Okay, I think, let's get started. Hello, good morning and good evening. Welcome to HUTCHMED 2025 ASCO Investor Call. I believe some of you have already seen our ASCO data readout, among which, SHI study must be the most exciting one, with amazing PFS and HR. Today we are doing this call to further help you analyze some of the data so you can better understand its implication. As you wrote before the presentation, we need to remind you of our safe harbor statement and disclaimer. The performance and the 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 CSO, Dr. Su, to give the presentation. Thank you, Ming, for the introduction. Hello everyone, welcome to the call. With me today, Michael Shi, CMO and head of R&D, will be available for Q&A as well. I'll be happy to do a very quick run-through of the key data of SHI and also Savannah as well to some extent, and we can all discuss. Next slide, please. SHI 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 statistically significant and clinically meaningful improvement in PFS in comparison to standard care. Here's the clinical study design of the SHI 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. The study was designed to allow all patients resistant to first-line EGFR TKI due to MET amplification. Patients were randomized to receive savolitinib plus osimertinib in comparison to standard of care double chemo platinum plus pemetrexed in a one-to-one randomization. The study was stratified based on brain metastases, TKI, and also EGFR mutation types. The primary endpoint, upon confirmed disease progression, crossover was allowed. 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 + osi of 9.8 months. Hazard ratio, stratified, hazard ratio 0.34, obviously highly significant. This was followed by the ITT population, design, analysis, and the same hazard ratio and obviously highly statistically significant. Okay, 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. When we look at the third-generation EGFR TKI-resistant patient population, as you can see here, very consistent clinical benefit for osi + savo treatment. PFS improved from 3.0 months for the chemo group to 6.9 months for the savo + osi treatment. Hazard ratio of 0.32, again, highly significant. Both investigator-assessed and IRC-assessed results were very consistent. Looking at the predefined subgroups, as you can see, the PFS benefit was very consistent for almost all predefined subgroups in favor of osi + savo treatment. Next slide, please. This is more of a benchmarking, comparing SHI versus MARIPOSA- 2 study in second line setting, and in patients progress on third generation EGFR TKI with MET amplification. Obviously, cross study comparison is, 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. SHI study, FISH was used, and fresh tissue biopsy was required. First off, in the MARIPOSA- 2 study, only 14% ctDNA positive, while for the SHI study using the FISH, greater than 30% of MET amplification was detected. 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 two studies. Sample sizes, as I mentioned, are relatively small. These are subgroups of the big studies, 32 versus 30, 12 versus 30 for the MARIPOSA- 2 study, and in the SHI study was 37 versus 37 patients. Obviously, clear difference in route of administration, MARIPOSA- 2 oral injections, and SHI study oral administration. The MARIPOSA- 2 had double chemo, double chemo doublets, platinum plus pemetrexed, and SHI 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. It was 0.078 for the p-value, obviously probably due to the small sample sizes. As you can see, comparing to SHI study, median PFS 6.9 for the savo + osi versus 3.0 for the chemo. As 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 SHI study. The clinical benefit was numerically greater for the SHI study, osi, savo + osi, 6.9 months. Comparing to the, for the chemo comparator, looking at MET amplified versus ITT for the, in the MARIPOSA study, as you can see, 3.1 month for patients with MET amplification and 4.2 month 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 SHI study, on osi, on savo + osi treatment, we have no clear clinical benefit, from both the Savannah study and also the SHI study. I'll go into this a bit further with the data. Let's look at the next slide. This is the, you're looking at a brain met study, brain met subgroup in the SHI 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. 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, very good response rate, close to 60%, and disease control rate, and the response was durable. Next slide. On the safety, no new signal was detected and the combination was well tolerated and AEs can be readily managed. Let's go to the next slide. 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 progress on EGFR TKI. Median PFS for the ITT patient population, 8.2 months for the savo + osi treatment versus 4.5 months for the chemo treatment group, has a hazard ratio of 0.34. Looking at the third-generation EGFR TKI resistant patient population, median PFS is 6.9 months for the savo + osi treatment versus three months for the standard chemo treatment, with a hazard ratio of 0.32. The safety profile for the savo + osi combination treatment was consistent with the previously reported safety profile of savo and osi. No new safety signal was detected in the study. Okay, next slide. The other abstract presented by AstraZeneca, our partner at ASCO, focused on CNS, again, the CNS activity of the savo + osi treatment. Actually, this was 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. If you look at the efficacy parameters in patients with brain metastasis versus, you know, comparing savo + osi versus savolitinib alone, as I mentioned, this was a subcomponent of the study to determine contribution of component. When you look at the study as a whole, the ORR was 58%. Again, very consistent when you compare this to the SHI study, median duration of response 11.8 months and the onset of response, six weeks. So fairly rapid. The next slide. Again, you see these patients with brain, brain metastases, median PFS for the savo + osi combination, 8.3 months. It also is very comparable to the SHI study, the ITT patient population. These patients, patients with brain metastases benefited equally from the savo + osi combination treatment. Next slide. Again, when you look at the CNS confirmed versus, you know, 43%, CNS PFS events, all very consistent with the level of efficacy seen with the greater or ITT patient population. Okay, next slide. Also of interest, looking at patients who develop brain metastasis on treatment. That's, in the savo + osi treatment group, there were 13 patients who had PFS events or whose disease will progress. Out of the 13 patients, zero had new CNS lesions or progression due to CNS lesions. In contrast, savolitinib, savolitinib single agent treatment, out of the 11 patients who progressed, six had CNS, new CNS lesions. The osi + 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. Savo + os 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. I think this wraps up the data summary and we'll take questions from the audience if any. Okay, Dr. Su, thank you very much for the great presentation. Now we are open for the Q&A session. If you have a question, please use the raise hand function or you can also put your question in the chat box. Due to limited time, please limit your number of questions to one or two and only questions about our ASCO data. Now the first question comes from Alec Stranahan from Bank of America. Alec, your line is open. Hey guys, can you hear me? Yes. Okay, great. Yeah, thanks, thanks for running through the data at ASCO and congrats on the progress from SHI in Savannah. I guess on the SHI combo, of savo + osimertinib, appreciate the OS profile is still evolving, but do you think you'll need static benefit on OS, you know, for approval or is PFS enough given sort of this is how the study was designed and, you know, curious if you see OS as maybe feeding into physician decision to describe over other options, if approved. Thank you. Okay, thank you, Alec. Obviously, for the SHI study, as I mentioned, crossover was, crossover treatment was allowed, per the study design. So OS, statistically significant OS improvement is not, is not required, for the approval. It was, it's not even a primary endpoint. We don't expect that the OS, significant OS is required, and, we did see a trend of improvement in OS. I think it will be further published. Okay, great. Thank you. Okay, now, next question comes from Jonah Chen at China Merchants Securities International. Jonah, your line is open. Hi, thanks for the update. I have a question on the subfill and the static, especially on the patient selection. I remember you have a slide showing the comparison study versus the MARIPOSA by NJ and J and you show the ctDNA lancet from the coverage patient that we included in the chart, not from the general non-small cell lung cancer patient. Is that right? Sorry, I didn't get your question. Can you repeat your question? Yeah, I mean, the MET amplification detection, you still hear it, it is a dataset 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 rate here, like 30% for SHI, 14% for MARIPOSA- 2, these are study patient populations, and these are for patients who progress. Yeah. On the third-generation EGFR TKI treatment. It's not de novo, it's not, it's not for, like, you know, it's not for the first-line patients. These are patients who progress on the third-generation EGFR TKI treatment. Thank you very much. The second question is that, in the upcoming second line, post third-gen TKI, with lots of new modalities targeting various targets like PD-1 and VEGF or CHOP2 or any other candidates. Frankly, I think the MET amplification is the most direct signaling pathway problem that we need to target. How do you compare our study or the savolitinib combination versus the currently available other dual targets or some other ADC targets? Thank you. Again, we believe MET amplification is an oncogenic driver, and patients denote 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 ITT or the all-comer data is not very useful for comparisons. 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 the ITT patient population. All other studies, you know, chemo plus or VEGFR or VEGF plus PD1, you know, they need to reveal, they need to publish what the MET amplified subgroups, for better comparison. I can't tell you how the SHI data compared to all other possible treatments in second line setting. Overall, I think for patients, 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 + savolitinib offers a very good treatment for them. Thank you very much. One last question on the CNS subset of the phase two Savannah. I think it's quite encouraging for us to read the PFS data, the separation for the Savannah combination. What is the current available treatment for all the post-TKI treatments? They have the CNS metastatic patient. Is there any available standard of care for this subset? I think, you know, always, right? Patients with brain metastases, their prognosis is much worse than if CNS is absent. That's why we are highlighting the CNS activity of savo + osi treatment. I think it's really important, the disease control in the CNS patients. I think a lot of people, a lot of patients ultimately die because of the brain metastases. Again, I think clinically, clinicians will pay attention to the patient's brain or CNS status. It's, unfortunately, you know, chemotherapy, standard chemo, they don't, you know, the standard currently, the standard chemotherapy does not offer very good coverage in the CNS. Yeah. I, you can imagine all the chemo plus, you know, plus PD-1 + VEGF or anti-VEGF. I think ultimately we need to accumulate more data to, you know, do pooled analysis looking at CNS control. I think, but I'm, you know, we are very happy that savo + osi for these patients, at least they benefit, very well from the treatment. Thank you very much. Thank you. Yeah, quite well. Thank you. Okay. Next question from Adam McCarter at Cavendish. Adam, your line is open. Hi, hi, hi there. Thanks for taking my question and congratulations on the data as well. The one question for me is more of a, of a commercial sort of market opportunity one. You previously disclosed that the EGFR and non-small cell lung cancer MET aberration market in China has worth around $850 million- $1.2 billion. I'm assuming that estimate likely included both MET amplification and MET overexpression. Could you provide any guidance or assumptions around the market opportunity specifically for MET amplification in China, which is the target population for SHI's potential approval? Thank you. Adam, I think at this point, what we do know is in the second line setting, we were just talking about the SHI study, the MET amplification following third-generation EGFR TKI treatment is about 30, 34% in the Savannah study and about 35% from the SHI study. You are right that overexpression can also be targeted. As a matter of fact, the Savannah study targeted both MET amplification and MET overexpression together, based on the criteria that set forth for the Savannah study was about 40%. That information is what we know today. You can kind of estimate the patient population, patient population size, following the first-line treatment. In the first line setting, which we have a study ongoing, what called a SNOVO study targeting MET overexpression, which is, you know, depending on the cutoff, MET overexpression in EGFR mutant non-small cell lung cancer is rather high based on the reports available, ranges from 40% to 80% in that range, again, depending on the cutoff. 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. From that, I think you can estimate a patient population size. I think in terms of commercial sales, where it's gonna peak or it has, it's a lot more complicated because depending on the, you know, again, depending on the various markets, the pricing, the duration of treatment, all these remains to be seen for the, from the SHI, from the SNOVO study in first line setting. Second line, we have more information, as I said, right? Roughly about 40% of patients, duration of response is about somewhere between eight and nine months. I think you can probably do your model, you know, using the information available from the SHI study and Savannah study. Pricing can vary widely from markets to markets. Excellent. Thank you very much. If I could just follow up with one more question. With the SHI 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? I'm thinking particularly around biomarker testing infrastructure for MET amplification and then overall positioning with the EGFR TKI treatment landscape. Thank you very much. Yeah, I think we are working very closely with our partner in China, AstraZeneca China team. There will be a companion diagnostic kit to go with the final approval. The MET amplification diagnostic kit is relatively mature. It's widely used in hospitals already. I think the 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 being widely used already in the hospitals in China. Yes, I think we'll be working closely with the Astra team in China as soon as it's approved. Excellent. Thank you very much and congratulations again on the results. Thank you, Adam. Due to the limited time, we took the last question. It's from [Cleo, Vanina], at Goldman Sachs. Cleo, I think, oh, I think it's offline. Oh, okay. Cleo, your line is open. Hi everyone. Can you hear me? Yeah. Oh, great. Hi. Thank you for taking our question. This is Cleo calling in for Paul from Goldman Sachs. Just a really quick one from us. Just on the MET amplification testing, you know, we really appreciate the slide on the comparison between MARIPOSA- 2 and SHI. Could you just talk about the implications that has for, you know, studies going forward, whether it's SAFFRON or others in terms of the participation criteria? Are you, you know, are you or AstraZeneca planning to require testing via FISH, instead of ctDNA? And then what about, and what implications does it have for like the commercial landscape in terms of testing patients once this drug is on the market? Thank you so much. Thank you. Yeah, that's a very good question. For the SHI 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, you know, were used. The Saffron study is still ongoing. Ultimately, there will be two companion diagnostic kits for the Saffron study, standard of FISH, same as SHI, but also an IHC for MET overexpression as well. As I talked about, NGS for ctDNA MET amplification, that is convenient, but it under detects by almost 70%. Or, you know, it can only detect about 30% based on all unpublished data. Patients with FISH MET amplification, only 30% of those will test NGS positive. For patients who progress on EGFR TKI, at this point of time, I think FISH test on biopsy is most reliable. Got it. Is that gonna be the requirement going forward? Sorry, I just missed what you said on the two companion diagnostics. Was that specifically just for SAFFRON or in general? That is for SAFFRON and for SHI, MET FISH is the only CDX. Got it. Got it. All right. Thank you so much. The patient population size, it basically FISH alone is about, somewhere between 30% and 35%. When you add overexpression IHC, it increases to about 40%. So greater majority of patients, they will, you know, will overlap, basically 90% of patients overlap. Okay. Yeah, that makes sense. Thank you. Okay. Good. Okay. Thank you everyone, and thank you Dr. Su. Sorry for the, we have to end the call because of the limited time. You may end the call and have a nice day. Bye-bye. Thank you. Thank you. Thank you.