Hello, everyone. Good evening and good morning. Thank you for joining the 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. As usual, we will have a Q&A session at the end where you can press the raise hand button to ask questions, or you can type the question in the chat box. Please make sure you have your name and your company name on the screen. Now let me welcome our CMO and Head of R&D, Dr. Michael Shi, to start today's presentation. Michael. Thank you, Ming. Good morning, good evening, everyone. Happy Halloween. Today, I'm going to give you a research update for HUTCHMED pipeline. Today we're going to talk about our main antibody target therapy conjugate platform and really showcase some of the new next generation platform. Also, recently, last week, we actually presented our first candidate, A251, at the URTC meeting in Boston. I'm going to highlight some of the progress and show you the results and our overall preliminary development plan strategy. I'm going to show the late stage pipeline progress with a closing remark. We're going to start a Q&A session. For the ATTC platform we introduced to the investor early this year, it is really the new development for the past three years at HUTCHMED. We really are looking at some of these progress and the platform. Before we go to that, we really talk about the current development in the toxin-based antibody-drug conjugate, ADCs. As we know, there are 19 ADCs that have been approved worldwide. Despite the design and the rationale expanding the therapeutic index, the traditional toxin-based ADCs also have a very similar toxin profile. Macrotubule and the topoisomerase inhibitor, those have some common features for toxin-based toxicity such as myelosuppression, thrombocytopenia, and hepatotoxicity, and some of the ocular toxicity or neurotoxicity. There is really the limitation. There is certainly room to improve to overcome these challenges. The HUTCHMED antibody target therapy conjugate is really designed to target a protein required for the cancer growth. One of the important features, what we believe, it has the synergistic combination activity with antibody because the antibody we chose really has the antibody and the function, really has a potential synergistic effect. More importantly, we know the ADCs have a very difficult profile to combine with the traditional chemotherapy, which is often required for frontline chemotherapies. We think the ATTC will overcome this chemo resistance and also have the potential to be dosed long term. From toxicity perspective, although it has the antibody-based toxicity, we believe the antibody target therapy payload has the low on target off target tumor toxicity. 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. We think this will be a unique platform to really enhance some of these and overcome some of the resistance and difficulty for the toxin-based ADCs. When we select these, development for ATTC, really selecting some of the functional antibody and conjugated with the target therapy, which traditionally are small molecule, have poor solubility and very hard to link to the antibody. We really working on the linker and the payload to have this ATTC platform developed. With the lower free target therapy in the circulation and also have a wider therapeutic window compared with the oral systemic exposure. It has a great opportunity because they can combine with the other therapy, for example, target therapy, immunotherapy, and more importantly, the chemotherapy. These will potentially have an opportunity to be used in the frontline. 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 PAN PI3K, mTOR pathway. The PAN pathway, PI3K, AKT, mTOR pathway is a very attractive therapeutic target because it has a very coverable, very broad range of the tumor type, have a high frequency mutation in some of the most common tumor types, 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, it's very high mutation rate. Also in other common tumor type, it also have a very high frequency. 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. Talking about the mutation, is really play a role in the toxin-based ADC resistance. This is one of the reports last year from ESMO showing the HER2 ADC, the sediment. Bidalten RC48, in breast cancer patient type. In the clinical study in the overall patient population, the PFS and the ORR is better, but with patient with PAN altered pathway, really show for poor prognosis, activity. For example, the PFS is lower, response is lower because of these driver mutation really leading to the drug resistance for ADC product. Also in the DESTINY CRC01, showing the driver mutation for PIK3CA and also RAS mutation. Patients with these mutations also have a lower response rate and a shorter PFS compared with the wild type patient. There is opportunity to really improve, to develop 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 the pipeline of development, including multiple companies invested in this PI3K inhibitor development, but with very few success. The first generation and second generation pretty much halted due to the systemic toxicity. Later on, there are mTOR inhibitors, for example, everolimus, PIK3CA alpha and capiversitin with AKT inhibitor, leading to the approval, but they also have a pretty hard to handle, tolerated profile. Also, the significant overall survival has been hampered. Two weeks ago, we see the new PI3K inhibitor, genotolerance, really showcased 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. Targeting PAM pathway alteration really showing as a promising approach for breast cancer. For example, in the slides 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 these mutations. In the HER2 positive patient population, including hormonal positive or negative patient population, the PI3K PAM pathway mutation is representing close to 40%. In the HER2 negative patient population, triple negative patient population, these mutations even have a higher presence. Really presenting a big opportunity for developing PI3K inhibitor targeting breast cancer patient population. In the genotolerance study, we do see there is an improved PFS and activity in not only the overall patient population, representing inhibiting target in HER2 positive patient population also show good activity. Adverse events such as stomatitis also pretty high. Here is the profile for our PAM PI3K pathway inhibitor, PI3K/PIKK inhibitor. This is HMPL-606. In short, we represent as 606. This is our first targeted PI3K inhibitor using as a payload. The profile for this molecule, as shown in the KINO, as you can see, the major inhibition really shows focus on the PI3K and PIKK activity with very high selectivity and very small off-target activity. This is the profile compared with the other kind of PI3K or PIKK inhibitor, gene tolerance and ductolerance and bilparite. 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. 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 used in the breast cancer cell lines. You can see very robust dose-dependent inhibition of the PAM pathway, including AKT, S6 or so. Also, in the PIKK pathway, when you enhance the PIKK pathway by treating with sublimizing, you can really activate all these DNA repair processes. Using the payload 609, you can see also a dose-dependent inhibition of this pathway. In the panel of 130 cell lines, we can see, in many cell lines with the mutation of a PAM pathway, HER2 pathway alteration, RAS pathway mutation on the other cell lines, 609 has a very potent activity with the IC50, about one nanomolar. On the right-hand side is the cell growth inhibition of 609 by tumor type, and also shows, demonstrates a nanomolar range and also high potent activity across many different tumor cell lines. Now let me talk about the antibody part. The first proof of concept molecule we developed is using HER2 as an antibody. We all know HER2 alteration really leads to a poor prognosis in cancer in many tumor types. For example, HER2 amplification or overexpression has been shown as a poor prognosis factor. HER2 amplification or overexpression leads to the patient with a shorter half-life, short of a lifespan. Also, HER2 overexpression and amplification really cover many tumor types. What we are also looking at, the anti-HER2 therapy, is really, for example, developed by trastuzumab, is a functional antibody with the intact FC and leading to ADCC activity. It works by blocking the extracellular domain cleavage to prevent the formation of its active form of HER2 and also blocks the dimerization of the molecule and reduces the signal transduction pathway. Also mentioned the antibody, leading to the antibody-dependent cell-mediated cytotoxicity. Also, the HER2 antibody downregulation through the endocytosis, through the lysosome. To sum up for our concept and for the development of ATTC, we use the HER2 as a therapeutic antibody and the PI3K/PIKK pathway inhibitor as the payload. This provides opportunity to really inhibit the most major oncogenic driver and the downstream signaling pathway of HER2. It has the potential to overcome the resistance for trastuzumab-based therapy. Also, the antibody and the payload will have a synergistic activity with the enhanced anti-tumor activity. This PAM PI3K-based HER2/ADC, ATTC is really expected to increase the efficacy and the synergism and also improve the safety profile to overcome some of the narrow therapeutic window for the traditional PI3K inhibitor. Now let me move to the first candidate, A251. We showcased this molecule at the ERDC meeting last week in Boston. Here's the structure for the PI3K, the A251. The payload is 609 and is a highly potent PI3K/PIKK kinase inhibitor and has the potential synergy with the HER2 antibody. We also show you some of the data. We'll have the potential for combination with chemotherapy as an ATTC and also show the bystander effect. The antibody portion is the HER2 trastuzumab biosimilar and with the cleavable linker and with the drug to antibody ratio as a four. Here's the in vitro binding activity. It does show A251 and the HER2 antibody has a very similar binding activity. Also, this figure shows the internalization of the antibody, A251 ATTC, and also the naked antibody. At 37 degrees, we can see the internalization. On the right-hand side, you can see the intracellular trafficking of the antibody drug conjugate. The blue color is showing the nuclear staining and the red color is relatable with the HER2 antibody. Green color is showing the lysosome. 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. Also, we show you the activity for payload 609. Now for the whole antibody target therapy conjugate, it has a similar feature as the payload alone. When you do the in vitro cell inhibition, I say, in HER2 positive PI3K mutant cell lines, we can see a potent inhibition, dose-dependent inhibition of the phosphorylated AKT, S6, for example, really showing the target pathway inhibition and leading to cleaved CASPASE, PARP inhibition and leading to apoptosis. Also, on the right-hand side is the PI3K/PIKK pathway inhibition, showing this molecule also has an in vitro inhibition of the PIKK pathway and also leading to DNA damage. When you use the A251, it has increased the DNA damage. 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 tested, HER2 positive cell line, with PI 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. In the HER2 alone, pan-altered pathway, it still demonstrates potent activity, although the potency compared with the HER2 overexpressed positive patient population, it has less potency and also has some less magnitude effect in HER2 negative cell lines. Here down the right-hand side, we show the bystander effect in the HER2 positive cells. We can see for A251 showing very potent bystander tumor killing effect. It doesn't work on the HER2 negative cell lines, but if you co-culture the HER2 positive and HER2 negative cell lines, you can clearly see the robust tumor killing with the bystander effect. Also, we test this molecule in the HER2 resistant cell line. On the left-hand side, we can see the comparison of the A251 with in HER2. In cells, in breast cancer cells, using the siRNA silencing of the SLX4, which is one of the key genes to turn on the resistance, because it's one of the DNA repair enzymes. When you really silence the SLX4, you can see a right shift of the potency of the payload DXD or DS8201 in HER2. It needs a higher concentration and also has less inhibitory effect compared with the A251. In comparison with the payload itself and the A251, you can see there's no right shift and the payload and the ATTC remain the same potency to inhibit this resistant cell line. On the right-hand side is the developed cell line resistant to either HER2 or the payload. You can see, again, that the DXD-treated cells and the inherited-treated cell have a right shift and a less potent killing effect compared with the parent cell. In the Payload 609 and the ATTC A251, you don't observe this right shift and maintain the same tumor killing effect, cell killing effect. Here's one of the proof of concept studies we have done for A251. 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, IP injection, biweekly. The pink color is the trastuzumab plus 609. You have also increased cell growth inhibition. A251 at the 10 and the 30 milligram per kg really shows robust tumor inhibition activity and causes tumor regression. This is very important because this is a HER2 positive and PTEN loss xenograft model. We can see a single dose injection of A251 can have a two-week sustained tumor suppression. Unlike the small molecule cell, you need multiple dosing to have a modest anti-tumor effect because this is actually the MTD level of the payload for 609. Also, on the safety side, on the left-hand side is the same model. You can see the ATTC A251 does not lead to 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 a quite significant body weight loss and the recovery. When you dose again, it will lead to additional body weight loss. This is really the maximum tolerated dose for this small molecule payload. As you can see, in the preclinical model, the activity of the A251 has a more favorable safety profile compared with the small molecule or small molecule combined with the antibody. On the right-hand side is a very classic example because the small molecule 609, when you see the dose in the animal, it has a very transient and high glucose increase, same with the 609 plus antibody. On the other hand, A251, the glucose level remained unchanged because the PI3K inhibition leading to hyperglycemia is really a classic hallmark for this class of PI3K inhibitor. In this preclinical setting model, we really demonstrate, using the ATTC combat concept, you can really increase the safety profile for this PI3K inhibitor because it's a targeted delivery of these conjugate into the tumor cells, leading to the release and inhibited 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. Here is the two model we have shown: 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 positive PI3K mutated model. The red line is the 10 milligram per kilogram in HER2 as a control. I can see in these two models, we can see a faster and deeper response for A251, leading to the tumor growth inhibition compared with the DS, compared with the inherited cell. Here we also test the panel of HER2 low, pan-altered cell line in the mitral cancer cell line, and in the tumor xenograft model. Again, we can see in the HER2 low model, we can see a more rapid tumor growth inhibition of A251 compared with in HER2 in the upper model. In the cervical cancer model, we can see the activity of A251 is similar to in HER2. We further test some of the model with DALT pan pathway alteration. In HER2 positive pan non-altered xenograft model, we can see in HER2 and A251 has about similar anti-tumor activity. In all of the model we have tested, we can see the A251 pretty much have a stronger activity or at least comparable to DS8201 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, you know, sustained exposure. The 609, the free payload, which has remained very low concentration compared with the conjugated ATTC. On the right-hand side we also conducted 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 monitored the time course for the phosphor AKT, phosphor S6. You can see there's a time-dependent inhibition of this pan pathway. H2AX, gamma H2AX is a marker for DNA breakage. You can see the increased DNA damage and also leading to increased cleave the caspase with the representing the apoptosis. The CD68 is a marker for macrophage inspection. You can see the macrophage infiltration into the tumor cell. You can see really leading to the ADCP, antibody-dependent cytotoxicity. Also, we look at the distribution of the payload in the tumor cell. In the tumor cell, you can see a sustained and high exposure of the payload into the tumor cells, and the systemic and the plasma level actually remained low. This is just representation of the inhibition of the pathway leading to the pan pathway and the cleave, with leading, inhibition, leading to apoptosis and DNA damage and ADCP activity. In summary, A251 is the first-in-class PI3K/PIKK inhibitor conjugated with a HER2 antibody. It has robust and potent anti-tumor activity in the HER2 positive model, without or without the pan moderation. Also, represent showing quite good activity in HER2 low tumor model with the pan mutation. It has a fair PK profile and has a very improved safety profile compared with small molecule payload itself. We have completed the GLP-12 study and filed a China and U.S. IND. We already received the FDA clearance for this U.S. IND and our phase one clinical studies is expecting 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 one, we're going to start with the single dose escalation. We are now enrolling HER2 positive or low patient population. The pan pathway alteration will be tested retrospectively. It's not the requirement for enrolling patients. Further dose expansion will be tested in HER2 positive, pan positive, HER2 positive, and pan negative, non-altered pathway patients. We will also test the HER2 low and pan mutated patient population. We will further expand in multiple tumor type with or without pan alteration. We will test, when we define the dose for a single agent, we also will start the A251 in combination with stem cell chemotherapy in the earlier line in the frontline setting. We are going to test the solid tumor in the HER2 low patient population with the pan alteration. Here is the, as you can see from these, molecule with the, we have pretty mature HER2 pathway. Functional antibody and also the very broad PI3K inhibition. The pan pathway is quite common compared with other driver mutation, ALK, ALK alteration, EGFR in Western patient, and HER2 amplified mutated patients. Pan pathway alteration really representing a very broad range of tumor type. If the new incidence for all these cancer types is very high. Also in the breast cancer, we can see HER2 positive patient population represented 15 to 20% patient by the standard testing. As we know, HER2 low patient population also have a very robust percentage, representing 40 to 50%. The HER2 negative patient population is a smaller percentage. This will really provide a good opportunity and targeting a larger HER2 expressed patient and also with the PI3K mutation because HER2 is also one of the downstream, because PI3K is also downstream of the HER2 activation pathway. We think this molecule really can cover very broad range, tumor inhibition in the breast cancer area. Just thinking about the HER2 negative second line breast cancer with the genotolacy, for example, recently demonstrated activity, the market size representing about $5 billion. We believe even HER2 negative, part of the significant portion of the patient will have HER2 expression. These will can still potentially be patients benefit from the A251 in addition to HER2 positive patient population. This molecule really representing a good, good opportunity for the broader tumor type development in the future. I show you the first molecule, A251, as our leading molecule, which will enter clinic later this year. Also, here you can see the pan pathway alteration really covered very broad range of tumor type, lung cancer, breast cancer, colorectal cancer, breast cancer, for example. The HER2 pathway expression also show pretty covered broader range of the tumor type. Here represent our opportunity for our first molecule. By the same concept, we think other important antigen, right, SHRP2, EGFR, 4P7H3, 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 a inhibiting major pathway driver mutation cell lines, we think this ATTC platform can really cover very broad range of tumor type, representing huge opportunity for the development. Our first molecules already get a U.S. IND clearance and starting enroll, we'll start to enroll patients soon. The second molecule, A580, which is with a different antibody and we have not yet disclosed, but we are targeting to have the phase one initiation early next year in China and the U.S. Third molecule, A530, and will also enter the clinic in the second half of 2026. We kind of update you about the ATTC platform and the lead molecule enter the clinical development. I'm going to cover some of the new development in the late stage pipeline. HUTCHMED has really developed a deep pipeline, covering multiple tumor types. Our first approved product, FRUZAQLA, we already approved in the colorectal cancer and worldwide, ex-China has been covered by Takeda. In China, we also continue to develop additional indication. FRESCO-1 was reported early in the middle endometrial cancer. We get a NMPA approval for pMMR endometrial cancer, December 2024. Also, second line RCC. We have showcased this FRESCO-2 trial data at the ESMO two weeks ago in Berlin. I'm going to show you some of the highlight of the data. The NDA has been submitted and under review in NMPA. Our expectation is we're going to approve late next year. Also, MET inhibitor, ORPATHYS, also making tremendous progress. We showed the clinical data of SAVOLITINIB SAMETA study in second line EGFR mutated, the MET amplified patient population. In combination with osimertinib, demonstrate the robust clinical improvement. It was approved NMPA, under fast track review in June 2025. Our global partner AstraZeneca has also presented data in SAVANNAH, really demonstrated the high and clinical mean effect in durable response. 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 overexpressed lung cancer, has the potent, has the data readout next year. SANOVO is the first line MET overexpressed patient population in combination with osimertinib. We have fully enrolled the patients in August. We are anticipating the GC gastric cancer in MET amplified patient. We are conducting single line registration trial and with the patient enrolled in April and the readout with the potential NDA in this year. SAMETA is in the probably renal cell carcinoma. It's also led by our global partner AstraZeneca. Also, the other approved the product through FADINEB in China. We are also having a phase two three study in first line pancreatic cancer, in combination with PD-1 and the chemotherapy. Phase two is fully enrolled and the data readout we're going to showcase later this year. TASMETOSTAT is the global first-in-class molecule, EZH2 inhibitor. We licensed from IPSN. We have completed our bridging study and the drug was approved earlier, March 2025, by NMPA in the third line follicular lymphoma. We are making great progress in the second line lymphoma trial. Also, for SOVOBOPLANIB, this is our SYK inhibitor, through the ESLIM-1 study, in the second line immune thrombocytopenia, we have a SAMETA and NDA. As we know, there is an impurity issue we have addressed. We reached agreement with the CDE, really defined the intake level and moving forward with the resubmission early next year. Also, our second line autoimmune disease is warm autoimmune hemolytic anemia study. We already completed the enrollment, with the potential readout and NDA next year. Newer pipeline is the second line FGFR2 inhibitor, fenugreatinib and also with the potential for NDA this later this year. Our dual ADH1 and two inhibitor, renocitinib, also in the phase three study in the AML. Here's the FUCONIDET with the Centella MAB combination versus standard of care in China, asinib or everolimus. The data, FUSICA2, has been presented at the ESMO Congress through the oral presentation by Professor Zheng Hualu. Here's the trial design: FUCONIDET plus Centella MAB versus the investigator choice of asinib or everolimus. The clinical endpoint, primary endpoint, is the BERC review PFS, by independent radiology assessment. It was demonstrated in the primary endpoint by BERC analysis, PFS. FUCONIDET plus Centella MAB versus comparator really showed very robust activity, with a median PFS of 22 months versus 6.9 months of the asinib everolimus group. It's highly, with a hazard ratio of 0.37. It's a very similar report, results, for the investigator assessment. Also, in terms of response rate, by BERC review and the investigator review, we can see over doubling of the overall response rate by Centella MAB and the FUCONIDET combo, really showing this activity in this patient group with a very high MME. 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. It's highly significant, very robust response rate. It's highly clinical, meaningful. The NDA is currently under review by CDE, where it's expecting approval next year. Also, we are conducting the phase two three, first line pancreatic cancer trial. SOVOBOPLANIB and the Carlizumab, which is Hungrace PD-1, along with the standard of care gemcitabine plus nab-paclitaxel versus gem versus nab-paclitaxel. The phase two results have been accepted by the ESMO Asia. We'll present this, the top line data, in the ESMO Asia meeting in December. On the ORPATHYS side, the MET Savannah study by AstraZeneca presented data at ELCC in March in Paris, showing the high response rate of 56% and the 55% of the BERC review. In MET exon 14 skipping patient population, we also presented our confirmatory phase three study at the ELCC and really showing a very impressive overall survival, for the second line 25 months and first line 28 months. ELCC clearly demonstrates this is one of the longest overall survival has been reported among all the MET inhibitor in MET exon 14 non-small cell lung cancer setting. SATG data really provide a future growth. The ASI plus ORPATHYS really showing the clinical robust activity was presented as an 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 in, with the infinity, versus SUTENT. These trial has been recruited. The readout will be next year. Also, AstraZeneca lead, SAFRON study also has reached the enrollment target. We expect the results next year. If positive, this will really be hopeful for our second molecule can go to the global NDA. In China for the SANOVO study, first line ASI plus ORPATHYS in MET amplified overexpressed patient, enrollment completed. We are really hoping for the readout later. On the gastric cancer in MET amplified patients, we also will have the potential to submit the NDA. The next molecule is the EZH2 inhibitor, TASMETOSTAT. We have conducted a bridging study really showing a very consistent study compared with the global, global trial, IPSN trial, and really showing a robust, complete response rate, about 18%. 63% overall response rate and a very high percentage of the clinical benefit rate. The drug has been approved. We are further conducting, along with our partner IPSN, the global Symphony One trial. This is the TASMETOSTAT in combination with OSQUARE, rituximab, and lenalidomide versus the placebo with OSQUARE. We are very happy that the China wild type patient has completed enrollment. This global trial, if positive, will not only move the TASMETOSTAT to the second line, but also has the potential not only in the mutant patient population, but also the wild type patient. Our partner IPSN and HUTCHMED are really working towards the full recruitment for this patient group. Fenugreatinib is the FGFR2 inhibitor. We have previously agreed with the CDE to use the single line registration in order to potentially have the conditional approval in the registration cohort for the two week on, one week off schedule. 87 patients were recruited. We are expecting the data readout and, if positive, will follow the NDA this year. SOVOBOPLANIB is the SYK inhibitor. We first reported our ESLIM-1 result at the EHA, really showing a very robust or durable response rate of 48%. Last year we showed the follow-up long term study, which demonstrated the overall response of 81% and durable response for 51%. It has very fast onset to increase the platelet. Unlike the TPORA, which also stimulates the platelet production but also has the opportunity to overshoot, TPORA has a potential for thrombosite, thrombosite embolytic events, which in the ESLIM-1 study for SOVOBOPLANIB, the thrombocytopenia, thromboembolic event is not a safety concern. It has a highly differentiated clinical activity and safety profile. We reported a lot earlier this year, right? Although the previous NDA was delayed through an impurity issue, we have reached the agreement with CDE, really defined the intake level. We continue to conduct a stability study and bioequivalent study with this new formulation. Our targeted resubmission is in the first half of next year. We have completed the enrollment of our phase three ESLIM-2 trial in Waiha, autoimmune hemolytic anemia. We're potentially with the readout next year and, if possible, the submission in China. Here's the phase one data we have shown in the AIHA patient population. In previously treated AIHA patients, we have demonstrated the overall 66% overall response rate and also the 47% durable response rate. It really shows the highly robust activity for this SYK inhibitor, not only in ITP, but also in AIHA patients. I gave you overall the ATTC platform and also the late-stage pipeline advancement. To summarize, for today and beyond, we are really striving for global commercial success. Our partner Takeda really showed the FRUZAQLA 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, if the SAMETA data is positive, will be our second molecule that can essentially be registered internationally. ELUNATE is FRUZAQLA, and it is continuing to grow with the new indications. The new mutual cancer approval will certainly help the commercial development and launch. Also, with the new RCC trial, we hope the FRUZAQLA plus sintilimab in the RCC trial could receive approval in the next 12 months. SAMETA, of course, SAMETA and SULANDA led by the AstraZeneca development, will all have phase three readout next year. If positive, they will potentially be strong catalysts for the company. SOVOBOPLANIB, PDAC in combination with PD-1 and chemotherapy, will have the data readout. Again, the FGFR inhibitor, fenugreatinib, and also the savolitinib in gastric cancer with the MET-amplified patient, will all have the potential for NDA submission. More importantly, looking to the future, we're thinking our next-generation technology platform, antibody target therapy conjugate ATTC platform, has huge potential. We have multiple selective candidates currently that will enter the clinic. The first is already reached the IND clearance in the U.S. The company has a strong balance sheet and also, you know, relatively small market cap. We think our future potential really has a great opportunity. Along with our robust cash position, certainly we continue to look at in-house, in-licensing, and out-licensing opportunities. Hopefully, our effort and advancement can be appreciated in the investment road and really lead to long-term growth and generate value for our shareholders. With that, I'll just wrap up and open for questions. Okay, thank you, Dr. Shi, for the detailed analysis. Now we open the Q&A session. Due to limited time, please try to limit the number of your questions to one or two. You can use the raise hand button. The first question comes from Alec Stranahan from Bank of America. Alec, go ahead. Hey guys, thanks for taking our questions and 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 optimizing safety to align it with frontline combo opportunities, especially when we're talking about assets like A251 that go after broadly expressed targets. Thank you, Alec. Yeah. It's a very good question. For us, right, of course the traditional development is really try to see some activity in the late stage setting. That's why we enroll patients with previously treated patients. Our belief is, you know, in the target patient population, for example, HER2 positive, and with a PEN, altered or non-altered patient, we will expect to see the activity. Certainly, you know, we explore multiple cohorts in the late stage setting. If we have a defined patient population, could have a more robust activity, could certainly lead to the potential accelerated registration approval. The main difference here for the ATTC, for A251 example, is what we consider is the opportunity to really advance to the frontline. We have demonstrated multiple models have a synergistic activity with the traditional chemotherapy or standard of care therapy. A lot of these toxin-based ADCs really have difficulty to combine with other chemotherapy. That's why we think this is an advantage for us. Also, this is a unique opportunity to really take on this, combine the U.S. China trial, right, to really simultaneous development to advance our pipeline. Because, as you know, the FDA is really encouraging the earlier line development, right, instead of just the frontline setting, late line setting, because, through this Project Front Runner activity. We think, even at the, you know, when we have the dose escalation and even, we have this Bayesian 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. Our hope, we have shown these combinations not only with the chemotherapy and some even the model with the toxin-based ADC also shows synergistic activity. 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 care versus standard care. We think that will be the future growth driver. 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 very strong limitation. We believe that's where we can compete, in broader tumor type, because this unique profile for this ATTC platform. Okay. That makes sense. Thanks, thanks Michael. I guess one on the frontline PDAC opportunity for SOVOBOPLANIB, I guess what do you sort of see as the bar for efficacy in the phase two readout in December, in combination? I guess how should we be thinking about it, the activity of SOVOBOPLANIB here versus PD-1 alone? Given the control arm only includes gemcitabine, not paclitaxel. Pablo Paxel, thank you. Yeah, we have looked at quite some historical data, right? You know, because pancreatic cancer is highly fibrotic and is usually considered as an immune desert. PD-1 plus chemo alone really hasn't shown very robust activity. From our perspective, the surfetinib is not only a VEGF inhibitor, it's also an inhibitor of CSF1R and FGFR. It really has very strong potential through our early study. The initiation is Professor Dy's IAT trial with the PD-1 and surfetinib combo with different chemo regimens, showing the OR rate is about over 50%. Compared with standard care, about 25%. In particular, the OR reported at ASCO GI earlier this year showed the OS benefit is really beyond 12 months, about 15 months. That's what we think, not only for the PFS side, but OS side, this combination has a unique advantage compared with chemo alone or chemo plus PD-1 alone. The bar, we think, is if you compare with the Gem Pak Lee Taxol, usually the overall survival is very short, like nine months or so. I think with over a year OS, with the robust PFS, we think this combination really shows a pretty impressive opportunity from the early phase data. The data presented will really show how we evaluate the bar. You will see this soon. That will really define what is the bar we want to overcome to lead to the phase three. Okay. Thanks. Congrats on the progress. Thank you, Alec. Next question from Goldman Sachs, Khalil Felina. Khalil, go ahead. Hi everyone. This is Khalil calling in for Paul Choi. Thank you so much for taking our questions. 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 like the second largest commercial opportunity here in the longer term. Just given the emergence of nuclear medicine in the space, we're just curious, in your view, do you envision perhaps running a study in pluvicto-experienced patients to see if those types of agents amplify PAM at all? The second question was just on ITP. You mentioned looking to further develop it ex-China. Just curious what the status was on that. Thank you so much. Thank you, Khalil. You know, for the prostate cancer, right? 'Cause what we think, the payload targeting PI3K/PIKK has very broad opportunity, really, against multiple tumor types. We think, at least from a development perspective, we have many options where to go to. Certainly we'll probably choose a few tumor types through the company, see what is the lead line setting, we'll read out what will be. Also, start a combo study to really get the clinical evidence-driven kind of a development plan, right? Certainly, in the evolving nuclear medicine, I see the Pluvicto data is quite impressive. In terms of future development, we probably will have to see how the expansion cohort reads out and where the strongest evidence or opportunity will lead us to guide our future development plan. Certainly, prostate cancer is down the book, but we have to look at how the data read out in many tumor types to really make the decision for the early line development in the future. In terms of SOVOBOPLANIB, we have quite good communication with the CDE because it was submitted and under review. If we reported early this year, we certainly have reached the mutually agreed AI limit to be acceptable. In order to accomplish that, we have to make a change in the new formulation. Through this, we are going to work on the BE study and also with that, stability testing, to really satisfy the requirements. The targeted resubmission is early next year. We think with this clear agreement guidance, we have a path for SOVOBOPLANIB in China, not only for the ITP, but also with WIHA when it's read out, earlier next year. In terms of global development, we believe this newly agreed limit with the CDE is the most industry standard, including the global FDA and EMA, is a breedable intake limit. That formulation will certainly satisfy the global development for this product for a global potential. That really opened our door. We mentioned we paused the U.S. and EU development just because of this issue. I think we are in a position to really look at international development, as you can see in the ITP study at least, for example. The Eastland One data clearly show highly durable response rate, and the long-term exposure demonstrates the sustained platelet increase and durable response compared with all these existing products, including a new one, right? The FCRN with the rosabutinib and all this activity, we think SYK inhibitor really represents a probably best-in-class modality in this patient group. Because Eastland One data is really heavily pretreated patient, they failed all the first line and also the T, 75% of patients failed the TBORA. Certainly in the heavily pretreated patient, we can see this most robust ORR really showing this as an opportunity. Certainly we will reposition and really think what is the fast track for the global development. In parallel, I think we can re-engage some of the discussion with the partner and should really leverage this molecule's unique, because this dual mechanism, inhibiting the engulfing of the platelet or red blood cell, and also blocking the B cell activity. These are certainly strong clinical evidence, activity. We think this, with this newly developed formula, certainly has a pretty good opportunity to be further developed globally and open the door for discussion for future partner. Yeah. I know. That's a good point. Also, by the way, Khalil, we're going to present our long-term, the final Eastland One data at ASH. It has been selected as an oral presentation. I think it will reignite the interest for SOVOBOPLANIB. That's very helpful. Thank you so much. We look forward to that oral presentation. Thank you very much, Dr. Shi, and congrats on all the progress again. Thank you. Great. Thank you, Khalil. Next question comes from Jefferies, Clara Dong. Clara, go ahead. Hi. Thank you. Thank you for taking my question and appreciate for putting together this very informative presentation. Two from us. 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 this integration will support your long-term strategic vision, and how do you prioritize your indication selection for those programs? Also, given the novelty of the ATTC platform, would you be able to share any color in terms of what's a bar for safety you are looking for for the very first ATTC candidate? Thank you. Thank you, Clara. For ATTC, I think, just really leverage our traditional HUTCHMED small molecule expertise. For target therapy, we really work on the linker and the payload to really have an opportunity to generate this molecule and platform. Because from antibody selection to the target therapy payload selection really provides some good opportunity. I think the first wave of development, of course, we are really science-driven, target-driven, and thinking where the development will really lead 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. With the further development and with the antibody, with the target, payload, the selection, I think we have many, many opportunities, many different types, just really cover a very broad range of tumor types. The development probably will focus initially in the area we think we have a strong interest to be further developed. Of course, it's data-driven, science-driven. If it's proven to be successful, right? You asked about the bar of the safety or so, at least from the preclinical data, we really see this platform can overcome some of the traditional limitations for small molecule for this systemic exposure because, as the example I show you for A251, in the GLP tox study, we don't see this hallmark for the PI3K small molecule inhibitor. For example, hyperglycemia, myelosuppression or so. Just from preclinical data, we know because this is a selected target delivery of the ATTC into the tumor cell and the very low exposure of the small molecule payload in the circulation really demonstrates the safety margin, compared with the systemic exposure for small molecule. We think the safety level really, from the preclinical data, really shows us this has a substantial increase from the traditional small molecule approach. The combination with all the multiple target development, multiple antibody development, we think it really generates a unique platform. 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, you know, ATTC and probably more dual payload kind of the ATTC also in the research stage. I think this will represent huge opportunity for our platform. Of course, you know, there are only limited resource. We have to focus on area where we, expertise to really develop fast proof of concept. Certainly with the future, potential partnership, we certainly think they can really broaden the indication, broaden the development, because these all these molecule have a potential targeting, broader tumor type, high frequency driver mutation, overcome the resistance. The opportunity is really, quite huge from our perspective. We'll be the focus of our, company's new effort for these, globally competitive first-in-class assets. Appreciate the call. Thank you. Great. Thank you, Clara. Our next question from Kevin Dish, then Adam McCarter. Adam, go ahead. Thank you. Thanks for the presentation. Really interesting. I guess the first question I have, the safety data for A251 looks really encouraging, as you said, Dr. Shi, particularly the absence of the elevated blood glucose levels. You mentioned that this may relate to the compound's targeting ability, which is helping to limit systemic toxicity. Could you elaborate on whether you're seeing differential inhibition across AKT isoforms in tumor cells? Some of the tolerability issues seen with earlier pan-AKT and PI3K inhibitors have been linked to the AKT2 inhibition. It'd be useful to understand how A251 compares mechanistically in that regard. Thank you. Thank you, Adam. Also, very good question. Of course, we are actually looking at these, you know, all these potential PI3K, AKT pathway inhibition, right? In short, right, 'cause we do see, you know, 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 a thousandfold or even higher kind of a differentiation. Pretty much all these free payload concentrations we have seen are well below the IC50 level to reach the target inhibition. That's why we do see the safety profile margin. Also, through monitoring, we understand, you know, because the dose we select for the tox study, we really monitor the threshold. We can see, you know, certain, I would say, on-target kind of an AE profile, but it is reversible, it is dose-dependent. That's why we feel this ATTC provided a very safe window for our future development. Hopefully, certainly, we hope this will be represented in the human study, right? 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 a multiple huge opportunity for the next wave of product we are developing. That's great. Thank you. If I could just ask a second question. 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? Thank you. Yeah. I think the field is really evolving very rapidly, right? I think all the scientists are really thinking about different ways, right? You can see there are different approaches, right? Even you see this, the most recent example, right, Inovan, there's the linking of immunotherapy with the target therapy, I mean, the antibody, right? 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 really has longstanding small molecule expertise. I thought our strength is really in the linker and the payload. Also, we have really been working in multiple target therapy development areas. I think with a deep understanding of the biology, coupled with strong medicinal chemists and new, newly more innovative novel antibody or bispecific antibody, we think we are in a very strong position to really lead and innovate in this field. Yeah. Thanks, Dr. Shi. Thanks again for a great presentation. Thank you. All right. Thank you, Adam. 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. We wish you a wonderful day. Bye-bye. Thank you.