believe in the biomarker selected patient population, -- savo plus osi really demonstrate superior activity, really addressing these patients with poor prognosis. And also, both the SAVANNAH and SACHI trial demonstrate the combo has a very effective effect in the patient with the baseline brain metastases. So these are the key difference between the osi plus savo compared with other study because this is the only biomarker selected patient population and also with the only chemo-free regimen. So we believe this will have a very substantial usage in the clinical setting.

Yes. Next slide. And SACHI approval, I also want to mention it enable us to go through the NRDL negotiation this year. And also, we presented our savolitinib MET exon 14 trial at the ELCC. And we have observed very substantial improvement of OS. So the patients with the prior treated with patients with OS of 25 months and the patient with the frontline setting, the treatment-naive patients, the OS with a long follow-up have OS with 28 months and the upper level has still not been reached. So among all the MET TKI, the savolitinib actually demonstrated the longest overall survival repeated so far. So we are very excited about this data.

Next slide. And also, fruquintinib has been extending into the other indications. So we already got early approval for the endometrial trial. We have the overall response rate of 35% and also the median PFS reached 9.5 months. And we are also going to present our Phase III FRUTIGA 2 trial at the upcoming ESMO later this year and showcase the activity has been chosen as a meaningful oral presentation. So we'll highlight the data. And the NDA has already been accepted and under review at the MMPI.

Next slide. Our first hematological product, tazemetostat also get the third-line follicular lymphoma approval. It showed a high consistency with the global trial. And so at EHA this year, we showed the patient in the third-line follicular lymphoma with IRC over response rate of 63.6% and investor assessed ORR with 68%. So it's very consistent with the global trial leading to the approval in the U.S. and Japan.

Next slide. Surufatinib is our combination study in the pancreatic cancer is going very well. Pancreatic cancer is a highly deadly disease. It have a 5-year survival rate of less than 13%. In general, the PDAC is a cold tumor -- immune cold tumor and not responsive very well with the immune therapy. From our preclinical work and IT study, we actually demonstrate surufatinib as a VEGF inhibitor not only inhibited the VEGF FGFR pathway, but the CSF-1R inhibitor pathway also has an immunomodulating function. So this is a Phase II/III trial currently ongoing in combination camrelizumab, PD-1 and the chemotherapy for the treatment naive PHC. So this will -- at the ASCO 2025, the investigator initiated trial also showed this suru plus camrelizumab with chemotherapy in the first line demonstrated ORR of 51% versus 24% of chemo. And also there is a significant improvement of the PFS. So the Phase II portion of this trial is going to read out later this year. What will trigger -- if the results is good, will trigger the decision making to the Phase III portion of the trial.

Next slide. Also, I'm going to give you an update about the ESLIM-01 study. So we presented the data at EHA last year, demonstrated a robust overall response rate of 71% and the durable response 48%. So because the dual mechanism not only inhibited the macrophage digestion, but also stimulating that inhibit the B cell production. So the dual mechanism of SYK inhibition really provide advantage, particularly in patients who are refractory to TPO/TPO-RA treatment.

During the review of course, as you recall, we submitted NDA and MMPA stimulated a lower [indiscernible] limit. So this requires further CMC validation and stability test. So we target a resubmit with the additional data in the first half next year 2026 and with additional rolling data will be next -- later part of the next year. So here is the update of our sovleplenib in the ITP NDA status.

And next slide. And we also have another trial in warm autoimmune hemolytic anemia. The Phase III trial, we have shown previously that sovleplenib reached an overall response rate of 66% and the durable response of 77% because the wAIHA is very deadly disease and no target therapy has been approved. So it represent a high unmet need. So we are very excited that Phase III registration trial has already completed recruitment and with the data readout next year.

So I think we make a very strong progress in the R&D, and we're really hoping our R&D team with our novel ATTC platform will develop new treatment modality for the new development and our late-stage pipeline will advance and propel for future growth.

And so with that, I'll turn to Dr. Su.

Thank you, Mike, and also thank all speakers for the update. Before we get on to the Q&A, I just want to highlight and give you a sum up. So in the first half of 2025, we completed SHPL partial divestment with the proceeding of over USD 600 million. We also worked on 2 major products, savolitinib and fruquintinib in an effort to expand their indications. Savolitinib, we achieved -- we obtained SACHI approval in second-line EGFR mutant non-small cell lung cancer with MET amplification. We anticipate following the treatment with third-generation EGFR TKI, about 1/3 of patients will develop resistance due to MET amplification. So this combination -- the approval of this combination, savolitinib plus osimertinib offers a treatment potential for these patients.

And MET amplification, as we know, is a driver and patients and these patients do very poorly on standard chemo. And this combination by precisely targeting the 2 drivers, EGFR mutation and MET amplification demonstrated very strong clinical benefits and also chemo-free.

And additional trials are ongoing, including the first-line EGFR mutant non-small cell lung cancer with MET overexpression in China called SANOVO study as well as the global Phase III study in second-line EGFR mutant non-small cell lung cancer called SAFFRON study. So we look forward to data readout of these trials. We believe MET activation plays a major role in driving cancer growth and proliferation.

In addition to lung cancer, as Mike pointed out, we also anticipate NDA submission for savolitinib in China in gastric cancer. And we also expect data to read out in the global TRCC study in combination with IMFINZI. Fruquintinib, we obtained approval in second-line endometrial cancer early this year, and we filed for RCC. So, these additional indications will continue to drive the commercial performance of fruquintinib in China. Outside China, FRUZAQLA continues to grow, delivered 25% growth in the first half. And we expect launches of this innovative product in other countries around the world in coming months. So the launches -- these launches will continue to drive the growth of FRUZAQLA outside China.

So midterm, strategically, we are exploring how we can leverage our cash to accelerate growth, both in commercialization and potentially R&D portfolio as well. So, looking for opportunities to acquire products or commercial products or pipeline candidates. And of course, we are highly focused on our ATTC platforms, very innovative, globally first-in-class molecules. Really, I look forward to the first molecule initiating clinical trial later this year and with more to follow.

Longer term, we need to -- if ATTCs reach clinical proof of concept as demonstrated in preclinical setting, we expect these ATTCs to positioning us for the long-term future growth. These programs will -- as you know, right, will have potential to be positioned in earlier lines, particularly front lines in combination with chemos, in combination with IOs and in combination with targeted therapies. So we expect that these platforms will deliver multiple, multiple products in the future for us.

Next slide. I think this -- you've seen this before. We remain on course. We are committed to profitability, and we look to the future with our next wave of innovation. Thank you, and thank you very much. I think we are now open for questions. David, you want.

Thank you, Dr. Su. So we are now open for questions. [Operator Instructions] So for the first question, can we have Matthew Yan from CLSA.

I've got 3 questions. First is regarding our very exciting ATTC platform. I wonder, is it -- am I right that we will likely to see what drug targets it is in the second half this year? Firstly, regarding A251 and also the development strategy, it seems that -- am I right that you will go directly to the frontline combo chemo standard of care, right? So this is the first question regarding ATTC.

And second is about -- still about the performance and the sales decline because I think you mentioned in your report that there's some reasons related to the transitional effects of the change of sales team and marketing strategy. Can you get more elaboration on this? And this is my second question.

Third question is regarding the SYK inhibitor Sovleplenib because my original expectation is that to have finished the instability test by end of this year and received NDA approval. So what's the new message from CDE regarding this new change of new submission required next year? Yes. That's all.

Okay. Thank you very much, Matthew, for your questions. I briefly touch on your questions and maybe Mike can chime in later. So regarding ATTC targets, the plan is to -- for A251, which IND submission expected in September, early September, just about a month from now. We expect to -- our plan is to disclose the structure of the antibody and the payload at the upcoming EORTC conference. So, you will see -- you will have all the information, all the preclinical development or preclinical data at EORTC.

Yes, development strategy, clearly, I think they have -- these molecules are very different from chemos. They will have very different from chemo or toxin-based ADCs. They will have very different safety profile. And we expect that these molecules can be -- will be able to be combined with a variety of therapies, as I mentioned, including chemo, SoC or IO or even other targeted therapies. So, the development strategy for these molecules will obviously look for signals in the early development. Certainly, they have potential to target tumors with either the genetic aberration or genetic alteration, which our payload targets or high overexpression and so forth as a monotherapy. However, that might be a strategy for rapid biomarker selected pathway for registration.

But much greater potential is in combination in first line in combination with chemo IO or even other targeted therapies targeting all comers without even genetic alterations. And we will explain the rationale at the EORTC conference. So that's about ATTC sales decline.

Team transition certainly had some impact, but a lot more than that. As you know, the anticorruption trial -- anticorruption activity has been going on in China for some time. So compliance is now becoming more and more important. Physicians are fully aware of compliance issues. So there is a practice change in the field or in hospitals. So there's certainly much less or much more careful off-label usage prescribed by the doctors. And so that certainly will shrink the off-label contribution to the total sales. So team is in transition. I think now we are over with it.

The off-label usage dropped but now stabilized. As a matter of fact, first quarter was bottomed out and the second quarter start to grow. We are pretty much back to where we would expect in June and July. So we are very optimistic in the second half, the momentum will continue and will perform to our expectations. So we believe the sales decline in China is transitory, and we are already seeing a recovery, and we are quite optimistic about second half.

Your last question about SYK. So it went through a lot of discussion -- we went through a lot of discussions with CDE on this particular impurity and how we address it, both in terms of using tox studies to qualify the level and additional CMC studies to bring it all the way down to a minimum or to below the target or allow the target level.

So the activities went on in these 2 areas in parallel. And recent communication with CDE, they guided us to focus on CMC. And now we are full speed ahead in the CMC area, where we have to complete the PPQ batches, accumulate the stability data, but we expect to have the data available for initial submission March or April next year and with additional or longer-term stability data to be rolled in since the program is under breakthrough therapy designation in China. So that's where things are. I know it's -- we are all disappointed of the delay. But at least now we have clarity, we can drive with our activities.

I also want to mention about potential out-licensing outside China. This program, as you know, because of these issues, we pretty much stopped the outside China clinical development, even though U.S. FDA was okay with the level of the impurity and allowed us to proceed, but we felt we wanted to explore ways to sort this out. And I think this force issues in China forced us to look into other ways.

So I think we are -- we potentially have a strategy to go forward with -- in the U.S. with a new chemical entity with full patent life. So, I think it will make a lot of sense to switch the molecule outside China completely and with a much longer LOE for the product, but potentially it could be a very short development time line because of the known target-- known. And so I think outside China, it could actually present a very attractive out-licensing opportunity once we finish some clinical -- early clinical development. At least now we think it's a great target for these indications. It's probably the best in ITP and why we have done so far, and it could be potentially useful for other indications as well.

So I think this -- with regard to ATTC and SYK, maybe, Mike, if you have anything to chime in.

Yes. So thanks, Dr. Su. I just want to mention that for the clinical development side, I think we're very excited about this 251 development. And what we're trying to do is really the global development simultaneously with the U.S.-China development because really not only leverage our synergy, but also take advantage of some of the regulatory approach, particularly in the United States. The FDA is really kind of encouraged for -- through this project frontrunner, right, you can actually start the combination in earlier line setting much sooner compared with actually the CDE. So I think this is a part of the development strategy we're going to undertake.

Even when we have the dose escalation, define the dose, we could actually move to the frontline combination earlier. So that will be the key for our development strategy. And we think also, right, you talk about the target and we are planning to close at a future scientific conference later this year. But I think the most important, like I mentioned, our antibody part selection is a well-known target and have a well-established drug in the clinic. But the payload is really the innovation part. And we think our target therapy payload with the linker will be developed really leverage our in-house small molecule expertise can really deliver a lot of potential first-in-class molecule. If this -- if it is a clinical proof of concept is reached, this will be a very robust platform for a lot of new generation molecule to come, yes. So I don't think I have too much to add on the SYK part, the SYK inhibitor, yes. So thank you.

Our next question is from Chen Chen of UBS.

We can't hear. Maybe we'll come back to Chen Chen.

Let's take the next question first. Paul Choi of Goldman Sachs.

Congratulations on the progress. I want to maybe just address the commercial side a bit first. And Dr. Su, you talked about your confidence in the second half recovery. But I wanted to maybe just ask how you're thinking about potential economic sensitivity here affecting end demand in your -- for oncology products in the China market and just sort of what your thoughts are on sensitivity to the economic -- broader economic situation?

And then following up on your comments on the Syk inhibitor and partnering potentially for next generation or follow-on molecule here. Can you maybe just comment on how -- what your timing you think could be for initial entry into the clinic there? I know that's contingent upon a partner, but just sort of what potential time frame you're thinking about there, that would be helpful.

Thank you, Paul. On the commercial --China commercial, as you know, it's been a bit turbulent because of the anticorruption and compliance requirements and also for HUTCHMED in particular, obviously, the team -- the commercial team has gone through a lot of changes as well. Overall, I think the market remains there. Competition may be up, as George pointed out, particularly in CRC -- but if anything, actually, the on-label CRC, we actually saw growth over last year, first half of last year for fruquintinib as well as for surufatinib in neuroendocrine tumors.

So I think what we need to -- I think George's team is now sorted out the marketing strategy, and it's working. And I think we just need to take -- to adapt the team needs to adapt to the marketing-driven strategy and help physicians understand our products and also to help patients, obviously.

I think I obviously expressed optimism for the second half, and that's built on the strong performance or strong recovery of these products in China in the last -- in the past 3 months. So it's been challenging. We just want to be transparent, but we are seeing good momentum at the moment, and I believe that the momentum will continue in the second half. The demand obviously is there.

On the SYK, yes, this is going to be a very interesting approach. I think I hope we can talk more about it. It will be very rapid. I -- we expect the new entity will be in clinic or IND submission maybe second quarter next year. So hopefully, in the clinic before end of second quarter. And most important is that this is going to be a -- we believe it's going to be a very rapid clinical development. Mike sometime will be able to share with all of you. And clearly with high probability of success because this is a known target, and we have a lot of data to support. So, the probability of success should be very high. So, I think, yes, by the time we are ready to go into clinic, hopefully, we have a partner to either codevelop or license, yes.

We just have one last question because of time. We'll try UBS Chen Chen once more time.

My first question is on tariff. And earlier this week, Trump said that pharma tariff is going to be imposed starting from small next week and then up to 250% ultimately. So can management please comment on the impact of your fruquintinib sales in the U.S.? And my second question is for your savolitinib, when can we expect its NDA submission in third-line gastric cancer in China? And also for your EZH2, well, will you consider like NRDL negotiation or commercial insurance drug list this year?

Okay. Thank you for the questions. tariffs, to be honest, we don't have any idea. But given the exporting or the manufacturing cost for the fruquintinib is relatively low. So to be honest, I don't have any idea about the impact. I'm sure it's going to be higher. They have to pay something have to pay the tariffs. But I think the -- personally, I think the impact won't be that much. But until we actually understand the details, I think it's very difficult to estimate.

Your second question on GC for savolitinib NDA filing is planned later this year, likely end of this year. This is for late-stage gastric cancer with MET amplification. EZH2 product, TAZVERIK, of course, we are preparing for NRDL discussion later this year. And obviously, this is a very different product. At the moment, it's still imported drug. The cost is higher. So -- and the patient population it serves the first indication we got approved for is third-line follicular cancer, follicular lymphoma, which is a relatively rare form of lymphoma. So overall, I think we have a lot to talk about when we go up to the -- we engage with NRDL. But yes, that's our plan at the moment.

Sorry, we ran over time a little bit, but -- and I noticed there may be some questions still outstanding. So do feel free to reach out to us, and we will try to answer your questions maybe offline. So thank you, everyone, for supporting us and listening to the call. Thank you, Dr. Su, Dr. Shi, Johnny and George for attending the call. And that's all for the call. Thank you.

Thank you.

Thank you all.

Okay. We'll continue with the next session. My name is Paul Choi, and I cover the biotechnology sector here at the firm. Our next panel is with HUTCHMED. We're joined to my immediate left, Michael Shi, CMO; and to my far left, David Ng with IR. What we'll do maybe is give Michael and David maybe just a minute or 2 to sort of give a quick overview of HUTCHMED, before we jump into questions, and then we'll go with that.

Sounds good. David?

Yes. So let me do a quick introduction. So we are HUTCHMED. We're a small molecule, innovative drug company based off China. We have already 4 drugs commercialized in China. And of the 4, one of those 4, we actually also get the FDA and the EMA approval and launch already. We have global sales of about $290 million from this product called fruquintinib, which is a VEGFR inhibitor for colorectal cancer. And we do have a second one upcoming.

It's currently in a Phase III trial. It's a c-MET inhibitor for lung cancer. We partnered with AstraZeneca. So fully maybe 2 years' time, we will have our second drug being able to go overseas. Apart from this, what we call the bread and butter of our operation, we do have a next technology or next-generation technology platform called ATTC, which I'm sure that Dr. Shi will elaborate into in a while. We have a very strong balance sheet, over $1 billion in cash, profitable last 2 years and we target to remain financially self-sufficient in the upcoming years.

Okay. Great. Thank you for that. Maybe let's start with sort of the big picture. And I guess it's no secret or it's a fairly obvious thing to say that U.S. and China are having a little bit of diplomatic tension here. So -- but this is something that's out of your control as a biotech company. And so maybe to the degree you can quantify it or as you think about it, how does this sort of macro consideration affect you as a company?

So I guess for the overall macro picture, of course, it's very unpredictable. So we can only try to do our best. I think one thing that we decided about 2.5 years ago is for overseas market, we decided to out-license. So while we do have the capability, the scientific and clinical capability to push through to the very last stage before approval, we decided at that time due to what you mentioned, geopolitical risk as well as also the capital market uncertainty that we out-licensed our product.

So in retrospect, it was a very good decision in the sense that we do get the upfront payment. At that time, the upfront payment accounted for almost half of our balance sheet. At the same time, we got the mid-double-digit royalty from our partner, Takeda, which have been doing a fantastic job in launching the drug, and we continue to pursue this strategy.

So I know people will worry about different things, including tariffs and things like that. But in this instance, we -- the cost that we supply to Takeda is like a very small single digit of the ultimate selling price. So even if tariff is being applied, it's a very, very small number or percentage of the ultimate sales of the product.

Now of course, we remain very vigilant of any latest development. But so far, we have to say that the impact has been relatively minimal on our business, and we continue to pursue this out-licensing strategy for the overseas market. Whereas for domestic China, we do everything by ourselves, manufacturing and marketing and clinical development. So this is continuing to be our business model.

Okay. Great. Maybe staying on the topic of Takeda and your partnership there. To your earlier comment, the launch to date of fruquintinib called FRUZAQLA here in the U.S. market has been going pretty well. And so you talked about your earlier partnership with AstraZeneca, but maybe at a high level and a strategic level in terms of markets outside of China, how do you think about continuing to develop partnerships or expanding on your current partnerships going forward here?

I think we continue to -- and we will work -- continue to work hard to attract overseas partnership. And I think the gist of it is we do need to have good product and then good clinical data to support it. So I think definitely in the history that's something that really defined HUTCHMED. We -- our partnership, for example, with AstraZeneca was dropped 13, 14 years ago when the product is just about to enter clinical trial.

And the data that you have just seen coming out from this product just like 2 weeks ago from ASCO is very impressive. So I think there's a very strong case for us to secure even more partnership down the road for our future products. And again, like the thing definitely is on the top of our mind is the ATTC program which is about to enter into human trial later this year. This is definitely a program that we will continue to discuss with potential partners, maybe when the data start to come out in the next 2 years. And again, the key thing is that we want to make sure that it's good quality data and good quality products to secure multinational pharmaceutical partner.

Maybe just to add on to David's point, right, FRUZAQLA, it's a very good experience, right? Our partner Takeda has a very strong base in medical commercial setting in the U.S., in EU and Japan, right? So from the product launch perspective, they have a good penetration with the community oncology. Oncologists here in the U.S. and also just the growth in Japan is pretty impressive. So they have a massive experience. So which we don't have the commercial end to accomplish. So it's been very good so far.

Yes. I want to come back to your point, David, in a little bit on the data you presented at ASCO, which I agree was very impressive in the context of the post-TAGRISSO EGFR landscape. But maybe just sticking with FRUZAQLA here in the U.S., you have an approval here for previously traded recurrent CRC, which Takeda is marketing here. But can you maybe talk a little bit about what is in the clinic in terms of potential life cycle management plans for this molecule and just thinking about how you might expand the opportunity set beyond CRC?

So maybe I'll add on to the point because in China, we -- because the earlier development, we have pretty good experience for life cycle indication. So we just got approval for fruquintinib plus sintilimab in the second-line endometrial cancer earlier this year. And also, we have recently announced the top line results for second-line RCC also fruquintinib plus sintilimab versus axitinib and everolimus in the second-line RCC.

So we're going to present the data in a later conference and the NDA has been submitted and it has just been accessed by NMPA a few days ago. And for our partnership with Takeda, initially, we focus on some of the indications where we can generate clinical evidence, for example, in CRC, gastric cancer in certain areas. And certainly, our partner Takeda is continue to evaluate the life cycle we have taken the knowledge we have generated in China position fruquintinib FRUZAQLA's life cycle indication globally.

Okay. Great, you touched upon a number of opportunities, Michael, in China, one of which I think the most interesting and the largest probably would be the RCC opportunity just from an incident sort of mathematical basis here.

But can you maybe just remind us in terms of the China market right now? Is there a utilization of PD-1 plus TKI combinations? I think typically in the U.S., people think of Opdivo plus nivolumab plus cabozantinib or pembrolizumab plus another agent there? And just kind of what is the landscape like in China for you as -- for your sintilimab plus fruquintinib combination?

Yes. So this is actually the indication if it is approved. It will be the only PD-1 plus VEGF in the second-line setting. So I think the market is actually -- could be very, very good because if you think about the scale, although we haven't presented data yet, but just the Phase II data has been presented at ASCO 2023. We actually show 60% of overall response rate and a pretty long progression-free survival, 16 months in that particular setting.

So this is -- we think this is -- unlike CRC, you have several months PFS, but this is actually a very long duration, clearly show fruquintinib has a differentiated safety to combine with other molecule. In the larger context in China, the dominant first-line therapy is still VEGF inhibitor. Although there are some -- you'll see -- start to see the combination of PD-1, VEGF show up in the first-line setting. But we think in the market potential with the unique second-line setting with the only VEGF and PD-1 will have a continued opportunity to penetrate the market.

Okay. Great. Maybe sticking with the performance of ELUNATE in China, fruquintinib in China. Can you maybe talk us a little bit about what's the competitive dynamic like in terms of that particular product there? And how does your relatively recent label expansion in endometrial cancer potentially helped to offset some of the competitive dynamics where I think you guys are first to get that indication?

Yes. So definitely, in China, things get competitive very quickly, as you can imagine. Of course, in the colorectal cancer landscape, our competitors start to have some generic substitutes in China. Now of course, our patent still has a couple of years of runway, but then we start to still feel increasing competition for the colorectal cancer setting.

Now having said that, the endometrial cancer new indication is a good add-on to try to resume the growth rate. Now last year, we have -- we are at around single-digit growth rate for fruquintinib in China. And of course, given credit that is already the fifth year, it is on the market. But coming this year, we have endometrial cancer which, of course, has almost 2x the duration of treatment than colorectal cancer. And as Mike had mentioned, the kidney cancer indication that we are now under review, if it gets approved next year, that will be another nice add-on. And then for renal cell carcinoma, it's even longer duration of treatment. So even though the number of patients may not be as large as colorectal cancer, but the duration of treatment probably much more than offset that.

And I guess the other thing that a lot of people worry about the Chinese market is the pricing. With the new indication severely discount the price again. We don't think that is the case. I think with the new or the latest trend of the policy, additional indication, there may be still a little bit discount, but it's not going to be that severe. So we think that these 2 new indications can help to sustain the growth of fruquintinib in China in the next 3 to 5 years.

Yes. Even for fruquintinib, it's been on the market for third-line colorectal cancer for a longer time, but it's still generating continued support and evidence, right? And so I think from a physician perspective, getting fruquintinib approved globally also really impressed a lot of these physician treatment patterns because as a single agent, have very good tolerability, duration on treatment. So continue our medical team and our commercial team will be able to continue to keep the dominating market share.

Okay. Maybe just briefly, you also talked about your recent EMA approval there as well. And just kind of -- like what is the utilization, I guess, in Europe then to date? And can you give us a little bit of flavor as to what's been happening there?

Yes. So I think we get first reimbursed in the Spain, right? And in Takeda is really putting effort in the EU to get the reimbursement across country, in U.K., in Germany or so. So the uptake has been strong. And from their producing perspective, getting reimbursement is the focus. And certainly, this is the new molecule coming to the market is certainly with the U.S., Japan approval generated a strong interest. So they still start to increase, yes.

Okay. Great. I want to maybe switch gears a little bit and come back to a subject you brought up earlier, David, which is your recent savolitinib data presented at ASCO. Could you maybe sort of summarize what we saw between the various data sets as there's probably mostly a focus on the Tagrisso progressors, but just maybe summarize for us the data you presented at ASCO and then we can go on from there.

Yes. So SACHI is the Phase III randomized trial across China in the Phase III setting, right? These are the patients who progress on first-line EGFR TKI, including first, second generation and third generation in EGFR TKI. About 35% of patients actually progress on Tagrisso or third-generation EGFR TKI.

So this is the all oral combo, savolitinib plus versus chemotherapy in MET amplified patients. So this -- just science perspective, it is a clear driver for EGFR resistance setting, about 1/3 of the patient population have the MET amplification. So we have this combination savol plus osi versus chemotherapy. So at the time, for the first interim analysis, about 66% information fraction achieved, we have randomized 211 patients. We have clearly shown the clinical benefit, right? The IDMC recommend early stop the trial due to efficacy. We have seen very strong clinical data. The PFS for the controlled chemo arm is 4.5 months. Savol plus osi has achieved 8.2 months PFS, which has a ratio 0.34. So it's highly significant with very significant p-value.

We believe this is practice changing clinical data clearly show in the MET amplified patients. This is a strong clinical data regardless of the first, second or third-generation EGFR TKI. So we believe this is going to be -- I mean, we already filed the NDA in China under priority review. Hopefully, we can get the approved second part of the year.

One, to bring into the context about the global setting, AstraZeneca is running the Phase III SAFFRON trial. And also last -- I mean, ELCC in March, they present the Phase II SAVANNAH trial, which is a similar setting not only include the MET amplification, but also with the MET overexpression patients. They achieved a 7.5 months PFS overall response rate, 55%. So it's highly consistent with SACHI data.

This is going to be a very significant development, not only for HUTCHMED in China, but also AZ with the registration trial ongoing. Hopefully, they can develop -- recruit the patient later this year and the top line readout will be sometime next year. That's going to be a significant value driver for this molecule in the global and the China setting.

Yes. I want to go into the SACHI data. The number you gave of 8-something months is the blended average between patients on first- and second-generation TKIs versus third-generation TKIs. And so you actually saw a higher response -- or a better PFS in the patients who were treated with first- and second-generation drugs, if I recall correctly. So it was even better there.

And then you mentioned that the SAVANNAH data in terms of the global cohort versus the China-only cohort SACHI is pretty comparable on average. And so I guess, one of the things that stood out to me was the discussions comment at ASCO that this is potentially a new standard of care for this population, as you said, likely practice changing.

But we also saw over the weekend some other EGFR treatment experience data from the HARMONi-A study, which was almost briefly discussed during the ASCO panel. It's not exactly the same population. It's not MET amplified or MET overexpressers, but can you maybe help us contextualize, again, what population you guys are looking at versus some of the other EGFR combination studies?

Yes. Thank you, Paul. This is actually a very good question, a very important one because for the savol plus osi combo is the only oral combo and the biomarker selected patient population because amivantamab MARIPOSA-2, HARMONi also, these are unselected patient population.

What we observe, I mean, just compare apple-to-apple for the post third line generation -- a third-generation EGFR TKI resistance, that's really representing the global products. We have 1/3 of the patients in the SACHI trial, also fit in that category. What we observed is the PFS in chemo control arm -- remember, these are MET amplified patients with the fresh biopsy of the progression. These patients actually performed very badly because the overall PFS is only 3 months.

And in this patient population, savol plus osi achieved 6.9 months PFS. Again, the hazard ratio, it's very significant, 0.32. And also very interest -- to your point, we also observed MARIPOSA-2 to publish their biomarker data in the ASCO -- same ASCO setting, it's very interesting because the control arm for MARIPOSA-2 is very similar to our SACHI third generation EGFR TKI with the PFS 3.1 for the chemo arm, similar to our chemo arm, but the amivantamab plus chemo, the PFS is only 4.4 months which is not that significant.

You actually start to wonder, right? Because these are poor prognosis, MET-driven disease. We're actually surprised -- actually amivantamab didn't perform that well for the SACHI data tells us the combo with the EGFR-TKI and the MET inhibitor demonstrate the most significant response in this patient population.

So we think moving forward, in a biomarker selected patient population, the MET inhibitor plus EGFR TKI is going to be more efficient, or more efficacious treatment regimen for a patient and this physician to select the treatment.

And maybe just contextualizing against the biospecific HARMONi data that came out over the weekend. We don't have all the details yet, right? But just maybe high-level thoughts there?

Right. So the HARMONi data what they report is the -- they have to achieve PFS benefit, right, similar like the China trial, but the OS is towards the trend, but it really demonstrate the OS benefit. So also contextualize about this treatment for the SACHI trial will be run is actually the patient, once they progress on the chemotherapy, they will allow to cross over the MET TKI. So in the SACHI trial, over 55% of the patient actually cross over to the MET inhibitor.

What we observe is also there's an OS trend increase with 5 months over improvement although in most of the patients cross over the EGFR TKI in this MET-driven patient population, we think demonstrate OS benefit is actually -- is not easy, but we actually start to see that separation. At this point, the OS maturity rate is only 40% for SACHI.

So less than half so far?

Yes. So we can continue to follow up on the OS data. On the global set, the SAFFRON trial, which AstraZeneca is running actually will not allow the patient crossover the EGFR - the MET TKI. So we would think in the global setting, there is a high chance they can not only demonstrate PFS, but OS benefit could potentially be also wider than we anticipated in SACHI.

And just to add on that, right? All these other trials are not MET-specific patients, right? So they are all comer. And then for the longest time that we were trying to figure out like for MARIPOSA-1 and 2, which got approved for all comers, how do they perform in MET specifics of group. So we don't know until actually the ASCO data come out at the MET-specific of group perform worse than the MET, you know ...

Onetime.

Yes. So that's a little bit interesting. I mean like we can only speculate maybe because these, like antibodies just can attach on surface of the cell, whereas for us, which is a small molecule, we can find to intracellular receptor, and that may play a role in our efficacy being superior when we do this cross-trial comparison.

Okay. Great ...

We also have seen this, right, from a clinical parties perspective. These patients have very poor prognosis. You almost have to identify the driven disease given the most effective treatment early to give them actually a second chance to see the product post-treatment therapy. So testing MET certainly is important. Well, I think the clinical physicians really realize testing the MET amplification is very important in order to support patients to live the most efficacy treatment at that point.

Maybe just one more on your last point, Michael, I think the presenter at ASCO mentioned that in the China SACHI study that the patients were identified through local FISH, mostly. But just for the global study, SAFFRON, how are patients being identified there? Is there a standard? Is it just based on local practices? How do you harmonize for that and just make sure you're identifying the correct patients?

Yes. So for SAFFRON, it's actually AstraZeneca defined the biomarker selection for the amplification, FISH and also the IHC for MET overexpression with IHC 90-plus patients. So that include even broader patient population compared with SACHI. And we think this is going to be -- I mean, it's actually quite standard. Even in the China development, we actually follow the SAVANNAH -- develop the biomarker selection criteria. So all these centrally test the biomarker in order for patients to be recruited in this trial. Yes.

Okay. Great. Maybe last one is, you talked about data potentially coming in '26. Is that still the case here? And then just sort of thinking about time lines for you and your partner to do global regulatory tilings, Will that also happen in '26 as well?

Yes. So as I mentioned, the recruitment is close to finish. And our partner projection, the SAFFRON readout will be next year. And global filing will soon follow.

Yes. Okay. Great. Maybe turning to other aspects of your pipeline. I've always felt like in the past year or 2, one of your most promising internal assets has been savolitinib, which you've worked on, and you've shown very strong data in ITP, in Chinese patients, and you've also filed on it. Can you maybe just remind us for what you saw in your China-only study? And then just sort of what rough time lines what the NMPA might be for since you filed?

Yes. Right. So we present the ESLIM-1 data at EHA last year was showing very robust durable response rate, which is the primary endpoint, right? Because just to give you a context for fostamtinib, it was the -- another Syk inhibitor, first marketed leading to the approval have overall -- I mean, the durable response rate, 18% but such, ESLIM-1 data, we show a sovleplenib in the second-line setting, ITP observed a durable response rate of 48%, which is really not only compared with the Syk inhibitor, but also different modality of treatment. This has really show very impressive or durable response rate.

So we filed for the China NDA and it was under review at NMPA. So during the report review process, we actually observed based on the discussion with the CDE, there's -- we're addressing there's impurity issue. So we actually changed the excipient for this formula and we'll continue testing the stability on the rolling base. We updated the agency about the stability data. So our current projection is going to targeting for the approval later this year.

Okay. So that would potentially be included in the next round of drug pricing considerations, if you make it through -- get a decision in this calendar year ...

June 30 tend to be the usual time. So it will be in the -- next 2026.

Okay. Got it. Okay. And then maybe just broadly speaking, I think this asset has potentially multiple applications as well as probably should be considered for global markets and other opportunities. Just in broad strokes, what sort of your global development plans here?

Yes. So we are continuing to evaluate the global development plan, right? Because as you can see, international development, you have to consider all the other competition. Now the latest observed, Sanofi filed the BTK inhibitor and also the CD38 monoclonal antibody also in the global registration. So we are actually evaluating the treatment landscape about the globin. Certainly, we'll have the thinking about how we can develop this molecule for the global market. Yes.

Okay. Great. Maybe in terms of other considerations for this molecule, you've mentioned in the past, think about follicular lymphoma, where FL as a potential adjacent opportunity here. I think, typically standard of care here in the U.S., European and most major other markets, has been BTK utilization. So can you maybe talk about the pros and cons and sovleplenib versus maybe what I think a standard of care which typically is BTKs here?

Yes. So I think what you mentioned, sovleplenib, we do have a follicular lymphoma development. We do have a pretty good data presented in this setting, right? And as you know, we also have a China right for another molecule, the EZH2 inhibitor in follicular lymphoma, tazemetostat. We actually get it just approved this year. So we are launching the product in a month or so.

So in terms of the treatment landscape, tazemetostat is our first push for the hematology product, third-line follicular lymphoma. Also in our collaboration with partnership with Ipsen, we are running a global SYMPHONY-1 trial, tried to move it into the second-line setting. That trial is ongoing combination with R2 globally. So we -- that's also our priority to move it to earlier line, second line follicular lymphoma setting.

So for sovleplenib, we are still evaluating that in terms of the treatment landscape, how we're going to develop programs. To your information also, we have another molecule is a BTK inhibitor and we are also generating quite interesting data. We're thinking about how we -- in the hematology space, how we can really fully develop our heme pipeline globally.

Great. From Dr. Su on down, you guys have excelled that working on medicinal chemistry in the small molecule space. But in recent years, you've also talked about other modalities, including ADCs and other mechanisms to some other degree. Can you maybe just at a high level, in the time we have left, talk about sort of what are your other modality efforts at least at this stage and when we might start to see a little bit of clinical data from those programs?

Yes. So earlier this year, we actually announced we are focusing on a new kind of platform. What we call is antibody target therapy conjugate, ATTC. This is the new platform we have developed in this -- really leverage our 20 years of experience in a small molecule. Linking this small molecule to the antibody. And so the first wave of antibody we selected these are clinically validated antibody.

We have a function activity in the multiple tumor type, linking with our target therapy because a lot of reports showing the toxin-based ADCs, patients readily develop resistance particularly for patients with a genetic driver mutations. So our approach will have the opportunity to addressing the resistance for the traditional ADCs because the key advantage is really by linking this antibody -- because it's traditional small molecule oral target therapy also have a narrow therapeutic window.

So if you want to have a sustained tumor suppression, they need a higher dose and then you see the safety issue. So this approach, the ATTC will allow us to deliver the target therapy precisely into the tumor and have sustained expression. The preclinical data show very robust data, have 1 dose of ATTC has 2 weeks, 3 weeks, sustain the tumor suppression.

And also, has the opportunity to combine with other treatment modality, for example, the immunotherapy, target therapy and also chemotherapy because we know a lot of company for this toxin-based ADCs is almost impossible to combine with the other standard of care like a chemotherapy in the earlier line setting.

So our ATTC approach really allow us to combine with all these different standard of care in order to move earlier line things. So the approach for us is selecting the target therapy to target with border mutation frequency and also the function mono can cover very broad tumor type and allow us to combine with different therapies to really helping to prevent the disease progression and have a higher chance to win in the earlier line setting.

So that's a focus for our company in the next few years. The first few molecule, we already nominated 3 clinical candidates, enabling the GLP tox package study now. So our first ATTC will be in the clinic this year. So we're targeting 2 IND submission this year.

Yes. Okay. Great. We're up on time here. So we'll have to end it on that note. Thanks to Michael and David for joining us here in HUTCHMED.

Thank you for having us.

Thank you.

Thank you.

Hello. Good morning and good evening. Welcome to HUTCHMED ASCO investor call. I believe some of you have already seen our ASCO data readout, among which such as that it must be the most exciting one with amazing PFS and HR. So today, we are doing this call to further help you analyze some of the data so you can better understand its implication.

As you know, before the presentation, we need to remind you of our safe harbor statement and disclaimer. The performance and results of the operations of the HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results. For better identification, please change your Zoom name to your name plus institution name. We'll keep you muted during the presentation. There will be a Q&A session for you to ask questions after the presentation.

Okay. Now let's invite our CEO and CFO, Dr. Su, to give the presentation.

Thank you, Ming, for the introduction. Hello, everyone. Welcome to the call. With me today are Michael Shi, CMO and Head of R&D, who will be available for Q&A as well. So I'll be happy to give you a very quick run-through of the key data of SACHI and also SAVANNAH as well to some extent, and we can all discuss. Next slide, please.

SACHI study was terminated following a positive interim analysis and subsequently, an NDA was submitted in China, which is currently under review. Clearly, the study met the primary endpoint of PFS with a statistically significant and clinically meaningful improvement in PFS in comparison to standard of care. Here is the clinical study design of the SACHI study. When we started the study in China in the first-line setting in EGFR mutant non-small cell lung cancer population, all first-generation, second-generation and third-generation EGFR TKIs were available. So the study was designed to allow all patients resistant to first-line EGFR TKI due to MET amplification. The patients were randomized to receive savolitinib plus osimertinib in comparison to standard double chemo platinum plus pemetrexed in a 1:1 randomization. The study was stratified based on brain metastases, TKI and also EGFR mutation types.

The primary endpoint also upon confirmed disease progression crossover was allowed. And this study was an adaptive design. And the data will be first analyzed for patients who progress on first-generation and second-generation EGFR TKI followed by the ITT patient population. The primary endpoint is the PFS. Next slide, please. The key demographic information you can see fairly well balanced of note, almost just under 40% of patients enrolled had brain metastases. Next slide, please. This is the primary endpoint. As I mentioned, the study was an adaptive design. The first analysis was patients who progressed on first, second-generation EGFR TKI. Median PFS improved from the chemo group of 5.4 months to savo plus OSI of 9.8 months, hazard ratio -- stratified hazard ratio of 0.34, obviously, highly significant. And this was followed by the ITT population analysis and the same hazard ratio and obviously highly statistically significant. In the next slide, when you look at the patients who progressed on third-generation EGFR TKI, obviously, with the approval of osimertinib and many other third-generation EGFR TKI during the study, in a real-world situation, there was a very quick switch in the first-line setting from first, second-generation EGFR TKI to third-generation EGFR TKI.

So when we look at the third-generation EGFR TKI resistant patient population, as you can see here, very consistent clinical benefit for OSI plus savo treatment. TFS improved from 3.0 months for chemo group to 6.9 months for the savo plus OSI treatment, hazard ratio of 0.32 again, highly significant, both investigator-assessed and IRC assessed results were very consistent. The looking at the predefined subgroups, as you can see the PFS benefit was very consistent for almost all predefined subgroups in favor of OSI plus treatment. Next slide, please. This is more of a benchmark -- marking comparing SACHI versus MARIPOSA-2 study in second-line setting and in patients progressed on third-generation EGFR TKI with amplification. Obviously, cross-study comparison and also the small sample sizes should take into consideration. First off, the MET detection difference. MARIPOSA 2 used NGS to detect ctDNA MET amplification.

SACHI study, FISH was used and fresh tissue biopsy was required. First off, in the MARIPOSA-2 study, only 14% ctDNA positive, while for the SAI study using the FISH, greater than 30% of MET amplification was detected. And this actually was consistent with the unpublished HUTCHMED data that not every FISH positive patient will be tested ctDNA positive. As a matter of fact, only about 30% of patients FISH positive will detect ctDNA. So a threefold difference roughly and consistent here as well between the 2 studies. Sample size, as I mentioned, relatively small. These are subgroups of the big studies, 32 versus 12 versus 30 for the MARIPOSA 2 study and in the SACHI study was 37 versus 37 patients. Obviously, clear difference in route of administration, MARIPOSA-2 all injections and SACHI study or oral administration and the MARIPOSA-2 had double chemo doublets platinum plus pemetrexed and SACHI study was chemo-free.

Looking at the clinical benefits, median PFS, 4.2 versus 3.1. So 4.2 for the Ami plus chemo versus 3.1 months for the chemo alone and hazard ratio of 0.51. There was 0.078 for the p-value, obviously probably due to the small sample sizes. But as you can see, comparing to SACHI study, median PFS, 6.9 for the savo plus OSI versus 3.0 for the chemo.

And you can see here, for these patients who progressed on third-generation EGFR TKI with MET amplification, the chemo PFS were very consistent, 3.1 for the MARIPOSA and 3.0 for the SAI study. And the clinical benefit was numerically greater for the SACHI study, OSI -- savo plus OSI 6.9 months. So comparing to -- for the chemo comparator, looking at MET amplified versus ITT in the MARIPOSA study, as you can see, 3.1 months for patients with MET amplification and 4.2 months for the ITT patient population, suggesting MET amplification is a driver and denotes poor prognosis. Evidence of CNS activity, no data was reported from MARIPOSA-2 as of yet. For SACHI study on OSI -- on savo plus OSI treatment, we have noted clear clinical benefit from both the SAVANNAH study and also the SACHI study. I'll go into this a bit further with the data.

But let's look at the next slide. So this is the -- you're looking at brain mets study -- brain mets subgroup in the SACHI study, you look at the median PFS, 6.9. And this is very consistent with the broader patient population and highly statistically significant as well. Obviously, not surprising given what we know about the brain penetration ability of both osimertinib and savolitinib, but this was published before in many publications. Let's go to the next slide.

So this is a few other key secondary endpoints -- on this slide, response rate, disease control rate and median duration of response, all significantly improved and all consistent with previously published SAVANNAH data as well. Very good response rate, close to 60% and disease control rate and the response was durable. Next slide. So on the safety, no new signal was detected and the combination [indiscernible] was well tolerated and AEs can be readily managed. Let's go to the next slide.

So in conclusion, the combination of savolitinib and osimertinib shows clinically meaningful improvement in PFS, ORR and duration of response versus chemo in the second-line setting for patients who progressed on EGFR TKI. Median PFS for the ITT patient population, 8.2 months for the savo plus RSI treatment versus 4.5 months for the chemo treatment group has a ratio of 0.34. Looking at the third-generation EGFR TKI resistant patient population, median PFS 6.9 for the savo plus OSI treatment versus 3 months for the standard chemo treatment, hazard ratio of 0.32.

And the safety profile for the savo plus OSI combination treatment was consistent with previously reported safety profile of savolitinib and osimertinib. No new safety signal was detected in the study. Okay. Next slide. So the other abstract presented by AstraZeneca, our partner at ASCO focused on CNS, again, the CNS activity of the -- savo plus OSI treatment. And actually, this was a study, a sub-study to determine the contribution of component in this patient population. Okay. Let's go to the next slide. As you can see next again. So if you look at the efficacy parameters in patients with brain metastasis first comparing savo plus OSI versus savolitinib alone, as I mentioned, this was a subcomponent of the study to determine contribution of component.

And when you look at the study as a whole, overall was 58%, again, very consistent when you compare this to the SACHI study, median duration of response, 11.8 months and the onset of response, 6 weeks, so fairly rapid. The next slide. Again, you see these patients with brain metastases, median PFS for the savo plus OSI combination 8.3 months. They're also very comparable to the SACHI study, the ITT patient population. So these patients with brain metastases benefit equally from the savo plus OSI combination treatment.

Next slide. Again, when you look at the CNS confirmed versus 43% CNS PFS also events all very consistent with the level of efficacy seen with the greater ITT patient population. Next slide. Also of interest looking at patients who develop brain metastasis on treatment. And in the plus treatment group, there were 13 patients who had PFS events or whose disease will progress. Out of the 13 patients, 0 had the CNC -- new CNS lesions or progression due to CNS lesions.

In contrast, savolitinib single-agent treatment out of the 11 patients who progressed, 6 had CNS -- new CNS lesions. So the OSI plus savo group had a very good CNS disease control. Next slide. Again, safety profile, very consistent across all studies and across all different patient population, Chinese versus -- or Asian versus non-Asians, all very consistent, and it can be easily managed. Next slide. So again, savo plus OSI provided meaningful clinical benefit to patients who progressed on EGFR TKI with MET amplification and demonstrated CNS activity or CNS disease control using this combination. Next slide. So I think this wraps up the data summary, and we'll take questions from the audience, if any.

Okay. Thank you very much for the great presentation. Now we are open for the Q&A session. [Operator Instructions] Due to time, please limit your number of questions to 1 or 2 and only questions about our ASCO data. Now the first question comes from Alec Stranahan from Bank of America.

Guys, can you hear me?

Yes. Okay. Great.

Okay. Great. Yes. Thanks for running through the data at ASCO and congrats on the progress from SACHI and SAVANNAH. I guess on the SACHI combo of savo plus osimertinib, I appreciate the OS profile is still evolving. But do you think you'll need static benefit on OS for approval? Or is PFS enough given sort of this is how the study was designed? And curious if you see OS as maybe feeding into physician decision to describe over other options if approved?

Okay. Thank you, Alex. Obviously, for the SACHI study, as I mentioned, crossover treatment was allowed for the study design. So OS statistic significant OS improvement is not allowed -- I'm sorry, is not required for the approval. And it's not even a primary endpoint. So we don't expect that OS -- significant OS is required. And we did see a trend of improvement in OS. I think it will be further published.

Okay. Next question comes from Jonah Chen at China Merchant Securities International.

I have a question on the, especially on the patient selection. So I remember you have a slide showing the comparator versus the MARIPOSA and J&J and you show the ctDNA landed from the -- left from the [indiscernible] patients that we included in the trial, not from the general non-small cell lung cancer patients. Is that right?

Sorry, I didn't get your question. Can you repeat your question?

Yes. I mean the MET amplification detection, you still hear it is a data set from the samples that we recruited for the trial, right? It's not the amplification detection rate for the real-world population. Is that right?

The amplification right here, like 30% for SACHI, 14% for MARIPOSA-2. These are study patient population and the savo patients who progress on the third-generation EGFR TKI treatment. So it's not in novo, it's not for like -- it's not for the first-line patients. These are patients who progress on the third-generation EGFR TKI treatment.

So the second question is that in the upcoming second line third-gen TKI, we've seen lots of new modalities targeting various targets like PD-1 VEGF or [indiscernible] or any other candidates. So Frankly, I think the MET amplification is the most direct [indiscernible] assay problem that we need to target. So how do you compare our SACHI over the [indiscernible] combination versus the current available other dual target or some other ADC target?

So again, we believe MET amplification is an oncogenic driver and patients not poor prognosis. The only way to compare the data is you have to compare with the biomarker detection of MET amplification, for instance. All other studies, they have not published data on the MET amplified patients as we pointed out, right, the IT or the all-comer data is not very useful for comparison.

MARIPOSA-2, they just revealed their subgroup data on patients with MET amplification, so we can do the comparison. I would expect based on the hypothesis that MET amplification is an oncogenic driver and these patients will do worse than all comers or all the ITT patient population. So all other studies chemo plus, VEGFR or VEGF plus PD-1, they need to reveal -- they need to publish the MET amplified subgroups for better comparison. So I can't tell you how the SA data compared to all other possible treatments in second-line setting. But overall, I think for patients, I think that what's important in the clinics for patients who progress on the third-generation EGFR TKI, they need to get their tumor samples tested. And if they are MET amplified, I think OSI plus savolitinib offers a very good treatment for them.

One last question on the CNS subset of the Phase II SAVANNAH. I think it's quite encouraging for us to read the PFS data, the separation for our -- the SAVANNAH combination. And what is the current available statement for all the post-TKI treatment, but they have the CNS metastatic patients? Is there any available kind of care for these subject?

I think always, right, patients with brain metastases, the prognosis is much worse than CNS is absent. So that's why we are highlighting the CNS activity of savo plus OSI treatment. I think it's really important, the disease control in the CNS patients. I think this -- a lot of patients ultimately die because of the brain metastases. So again, I think clinically clinicians will pay attention to the patient's brain or CNS status. It's -- unfortunately, chemotherapy -- standard chemo, they don't -- currently, the standard chemotherapy does not offer very good coverage in the CNS. You can imagine all the chemo plus PD-1 plus VEGF or anti-VEGF. I think ultimately, we need to accumulate more data to do pooled analysis looking at CNS control. But we are very happy that savo plus OSI for these patients, at least they benefit very well from the treatment.

Next question from Adam McCarter at Cavendish.

Congratulations on the data as well. And the one question for me is more of a commercial sort of market opportunity one. So you previously disclosed that the EGFR non-small lung cancer MET aberration market in China is worth around $850 million to $1.2 billion. I'm assuming that estimate likely included both MET amplification and MET overexpression. So could you provide any guidance or assumptions around the market opportunity specifically for MET amplification in China, which is the target population for SACHI's potential approval?

Well, Adam, I think at this point, what we do know is in the first -- in the second-line setting, we were just talking about SACHI study, the MET amplification following third-generation EGFR TKI treatment is about 34% in the SAVANNAH study and about 35% from the SACHI study. You are right that overexpression can also be targeted. As a matter of fact, the SAVANNAH study target both MET amplification and MET overexpression together based on the criteria set forth for SAVANNAH study, it was about 40%. So that information is what we know today. So you can kind of estimate the patient population size following the first-line treatment. In the first-line setting, which we have a study ongoing called SANOVO study targeting MET overexpression, which is depending on the cutoff, MET overexpression in EGFR mutant non-small cell lung cancer is rather high based on the reports available, it ranges from 40% to 80% in that range, again, depending on the cutoff. So the majority of patients who are EGFR mutation positive will have MET overexpression as well. Whether that's a targetable patient population using savolitinib osimertinib combination remains to be seen. The study is still ongoing.

So from that, I think you can estimate the patient population size. I think in terms of commercial sales, where it's going to peak or -- it's a lot more complicated because depending on the -- again, depending on the various markets, the pricing, the duration of treatment, all these remains to be seen from the SANOVA study in first-line setting. But second line, we have more information, as I said, right, roughly about 40% of patients Duration of response is about somewhere between 8 and 9 months. So I think you can probably do your model using the information available from the SACHI study and SAVANNAH study and -- but again, pricing can vary widely from markets to markets.

Excellent. And if I could just follow up with one more question. With the SACHI data now accepted under priority review in China and a potential approval over the next 12 months, could you share how you're preparing for a potential launch? And I'm thinking particularly around biomarker testing infrastructure for amplification and an overall positioning with the EGFR TKI treatment landscape.

Yes. I think we are working very closely with our partner in China, AstraZeneca China team. So there will be a companion diagnostic kit to go with the final approval. And MET amplification diagnostic kit is relatively mature. It's widely used in hospitals already. I think Astra team will -- they're obviously responsible for commercialization, and they will be providing the kit to train the pathologists in the hospitals. But it's been widely used already in the hospitals in China. So yes, I think we will be working closely with Astra team in China as soon as it's approved.

Thank you, Adam. Due to the limited time, we'll take the last question. it's from Khalil Fenina at Goldman Sachs. No. I think she's not offline. Okay. your line is open.

Hi, everyone can hear me?

Yes.

This is Khalil in for Paul from Goldman Sachs. Just a really quick one from us. Just on the MET amplification testing. We really appreciate the slide on the comparison between MARIPOSA-2 and SACHI. Could you just talk about like the implications that has for studies going forward, whether it's SAFFRON or others in terms of the participation criteria? Are you or is there any planning to require testing via FISH instead of ctDNA? And then what about, and what implication does it have for like the commercial landscape in terms of testing patients once the drug is on the market?

Thank you. Yes, that's a very good question. the SACHI study, fresh biopsy was required and the tissue FISH was a standard test. SAFFRON study, again, fresh biopsy required, but both FISH and IHC for overexpression were used. So the study -- the SAFFRON study is still ongoing. Ultimately, there will be 2 companion diagnostic kits for the SEPFRON study, Standard FISH, same as SACHI, but also IHC for MET overexpression as well. So -- as I talked about, NGS for ctDNA MET amplification that is convenient, but it under detects by almost 70%. It can only detect about 30% based on our published data. Patients with FISH MET amplification, only 30% of those will test NGS positive. So for patients who are -- who progress on EGFR TKI at this point of time, I think FISH test on biopsy is most reliable.

Got it. So is that going to be the requirement going forward? Sorry, I just missed what you said on the 2 companion diagnostics. Is that specifically just for SAFFRON or in general?

That's for SAFFRON. And for SACHI, MET FISH is the only CDx. And the patient population size, it basically FISH alone is about 30% -- somewhere between 30% and 35% when you add overexpression in IHC, it increases to about 40%. So greater majority of patients overlap basically 90% of patients overlap.

Okay. Thank you, everyone, and thank you, Dr. Su. Sorry for the, we have to end the call to time of limited time. So you may end the call, and have a nice day.

Buh-bye. Thank you.

m,anak you. Thank you.