HUTCHMED (China) Limited (HCM) Earnings Call Transcript & Summary

Hello, everyone. Good evening, good afternoon and good morning. Welcome to HUTCHMED R&D Day. Today, we are very happy to have our CEO and CSO, Dr. Su Wei-Guo on the line as well as Dr. Mike Shi, our Head of R&D as well as our CMO, in here with us. Today, we are going to share with some exciting prospect of some of our key products with you. And right now, everyone on the line is in a muted mode. But at the end of the presentation, when you have questions, you can raise your hand or type your question in the chat box. Now without further delay, let me hand over the time to Dr. Su. Dr. Su?

Thank you, David. Good morning. Good evening. Welcome again to HUTCHMED R&D Day. We hope to periodically share with you the progress of our programs. And today's session is designed to give you an update on our late-stage programs. And Mike Shi will do most of the talking. Before we get there though, I just want to give you a quick overview on our late-stage programs. fruquintinib, as you know, our flagship product. It's now approved in China, obviously, for third line and above, colorectal cancer. It's been on the market in China for almost 6 years now with over USD 100 million in sales last year. And late last year, fruquintinib was approved in the U.S., for late stage colorectal cancer and launched immediately after the approval in November last year. And recently, in June, EMA approved fruquintinib in European countries. So we are working together with our partner, Takeda, to prepare for the launch in European countries. And the NDA is still under review in Japan and many other countries around the world. Savolitinib, our selective MET inhibitor. It's approved now in China for MET Exon 14 skipping non-small cell lung cancer. And we've just submitted an NDA in China based on the confirmatory study again in MET Exon 14 skipping non-small cell lung cancer, including treatment-naive patients. And it is also in several other studies in lung cancer as well as gastric cancer intended for registration in China. Most exciting, we expect NDA filing in the U.S. based on the SAVANNAH registration or pivotal study later this year. It will be our second product for registration outside China. Surufatinib, we'll provide you an update on clinical development in first-line pancreatic ductal adenocarcinoma. Recently, we shared some data -- we published some data at ASCO and also ASCO GI. And based on the encouraging study surufatinib will now enter into a Phase II/III study for this very difficult-to-treat disease. Obviously, surufatinib is on China market for a few years now for neuroendocrine tumors. And it is now pretty much the prescription lead in this -- for this particular disease with over 20% market share. Very exciting sovleplenib. You're going to hear more about from Mike. NDA is under review with priority review status granted. We expect, hopefully, approval before end of the year for immune thrombocytopenia, which is actually an autoimmune disease, our first product for the immune disease. Sovleplenib is also in a registration Phase III study for a related disease called wAIHA or warm version of autoimmune hemolytic anemia and you're going to hear a little more about it as well. Also exciting, we just kicked off our international clinical development of sovleplenib for autoimmune disease, specifically ITP and wAIHA as the initial indications. And in China, obviously, as we anticipate the approval later on this year, we are preparing for the launch of this product. HMPL-306 our IDH1/2 dual inhibitor enter into Phase III registration studies in China for recurrent and refractory AML. And obviously, as you know, it's a very exciting product with high potency and selectivity as well as excellent brain penetration. So it could be suitable for glioma, for instance. So more to come, obviously, for this compound, particularly in solid tumors. Now not on this slide, but also now in the registration stage are our in-license EZH2 inhibitor, tazemetostat. NDA was accepted in China with, again, priority review granted. The first indication is a late-stage follicular lymphoma. And this product, together with our partner, Ipsen, is also in a global Phase III, including China, in second-line follicular lymphoma. And also, obviously, it is also approved in the U.S. for epithelioid sarcoma and with potential for other solid tumors. We are quite excited about the potential in solid tumor area. Another product, HMPL-453, our selective the EGFR -- FGFR inhibitor is also now in pivotal Phase II in cholangiocarcinoma with FGFR 2 mutations and rearrangement. So we also look to complete enrollment and hopefully file for approvals maybe next year. So all in all, we have 7 late-stage products and this. And for almost every one of these products, we are looking to develop for new indications to maximize the clinical as well as commercial value of these products. And these products together will drive HUTCHMED growth for years to come, certainly for the next 3 to 5 years and beyond. So today, Mike will give you an update on surufatinib, sovleplenib as well as HMPL-306. And we also look to give you an update on our early programs in due course. So with that, I now invite Mike, to give you an update for the 3 products I just mentioned. Mike, please.

Yes. Thank you, Dr. Su. It's a great pleasure to here -- to be here to update our key programs, yes. So as Dr. Su said, right, so we are going to highlight some of the key program for our first wave product, surufatinib. We are expanding this into the clinical development for pancreatic cancer. And this is in the big market, and it is the incidence in China about 100,000 cases and with the estimated market size of $800 million to $1 billion. And as the main clinical therapy at this moment is really the chemotherapy as a strain. And globally also has an incidence of 500,000 cases and representing a high unmet medical need and there is. So this is one of the area I'm going to update you about the indication expansion, development for our first wave products for surufatinib. And also very exciting is the second-wave product, sovleplenib, is a highly specific Syk inhibitor we developed in-house. The initial indication is targeting the immune thrombocytopenia. In China, there are about 250,000 actively treated cases with a market potential of [ $500 million and $700 million ]. And globally also has the incidence of some 57,000 cases with a prevalence of 500,000 cases. And with the current marketed product globally is around 50 -- $5 billion range. And the new product front, third-wave compound, the first dual inhibitor, IDH1/2, dual inhibitor. Our initial clinical development also have an updated presentation for the AML at EHA. And with the incidence above 20,000 cases and the China market, of $100 million to $200 million. And also, there is other potential in other disease indications. And also globally, there are about 190,000 cases in AML. So first, I'm going to update you about sovleplenib. We presented key data last month at the European Hematology Association meeting. And this is potentially the best-in-class Syk inhibitor and also the first-in-class compound in China. And also, we developed in-house, it is our first innovative product. We already submitted NDA accepted by NMPA with the priority review with the hope to get the approval later this year. And so there are several fronts. We're going to update you about the sovleplenib. The NDA already under priority review and also we kick out the registration portion of the clinical development for a Phase III portion of the trial for wAIHA in China in May this year. And also the oversea developments already started in U.S., EU and Australia. And also, we have preclinical data and the evidence there are more autoimmune disease indication we can pursue. First, I'm going to give you an update about the ITP and immune thrombocytopenia is with very limited treatment options and with the first line pretty much the glucocorticoid treatment and second line with the TPO/TPO-RA agent. And fostamatinib, which is first inhibitor approved by FDA and -- but have a limited durable response with a durable response rate is only 18%. And overall, the patients have a high unmet medical need, have a poor quality of life and due to the fatigue, activity restriction and anxiety and that impacted life and the work. So on the right-hand side is the recent report by IQVIA about the assessment of the China market for autoimmune thrombocytopenia. And there are 41,000 newly diagnosed cases and also 215,000 patients under active treatment, equally important as about half of the patient 215,000 patients actually lost; follow-up primary reason due to noneffective treatment or the costs associated with -- for treatment. So this is a highly untapped market. And globally, there are 50,000 cases and 520,000 prevalence. And also there's multibillion dollar products currently on the market. First, I'll give you a very short update about the autoimmune thrombocytopenia, the ITP is autoimmune disease. The body generate immune antibody attack is on platelet in the blood. And as a result, it is lower the platelet and increase the bleeding. And so most of the patients, when they first diagnose it, their initial symptoms, right, like a bruising and bleeding and also bleeding in a nose or the mucosa. And also there could be a long-term effect there, right, for the patients who have the internal bleeding and also some of the critical cases have intracranial blending can lead to actually in capacity and also even death for the patient. So there is a huge unmet need for the patient with ITP. So the initial diagnosis, the patient with clinical criteria less than 30,000 platelet level as they could be asymptomatic or with minor bleeding. And the standard treatment is high-dose glucocorticoid treatment less than 6 weeks, but most of the patients over 50% -- 50% to 70% of the patients do have -- do not have a long-lasting response relapse and they could persistent or refractory ITP. And subsequent treatment, which is the second and third-line treatment primarily based on the patient preference and also the development like I mentioned before, the TPO/TPO-RA is the widely used second-line treatment like eltrombopag, romiplostim. And also the anti-CD20 antibody rituximab patients, somewhat patient treated with splenectomy. And even though there are some newer version of TPO/TPO-RA treatment and fostamatinib as a first Syk inhibitor approved with ITP. There are still -- after second-line treatment, there's very limited option because the traditional way is recycling for all these agents, but not have very doable response rate. So sovleplenib, we think with ESLIM-01, our Phase III trial conducted in China based on the clinical endpoint, right, the primary [indiscernible]. And China, and they already accepted by the NMPA in January. So just a few words of our mechanism of action for spleen tyrosine kinase or Syk. This is a key singing pathway. It primarily work in the Fc receptor [ CLR ] or B-cell receptor and interacting all these immune cells and leading to all the downstream effect autoimmune disease, inflammatory disease or even hematologic malignancy. And clinically, there is strong evidence, clinical proof of study and also fostamatinib was the first approved Syk inhibitor. There are also potential other autoimmune indications, for example, rheumatoid arthritis, systemic lupus erythematosus, SLE or could also be malignant [ non-Hodgkin's lymphoma ]. And the major treatment, right, I mentioned about glucocorticosteroid and Rituximab and [ splenectomy ] really targeting the, blocking the cells, Treg and the B-cell to produce auto antibody. And the other class of drug TPO-RA is really stimulating the bone marrow megakaryocyte to produce more platelet. So these -- the primary mechanism for these existing therapy, what is different for the sovleplenib, the Syk inhibitor inhibition has a dual mechanism, not only they can block their autoimmune B cells to produce auto antibody, it also work on the macrophage, blocking the macrophage to re-engulf and degrade the antibody [indiscernible] platelets. So they had the dual mechanism really have a potential to really treating the root cause for autoimmune disease. So one difference for sovleplenib compared with the first generation of Syk inhibitor fostamatinib, it has a highly specific target on Syk, not only had higher potency compared with the R406, which is the active metabolite for fostamatinib. It's also a highly specific inhibitor only the Syk pathway. For fostamatinib not only hit the Syk pathway, but also inhibit about 20 other kinases. So undoubtedly causing the off-target toxicity. So a lot of undesired effect, for example, the GI toxicity, this inhibiting effect on the VEGFR inhibitor leading to hypertension, really have a narrow therapeutic window for fostamatinib. So for the next-generation sovleplenib actually, we have a higher potency on the target of Syk inhibition, but also have less off-target effect with reduce our targeted toxicity. In the preclinical model, in the anti-mouse CD41 treated mice, they just limiting the human autoimmune ITP. And you can see on the left-hand side, there is a very rapid depletion of platelet level and treated with sovleplenib and can sustain the platelet at a higher level. And the gray bar is the IVIg, which is another commonly used ITP therapy. So preclinical, there's a good evidence inhibiting Syk pathway while maintaining the platelet level. So last month, we presented our pivotal trial, ESLIM-01 study and EHA study as oral presentation. So I'm going to briefly update you about the key top line results for ESLIM-01 in the EHA. So this is a Phase III randomized multicenter double-blind placebo-controlled trial conducted in 34 centers in China. And the patient population is on ITP with patients with a diagnosis over 12 months and also received 1 prior line therapy and patients could allow to have a concomitant ITP therapy, 1 ITP therapy when they enter the study if they're under stable condition. It's a 2:1 randomization trial so planned 300-milligram QD doses worth placebo in the pretreated patient population. And there's a 24-week double-blind treatment period for patients who did not respond after 12 weeks treatment will allow to enter the open-stage study. And the primary endpoint is the durable response rate, which is defined by the platelet count over 50,000 at 4 of the 6 visits in the 14 to 24 weeks and not counting at the rescue therapy. And secondary endpoints are overall response rate, time to respond and the reduction of rescue therapy and concomitant ITP at baseline and the WHO bleeding score and Quality of life. And there are 3 stratification factors baseline platelet counts less than 15,000 or higher than 15,000, concomitant anti-ITP therapy, yes or no, prior splenectomy, yes or no. So these basic demographic for this ESLIM-01 trial. And the highlight the 3 red box here is the 3 stratification factors. You can see this as very balanced between the treatment on the placebo arm with the baseline ITP comp, less than 15,000, 60% to 60%. As splenectomy and also the concomitant ITP treatment about 33% or 32%. So it's highly balanced and which the other parameter and as you can see, that is underlying here, is the baseline ECOG score for 21% vs 13%, which is slightly imbalanced. And also, the prior ITP treatment in the treated arm is 75% patients who previously treated TPO or TPO-RA versus 65% of the placebo arm and also the bleeding score, which is also higher, 69% versus 53%. So in general, as you can see, in counting non-stratified patient population. Overall, the treated arm has actually more severe patients with ITP. Here is the primary endpoint, the ITT sets. Sovleplenib significantly improved the durable response rate compared with the placebo. What I really want to print out here, you can see because this is heavily pretreated patient there are 4 lines of average 4 lines of treatment for either placebo or sovleplenib. And the placebo has really -- there's just no durable response, 0% versus sovleplenib group, we have 48.4%. This is really exciting because so far, counting the durable response rate, this is the highest for all the products were approved in this experimental condition. So far, we observed the highest durable response rate and highly significant with P zero p-value 0.0001. And also some key clinical parameters, at least one plate counts over 50,000, which is the overall response rate is 71% versus 16%. And also patients with 2 consecutive platelet counts over [ 30,000 ] and also increased double from the baseline level in the 0 to 24 weeks also is very high in the treatment arm is 73% versus 6% in the placebo. And also the other clinical key endpoint is platelet count over 30,000 and increased with 20,000 baseline and 75% versus 22%. So all these high robust clinical criteria for platelet increase has been demonstrated in the sovleplenib treatment. And also looking at the subgroup analysis and highly consistent among all the different subgroups, regardless gender, baseline platelet and TPO/TPO-RA treatment, concomitant medicine treatment, all these, right? And also the anti-CD20 antibody treatment is highly consistent. There is a wider boundary for the prior splenectomy. It's also favorable for the sovleplenib group, although the interval is wider. This is probably because it's a small number of patients, only like 8 patients in this splenectomy, which is also reflecting the clinical treatment paradigm projects in China. Also, we can see the platelet increase is very rapid. So the top purple line is the patient with a durable response. And the middle line is the total patient with sovleplenib treatment and the lower line is a placebo arm. As you can see, after 7 days, the 1 week, so the platelet already increased over 50% -- 50,000 and sustained at a high level. And so the onset is very rapid. The overall duration of response in the responder is 18 weeks in sovleplenib versus 2.6 weeks in the placebo group. Another area is very interesting as we're looking -- we look the sovleplenib treatment is highly consistent in the prior ITP therapy. As you can -- this is a heavily pretreated patient average line, prior therapy is 4 line therapy. So in patients with a prior therapy, less or equal to 3 lines and 4 line or higher than 5 line, all the durable response rate, over response rate and the proportion of patients with a consecutive platelet count over 30,000 and double from the baseline are all consistently favor sovleplenib group. And even though in the placebo group in the less treated, heavily pretreated patients, you see some overall response. But as the patient on the right-hand side, you can see when they reach the 5 line or 5 line, literally 0 response and the sovleplenib group which is still a large portion of the patients have a variable robust and highly consistent durable response rate or overall response rate. So it's really from all these clinical parameters, demonstrate that clinical response data and highly reproducible regardless prior line of therapy. And other endpoint, we also see sovleplenib reduced rescue therapy in patient if there's a condition by judgment of investigator, they can use rescue therapy, either IVIg or platelet infusion, these are significantly reduced in the sovleplenib treatment group compared with the placebo group, only 22% of patients during the treatment received the rescue therapy, which is over 10% or less patients has a rescue therapy compared with placebo arm. And also another very important parameter, as you recall, about 33% of patients. When they enter the trial, they have concomitant ITP therapy, most of them are corticosteroid. And for the sovleplenib-treated patient, there is significantly a higher portion of patients, 27% versus 10% have patients with reduced dose reduction or even discontinuation of the baseline concomitant medicine treatment because if the platelet reach over 100,000 and over 4 weeks by the criteria, by judgment for the investigator there, they could potentially reduce or discontinue the concomitant medical treatment but keep the sovleplenib. And also the WHO bleeding score also significantly decreased in the sovleplenib treatment arm. In terms of Quality of life has been measured by SF-36. All the 8 domains looks favorable to the sovleplenib treatment. What I highlight here is the key function, physical functioning, energy and fatigue level and general health, these are very important quality of life measurement for ITP patients. The sovleplenib treatment has reached the statistically significant improvement in these domains. So general, the patient quality of life is improved in the ESLIM-01 trial. Also, I want to show you here because traditionally, if you look at the ITP field when fostamatinib was launched, there were generally in the medical community, they think the Syk inhibition may now be as potent or effective because fostamatinib for there is 2 Phase III trial definitely reached durable response rate above 18%. But from our analysis, really, it's not the Syk pathway. It's not critical or important for the ITP but actually it's the drug itself for sovleplenib because not only as you recall about fostamatinib is a pro drug, it needs to be converted to a metabolized into the active component, R406. But also from the -- because of the off-target effect -- side effect have a higher toxicity and limited dose level, it could be reached. So from our analysis, you need to have a sustained target inhibition for Syk inhibition with the EC50 above C trough of 47-nanogram to inhibit this exposure. So fostamatinib is only less than 12% reached the target inhibition level. But sovleplenib, what I -- what we show here is the light blue color line here is a 300-milligram QD dose we used in the Phase III trial have the sustained 24-hour target inhibition. So this has really demonstrated sovleplenib has the best-in-class potential, have sustained the target inhibition and also this clean profile and limited off-target effect and have a better, wider therapeutic window. And here also update you about the drug exposure and safety summary. And the median exposure for the sovleplenib group is 24 weeks versus placebo is 12 weeks, as you recall. If the patients don't have a response with a platelet increase over 50,000, they can actually withdraw from the double-blind period and enter the open-label stage. So we have -- sovleplenib have a longer exposure duration and also the compliance for the 2 groups, placebo and sovleplenib is very similar. Also important on the treatment-emergent adverse event particularly the high-grade AE, the sovleplenib treatment arm with a greater than 3 AE, the placebo and the sovleplenib treatment are very similar. And serious AE is also very similar. And there's a very low discontinuation rate about 3% of the patient for sovleplenib treatment and also the patients with the dose interaction or reduction is about 12%. So in general, the sovleplenib is well tolerated in this ESLIM-01 trial. And also here is the most common TEAEs by PT. And the top one is the upper respiratory tract infection, COVID-19 infection, LDH increase. So as you -- the study enrollment period for the Phase III trial, ESLIM-01 is September 2021 to the end of 2022, which is the later part of the enrollment is really the pandemic exposure for COVID-19 in China. And so the upper respiratory infection, COVID infection is really reflecting that. And so -- and also, I want to mention here the exposure time for sovleplenib on the left panel here, which have a longer duration of exposure, the treatment duration is 24 months -- 24 weeks versus 12 weeks in the placebo. So highlight the EHA results for ESLIM-01. And they met all the primary and secondary key endpoints in this very heavily pretreated patient population. And we are very pleased to see highly robust durable response rate, 48% sovleplenib versus 0 in the placebo group. And also in patients, which is also heavily pretreated with TPO/TPO-RA 75% have been exposed and refractory to the TPO/TPO-RA treatment are equally or very consistent efficacy results observed. And the fast onset after week treatment, the platelet increase already very obvious and also improve the bleeding score and quality of life, including fatigue. So in general, and also I want to mention in previous fostamatinib they have a low GI toxicity observed in the ESLIM-01 trial and less hypertension. And also importantly, while I mentioned here, there is no thromboembolic event has been observed in the ESLIM-01 study because TPO/TPO-RA agents are stimulating the platelet production. And sometimes, they can have an overshoot of the platelet and leading to a higher incidence of thromboembolic event. So this Syk inhibition pathway have another advantage with no thromboembolic event. And so sovleplenib is efficacious and tolerable option for ITP. And also compared with the emerging therapies in development. The FcRn receptor and agonists and also BTK, rilzabrutinib and the other Syk inhibitors, cevidoplenib and also the BAFF inhibitor monoclonal antibody lanalumab. So all these has been reported. If we look at the durable response rate is all better range from the lower end of the fostamatinib, 18% to [ 22% ] to low as 30% for the other new agents. So we are very excited about the data, the 48% durable response rate in the ESLIM-01 trial. And also looking at the primary ITP landscape. So I mentioned that TPO/TPO-RA is predominant as prescribed market share, both globally and also in China. And globally, it reached PROMACTA have over 2 billion treatment sales and NPLATE also over $1 billion status. The 2 agent, TPIAO and Hetrombopag has only available in China. And TAVALISSE, which is fostamatinib also approved in the U.S., Japan and Europe, reached at $94 million sales in 2023, pretty much limited by their less durable response rate in the late-line therapy. So this is the treatment landscape. We think sovleplenib has very unique position, which is going to be an added and murine in this ITP treatment. And also mentioned some of the undesired effect for the existing therapy, for example, eltrombopag hepatic decompensation, liver toxicity, the black box warning and also have a drug-drug interaction, some other effects like cataracts, transaminitis as side effect. Avatrombopag which is a newer TPO agent and also have a risk of blood clotting and could be as high as 7% reported. Romiplostim also have marrow reticulin fiber formation, highly varied platelet count and the pain at administration site. Fostamatinib, as I mentioned before, the GI toxicity and hypertension, which has a limited effect for this prescription. So here's the review article by Dr. Nichola Cooper and Universal London, really mentioned, right, because the feature of the second inhibition without overproducing the platelet overshoot can have maybe a good option for drug to consider for patients with increased thrombotic risk and, for example, coronary artery disease, diabetes and advanced age or obesity. So this is also from the ESLIM-01 trial, we also observed the Syk inhibitor sovleplenib has no reported thrombolytic events. So this could be an advantage compared to TPO-RA. And also, I already mentioned here, this is not a direct head-to-head comparison, it's a cross-trial comparison. I want to mention here. So at least we look at the data, [indiscernible] result, the diarrhea, nausea, hypertension are lower in the sovleplenib treatment group. And so this also could be an effect and also have a lower discontinuation 3% versus 10% for fostamatinib and [ drug interaction rate reduction ] . Also, I mentioned the all the other TPO/TPO-RA treatment, they all reported thromboembolic event, some could be fatal. And we don't see -- we have very low incidence of platelet counts increase over upper-limit normal, reported the ESLIM-01 trial and those no thromboembolic events observed in the ESLIM-01 trial. So other could be another key differentiation for this sovleplenib versus other agent. And also at the EHA on the same day, the oral presentation, the manuscript is published online by the Lancet Hematology. So from marketing perspective, really, we want to look in the key differentiation for sovleplenib. We want to capture the previously treated patients with TPO/TPO-RA with even patients with heavily pretreated patient population, 75% prior refractory to the TPO/TPO-RA treatment, we have seen the similar durable response rate. So this is one of the important strategy for us to consider. And also for patients, as I mentioned, there are a significant portion of the patients have increased thromboembolic event and being target inhibition for Syk without overshooting the platelet and thromboembolic AE. So this is another key advantage for the patient, for the ITP patients. And also, because of high durable response rate and improved quality of life, we can target a patient in the second-line treatment market after glucocorticoid [indiscernible] patients seeking those improvement. And also about 33% of patients with concomitant medication, we can see the dose reduction, the interaction for the concomitant ITP treatment. So this has also demonstrated a good safety and efficacy with the potential combination of glucocorticoid potentially moving to even to earlier line therapy. Also internationally, we have initiated Phase I trial and open to enrollment. And also from a clinical development perspective, there are a few other areas we could consider ESLIM-01 trial in the global setting or a combination with the glucocorticoid and -- or even combination with standard and also for autoimmune disease, significant portion of patients have developed secondary ITP and could potentially be -- other indications could be developed. Here's -- that's the highlight for ITP. And also I want to quickly update you also how we present our clinical proof-of-concept study for a Phase II trial of sovleplenib in the Warm Autoimmune Hemolytic Anemia, wAIHA and a few words about epidemiology and disease. wAIHA occur about 0.8% to 3.0% of 3 per 100,000 patients with a prevalence not above 10 to 20 per 100,000. And it is a predominant form of the AIHA and also it's a high unmet need because the death rate also could be up to 10%. China incidence is about 26,000, global 150,000. Similar mechanistically is very similar to the ITP is the autoimmune antibody, attacked red blood cell and engulfed by the macrophage. So traditional therapy, this is even in the higher unmet need because they're just traditional treatment is the glucocorticoid to treatment anemia. And there is no FDA-approved that's target therapy, Rituxan is commonly used as off-label use, but patients can progress rapidly and also have a very limited treatment option. So similar to ITP, we think that dual inhibition of B-cell producing antibody and also bleb in macrophage eating up the coated -- antibody-coated red blood cell will have a very different treatment for wAIHA. And this has been shown previously in our preclinical animal model study, but now we are very pleased to see our clinical study. These are the primary and secondary wAIHA patients previously treated corticosteroid and is a placebo-controlled study, 3:1 randomization, double-blind phase at 0 to 8 weeks and after 8 weeks, they can go to the open-label stage after 24 weeks. So from a clinical over response rate, we can see the first 8 weeks, we have 43% of patients have a response which define a 100 gram per liter increased hemoglobin and also the 20-gram increase of 220-gram per -- above the baseline level, and the dual response rate is 3 consecutive treatment, meeting that criteria is about 18.8% patients. When they opened the -- finish the open label 8 to 24 weeks, there's additional patients have a clinical response. The overall response rate is 66.7%, overall response rate combined for the 24-week treatment period and durable response rate of 47.6%. And here's the hemoglobin increase, I can see about 4 to 5 weeks after treatment and reached over 100-gram level and sustain the high level. So this is a little bit slower. As you recall, for the ITP, the -- you can see the platelet increase to the normal range at -- after one week. So for the wAIHA, the hemoglobin increase takes a little bit long time, but it's highly sustained for this sovleplenib treatment group is about 71% overall response rate, and it's highly durable. And also in terms of patients who previously treated or without the anti-CD20, Rituxan, the response rate also similar, the sovleplenib is efficacious both on Rituxan treated or untreated patient population. So here's the takeaway highlight for the POC trial. Overall response rate is 67.7%, durable response rate. The overall response rate and 47.6%, durable response rate in the 24 weeks prime period. And even patients crossed over from placebo achieved a similar high response rate. And there are rapid, sustained improvement in hemoglobin level. Stable response over 24 weeks period and 71% durable response for the responder -- durable response for the responder. And so based on this encouraging data, we initiated a Phase III portion of the ESLIM-02 trial. And there's a few words. In other preclinical model, we have seen -- on the left-hand panel here is the rat model for collagen-induced arthritis model. We can see sovleplenib actually, which is the red line here compared with the [indiscernible] 6. There's a decrease at the arthritis and the [indiscernible] swelling as the measurement. And also in the lupus model, we can see sovleplenib treated compared with dexamethasone and the vehicle has sustained over survival, 100% of the murine model actually lived to the 24 weeks. Highlight the sovleplenib data. There's once daily oral dosing, no drug, not affected by the food. And in multiple preclinical model, we show the efficacy really indicating target inhibition for Syk has the potential for multiple autoimmune indication or malignant [indiscernible] and also in combination, not only with the experimental medicine like a BTK in clinical model, we can see the added benefit and also in the clinical trial setting, we can see in the combination with the other ITP treatment, I also see the benefit. So it's because of the low target, off-target toxicity can combine with the other agent and also targeting the root cause of autoimmune disease. And so overall, globally, we already have over 700 patients already treated with Syk inhibitor, and this has been demonstrated highly specific and efficacious agent. We are very pleased at -- for the development of our sovleplenib, our new agent. So I think we can probably skip the break since it's an online event, maybe I can continue to give you an update about the other program. One is surufatinib in the pancreatic ductal adenocarcinoma PDAC development. And the goal is really for our -- approve the product to expand the indication. So the SULANDA, Dr. Su already mentioned, so it's ranked the second brand market in the net, in China. And also, we have reported, actually, the investigator initiative trial reported at the ASCO last year about the first-line combination with PD-1 and chemotherapy. And I'm going to highlight some of the data, top line data and also our clinical development in the first-line PDAC. So pancreatic cancer is represent a huge unmet need -- as China market has about 100,000 incidence with about $1 billion range of the market potential. And globally, the incidence really are reaching over 0.5 million patients. And this is very hard to treat because it's in immunological cold tumor, and this what we call the immune desert because it's highly fibrose -- fibrotic and very limited treatment option, and also because the diagnosis onset -- diagnosis very light early and very small percent of patients actually can do surgery and overall compared with breast cancer, prostate cancer or the other cancer type with a high or 5-year survival rate. Unfortunately, pancreatic cancer patient is less than 13% of the 5-year survival rate. The treatment option is primarily chemotherapy dominated. The first line is either FOLFIRINOX or gemcitabine/Nab-paclitaxel, [ abraxane ]. And overall, the lifespan for this patient is less than a year. First-line treatment with a response rate of 30% -- 20%, 30%, PFS 5 to 6 months, if they progress, they can go to the second-line treatment, but in general, the patients actually have a very short survival rate because it's really the complex and challenging disease etiology with late presentation of the disease, fibrotic and immunosuppressive stroma and resistant -- relative resistance to immunotherapy. Here is the FOLFIRINOX and gemcitabine Abraxane. So GA or AG is what we call, which is the standard frontline therapy. I mentioned about with -- in their clinical trial over existing therapy before the [indiscernible] trial with the median PFS over that 5 to 6 months and over survive 8 to 11 months. So that's kind of the treatment landscape for the first-line therapy. So why we think surufatinib is -- could potentially be important addressing the pancreatic cancer because the mechanism of action is surufatinib is not only inhibitor VEGFR, but also have other targeting agent, for example, CSF1R impacting the tumor-associated macrophage, enhance the T-cell activity against tumor. Here's preclinical data. It's a little bit small if you're on the right-hand side, and you can see the plot here is the patient, the mouse xenograft had fast growth when they use the AG in gemcitabine and Abraxane, have reduced the tumor growth and AG plus surufatinib also reduced tumor growth and AG plus surufatinib PD-1 have the best tumor inhibition. The primary reason we have done further analysis in the AG-pretreated patient or chemotherapy-treated patients, there's increased macrophage, M2 macrophage and [ CSF-1R ] in tumor cells, which will further develop resistance. And also lead to the higher PD-1 [indiscernible] checkpoint inhibitor, immuno checkpoint, PD-1 had the overexpression. So targeting all these feature in combination with PD-1 and surufatinib plus chemo really have good preclinical evidence to block the tumor growth. So in this -- this is the one of the IIT study by Professor [indiscernible], the -- is a dose escalation and expansion study. The primary endpoint is the dose in the toxicity for the dose escalation stage. And then in the randomized phase, Surufatinib plus camrelizumab plus S1 versus AB. So I want to mention here is there is a slight different chemotherapy on, even with the compared chemo arm, the first line is a standard of care, Abraxane plus gemcitabine for the treatment group the chemo is Abraxane plus S1. So it's a little bit different backbone treatment. In the preliminary data reported at ASCO GI earlier this year, the combo arm, the NASCA arm have a 50% of response rate versus AG about 27% of response rate. So the AG is the standard of care. The data for AG is highly consistent with the report of first-line data. And what we really impressed is the NASCA overall response rate reached 50%. And also the median PFS in the NASCA arm also reached 9 months and OS is now mature, but is reported above 13 months at that time data cut off. So versus the standard of care in the first-line setting, PFS 3 to 6 months over 7 to 11 months, the IIT in first-line pancreatic cancer, the NASCA trial -- the NASCA treatment regimen also have a significantly improved PFS and OS, which is highly encouraging. So based on the data, the IIT results, we initiated a Phase II/III trial, camrelizumab and AG and Surufatinib followed by the Surufatinib and camrelizumab maintenance therapy. So the Phase II portion, the primary endpoint is over the response rate and secondary endpoint of PFS because as I mentioned, there is -- for the IIT data because they use S1, we want to use the AG compared with the standard of care. So we just really want to have a quick Phase II portion to verify the IIT data in this combination setting. And then the Phase III with a primary endpoint of overall survival. And the trials really initiated in China. And with the next program, I want to also update you on new program, which is our third-wave product, HMPL-306 is the dual inhibitor for IDH1 and 2, mutate relapse/refractory myeloid leukemia. And so this is -- based on the data we published in EHA last month, we also entered a Phase III trial. So here's the overall AML demographic, the patient demographic and also the market potential. In China, about 20,000 incidents and about $100 million to $200 million market potential. Globally, we see the incidents explode to 200,000 cases. So among these leukemia patient, AML patient, IDH1 or 2 mutations come to 15% to 25% of AML patients. Also, we know just based on the current treatment standard landscape, nearly 25% AML patients fail to achieve remission after treatment. So far, there's really no dual inhibitor for both IDH1, IDH2 approved globally. So one IDH1 is approved in China, two IDH1 inhibitor, and one IDH2 inhibitor approved in the United States. So a few words on the AML is really where the myeloid cell cannot differentiate to normal blood cells and turn into the cancer. And so this is a highly deadly disease and symptomatic, weakness, fever, infection. So these patients is really in a very dire stage. So Isocitrate Dehydrogenase IDH1 and 2 is a key enzyme in the treatment cycle. And so the IDH1 is located in the cytoplasm and IDH2 and 3 located in the mitochondria. And so IDH catalyzes oxidative decarboxylation to form alpha-ketoglutarate during the metabolism and the mutated IDH can lead to the highly carcinogenic 2-HG, 2-hydroxyglutaronic acid and it plays an important role in the etiology of solid tumor and heme malignancy and accumulation of 2-HG causes DNA hyper-methylation and promotes tumorigenesis. So -- and also, importantly, not only IDH1 and 2 is the target for cancer validated drug target, but also the IDH-mutated 1 and 2 isoform switching and lead to the resistance if you inhibit IDH1 mutant, the IDH2 could be activated. So during inhibition of both IDH1 and 2 are very important to prevent isoform switching leading to the drug resistance. And also, the epidemiology, you can see the IDH1 and 2, percent of the patient mutation in varieties of the tumor, solid tumor and heme malignancies, about 60% to 80% at glioma patients, and also secondary glioblastoma, 75% -- 70% of the patient, AML account 15% to 25% and MDS about 10%. The other lymphoma, AITL, about 26%. So in sarcoma, chondrosarcoma, osteosarcoma, cholangiocarcinoma and also giant cell tumors of bone, so also have a kind of a high mutation rate for IDH1 and 2. So it's actually an important target, in both solid and malignant heme. In the preclinical data, here's the HMPL-306, in vitro target inhibition, it can reduce the 2HG production. And the EC50 -- IC50, it is quite similar against IDH1 mutated cell versus the IDH1 inhibitor, Ivosidenib, AG-120, you can see the potency reaching quite comparable nanomolar range. The IDH2 mutant cell lines also has HMPL-306, has a very potent target inhibition. And in some of the IC mutation type also has more important advocacy. Another feature of 306 is highly brain penetrant. On the left side is AG-120, TIBSOVO, the plasma and the brain concentration, drug concentration of the 8 and 24 hour, you can see, it's predominantly still plasma level and the brain concentrate is very low. On the right-hand side is the HMPL-306 50 mg/kg and the brain concentration has -- with the increased exposure time, the brain concentration situation has really reached a higher level. So it's has a potential for neuro tumor indication, for example, glioma and here's the Phase I dose escalation and dose optimization study for HMPL-306 in AML patients starting from 25-milligram QD all the way up to 250 milligram QD. And we also chose 2 expansion dose level at 250 and 150 QD level. From the preclinical data we know, I mean, from the clinical data, we know that 150-milligram dose above is efficacious dose versus both IDH1 or IDH2-mutated patients. We have the -- finally, based on the clinical data for the Phase I, I will explain later, we chose the RP2D dose as 250-milligram QD dose for first cycle followed by the 150-milligram QD from cycle 2 and beyond. This is really helping to reach the -- have a quick loading to reach the status, status days have a higher concentration, reach the stable concentration to allow the -- demonstrate efficacy because the AML patient is very aggressive type of form. So reaching that initial high concentration, high exposure is important to inhibit tumor growth -- cancer growth. The efficacy, we look at the CR and the CRh rate as important clinical parameter because this is widely -- the clinical progress has demonstrated the complete response or CR, with incomplete hematology recovery. It has a good predictor for OS, right? And so this is one chosen. And again, we look at the efficacy and also safety for this study. Here is the top line results for both the efficacious dose during the dose escalation phase and RP2D dose. Here, we can see in -- on the left-hand side is the IDH1 mutated patients, on the right-hand side is IDH2-mutated patients. In the 150 and 250 group, we see CR/CRh rate of about 27% and in the RP2D because of the quick loading and quick time to reach the higher plasma exposure, we also see higher CR/CRh rate, for IDH1 is reaching 45%, and IDH2 mutated patients at 50%. Also quite important because the AML patient could be heterogeneous patient population. So we have observed some patients with the concurrent IDH1 or IDH2 mutation also with the other key driver mutation. For example, FLT3 or KRAS or NRAS mutations. So if we exclude those patients with the co-mutation for FLT3 and RAS we observed RP2D dose has an even higher response rate, right? Because the IDH1 we have 50% CR rate and RP2D for the IDH2 mutated patients had 62% of the CR rate. So this is highly, highly encouraging. And because the dose escalation stage actually have early treatment and RP2D dose has a shorter exposure, but this trend is very -- start to show here with the efficacious dose, 100 full day, but a longer follow-up, we already observed the 13-month median OS for the -- for both the IDH1, IDH2 patients and also the RP2D dose, you can see the trend is quite similar. This is highly encouraging because for the second-line treated patients with IDH1 or 2 mutation, the standard efficacy -- I mean, the life expectancy over survival is above 5 to 6 months. So this is highly encouraging. From the safety perspective, adverse event, the TEAEs shown on the left-hand side, the TRAEs shown on the right-hand side. And the predominant AEs reported as hematology related heme as an event, platelet count decreased, anemia, neutrophil count decreased, but the higher grade level is low, and so general tolerability is very good for 306 as a good safety profile and also I will show some of the comparisons for the other IDH 1 or 2 inhibitor. So overall, here's the summary with the HMPL-306, Phase I AML data compared with the enasidenib is the IDH2 inhibitor, Ivosidenib, IDH1, Olutasidenib IDH1. And also on the right-hand side is the Lilly compound 738, which is also a reported IDH1 and 2 development inhibitor in development. If you look at the -- in the similar indication, if you look at the IDH1 1 or 2 mutated patients in AML at RP2D dose the CR/ CRh rate for the 306 already reached 60% versus 62% in the IDH1 or 2 mutated patients. And other IDH1 or 2 inhibitor, for example, you can see the CR/CRh rate in general is about 20 to 30 range, either versus IDH1 or IDH2. And also from the reported data from Lilly compound, it really show they need a high dose to reach the target inhibition for IDH2 compared with the IDH1. So even though it's reported that dual inhibitor is still predominantly IDH1 inhibitor because the -- in the IDH2 mutated patients, it needs a higher dose to reach that target inhibition. So safety perspective, we see the general profile for toxicity is actually quite manageable compared with some of the other competitor either approved or in development. We can see Ivosidenib has a higher QT-prolongation. And the other inhibitor also have some reported QT prolongation. We haven't observed in the 306 study with QT prolongation. And also in terms of differentiation syndrome, which is also a class effect and some of these differentiation syndrome could be hard to treat and could lead to respiratory failure or sometimes it could be fatal. And so in general, for the 306, we see a relatively lower percentage of patients with differentiation syndrome, with the grade level also is less than grade 4. No grade 4 patient has been observed and also compared with the other compound, the Bilirubin increases also on the lower side and no high-grade grade 3 has been observed compared with some of the other agents had reported liver toxicity and even fatal drug induced liver toxicity. So we believe HMPL-306 has a very competitive clinical profile not only in terms of efficacy, but also the safety. And so here's the summary for the Phase I data reported at EHA. We have -- this compound has a long half life and also we reached sustained target inhibition at both the 150 and 250-milligram QD dose. And we defined RP2D dose with a higher dose to start for the first cycle 250 with the 150-milligram maintenance. And this is -- we show at this dose level has more robust CR/CRh rate. And also this compound has a potential to really inhibiting both IDH1, IDH2 mutation to overcome the resistance from isoform switching. And also, we think the CR/CRh rate is highly robust and OS risk benefit we observed also seen quite long overall survival compared with the standard treatment. Based on this encouraging result, we launched the pivotal Phase III study. The study is already initiated. This is a 2 cohort design, multicenter trial and with the HMPL-306 single agent versus control group, which is Salvage therapy investigator choice either intense chemo regimen, label as a H here or nonintensive chemotherapy labeled with L here. So although it is treated as 2 cohorts, is using the same center because we really want to take advantage for screening the patients with IDH1 or 2 mutation, they can really put into this single trial instead of running 2 separate trials and using the same centers to screen the patients. So we are very excited. This is called a RAPHAEL trial. We're already enrolling, actively enrolling patients. And hopefully, this is an important drug added to our portfolio to have a registration trial started. And also a few words about the overall AML area. So in addition to IDH1 and 2 inhibitors 306, we also have other -- positioned our development for the -- in the AML space. And one of our new compounds entered clinical development is the MENIN inhibitor HMPL-506 in NPM1m mutation or KMT2Ar AML. And so they are in the clinical development stage. And also a few words because for the 306, there are still other indications for example, glioma, cholangiocarcinoma, so could potentially that clinical development path particularly for the glioma, we see high penetration, which has a potential to go to in the brain tumor development. So to highlight our topic of today and for the Surufatinib approved in China, we expanded our indication into the first-line pancreatic cancer development, which is striking a sizable market to have a line product indication expansion. We are very excited, our first innovative compound in the immuno disease area for the Sovleplenib, a highly specific and potent Syk inhibitor already have a successful positive Phase III trial is the one in China. And we also have a global development program. And in China alone, it's addressing a $500 million to $700 million market with -- in patient population, ITP with a higher unmet still existing. In 306, our dual inhibitor for IDH1 and 2 also had demonstrated the best-in-class potential. Currently, there is no globally approved dual inhibitor in the AML with the robust Phase I data really addressing this deadly disease with good market potential. So addressing globally also has a high incidence, has a high unmet need. So with that, I'm going to wrap up our R&D presentation for the 3 key program, and we are open for -- before I go there, just some of the key takeaways for the 3 programs I mentioned here, the Sovleplenib is a first internal discovered best-in-class potential molecule, highly efficacious with 48% durable response rate versus 0 in the placebo and improve the quality of life and also in the wAIHA POP trial, also observed highly robust over response rate, 66.7% over response rate and 47.6% durable response rate. Also in the Surufatinib first-line IIT trial compared with the standard first-line treatment, the median PFS is 9 months, OS 13 months, is highly competitive. So we are continuing the development in this deadly disease indication. And for the 306, the dual inhibitor we have highly encouraging results with over 50% of the CR/CRh rate, which is really exciting data shown. And globally, we have -- we have not yet have any of the IDH1/2 dual inhibitor for AML approved. So this is really addressing the resistance at the front and also highly brain penetrable in the preclinical model will potentially lead to other neuro tumor indication development. So with that, I think we can go to the Q&A stage. Yes, thank you for all your attention.

Thank you very much, Dr. Shi and Dr. Su earlier. We are now going into the Q&A session. But before we begin, just would like to remind everyone on the line that we are already in the blackout period towards our interim results announcement at the end of this month. So for all the materials, which is deemed to be sensitive or financial please forgive us for not being able to share with you in much detail. And then on the presentation, which is already posted on our website, of course, there is the safe harbor statement with the important messages. So please do refer to those for the new information. [Operator Instructions] So either way, it is fine. So maybe I'll just first start off with a question that is already in our mailbox. Well, maybe this one is for Dr. Shi first. I think 2 specific questions. One is regarding amdizalisib. Can the company explain whether it has stopped development when it was already in the registration studies and what are the prospect of this product for HUTCHMED. That's the first question. And then the second question is on Surufatinib that we haven't obtained a development partner yet. And can you elaborate a little bit whether this product is not as good as some of the other similar product available outside China. And is there any risk that similar products to Surufatinib may come to China and impact the prospect of Surufatinib in China. So these 2 questions. Thank you Dr. Shi.

Yes. So first, and as I said, as you recall, right, from our last earnings call, we have indicated, right, the development plan has been discussed and communicated because our original plan was follicular lymphoma third-line development with a single-arm registration trial, we did observe very good clinical activity and safety. And -- but the regulatory environment has quite changed. We have discussed with the MMPA about the registration path using single arm, completed the trial as originally agreed upon. But there -- because of withdrawal of all the PI3K-delta inhibitor, in the global market and also some of the latest data shown, the CD has expressed a concern through the development, they actually require us to run a randomized trial in this setting to demonstrate the safety and efficacy. So from the development landscape and the return on investment, we do see the time line for a randomized trial is going to impact our financial return. So for the -- and amdizalisib, as a company, we have stopped our further development in the FL and the MCL indication because the feedback from CD is really on the randomized trial, so the return investment is really not justified for the -- our original development plan and the time line and the launch time line to really achieve the factor there. So that's the status for amdizalisib. For surufatinib, it is also kind of a little bit unfortunate decision, last year, the year before we announced with -- for the neuroendocrine tumor NDA, we withdraw the application in the U.S. and EU because the original development plan, even through the discussion with the regulatory agency, the original plan was really using the SANET-ep and SANET-p, the China Phase III trial, along with the bridging study to support EU and the U.S. registration even though at the initial stage, the discussion was the potential. But later on, it was really the response. We've got a CRL. So it's not reflecting -- the comment is really now reflecting the global kind of patient population. So this is kind of communicated with the outside world. So for -- but the registration, I think for -- in terms of your question for China, right, we are already a leading product, second market leading product in endocrine tumor space. And it's very robust. So I know there are a few compounds like PRRT and some of other is in development and registration. But in terms of the -- in China market, we still think surufatinib is a very competitive product, and we have good product and familiarity from physicians. So with all the data, we think we have a very good marketing and the strategy to defend our market. Globally, I think because the landscape changed, right, for neuroendocrine tumor, there's a PRRT and other products already in the second line kind of neuroendocrine tumor. So the landscape has changed very rapidly. So in turn, the BD and the global development, we're really thinking about the other indication, right, such as the case for -- we presented here, where the combination of VEGF and CS1R activity for surufatinib addressing other indication still has a potential for the global development.

Thank you, Dr. Shi. We see a couple of analysts online that have raised their hand. So the first question, let's go to Clara Dong of Jefferies. Clara, you can ask your question now.

Great presentation. This is Clara on for Kelly from Jefferies. So one quick question for sulfatinib and ITP. Can you give us a quick update on your commercial preparation of launching in China, given it's your first commercial launch in autoimmune? And I think last time you also mentioned you scheduled an FDA meeting to talk about the regulatory path for ITP. Could you give us an update on this? And what kind of data you need to see in Phase I those escalations to support you to go forward to pivotal trial?

Yes. Thank you. So for -- I'll address this commercial part first briefly and then get turned to Dr. Su, right. So I think we are building our internal marketing team. So we are well prepared to -- for the heme marketing, even traditionally, we are on the solid tumor side. But from -- we have done very good market research and brand strategy. So I think internally, HUTCHMED is very good. We intend to build our commercial team to launch the product. For -- in terms of global development, as I mentioned, the Phase I trial, the dose optimization study has already discussed with the FDA and agreed upon with the FDA. So we already initiated this trial and is open for enrollment. And global development, I think once this dose optimization is completed, there are multiple potential we can -- there are multiple clinical development paths we can go through to really expand to the global patient population. So I don't know Dr. Su maybe can also address -- has some comments for this question.

Yes, sure. I mean in terms of commercialization in China, as Mike kind of alluded to already, we are building a heme team that will include both benign and also malignant heme indications, sovleplenib, the first product to be launched in China. So we're preparing both on the marketing side and also the sales side as well to support the launch of sovleplenib, the first indication ITP, obviously, potentially, [indiscernible] had to follow in the future and potentially additional nonheme indication, autoimmune disease for that matter. However, this -- the initial indications, ITP and wAIHA, these belong to the benign heme and in China, oftentimes, they are in the same department in the hospital. So at the same time, we are also building up our malignant heme as well because we already submitted NDA in China for follicular lymphoma, and we expect approval sometime next year. So slowly, you saw coming to market. And ultimately, we'll have a solid tumor team as well as a heme team basically covering both benign and also malignant heme indications.

Thank you. Next question goes to [ Carlo ] of Goldman Sachs. [ Carlo ], you can ask your questions now.

I guess we had a couple of quick questions on sovleplenib and then one quick one on savolitinib. So I guess on sovleplenib. One, like if you could add any additional color on your expectations regarding the timeline of the ex China ITP trial and when you might move on to a registrational trial there? And then two, how do you think about the timing of the potential approval in China? And do you expect to be included on the NRDL list given that we understand from our understanding that if the drug is approved too late in the year, it may not be included on the January list until 2026. And then quickly on SAVANNAH. I'm just wondering if you could maybe have framed expectations on what you expect from that later this year? And how quickly you expect to file for -- or you expect for your partners to file for approval in the U.S.?

Okay. So let me comment first on the Phase I trial, right? And we are intending to do the dose escalation and -- for the global trial. So my anticipation is that we can complete it this year. And the dose optimization, we are still working because I think we have a lot of PK/PD data and also in the China and the western patient population. So we are hoping, right, with the dose, we can have the dose defined shortly, even some of these future registration trial will potentially be launched sooner with building those optimization into the Phase III trial -- Phase II/III trial setting to accelerate the development. And so this is kind of the global development. And I also mentioned there are a lot of opportunity for us. I mean finding the right doses, but the western patient population is an important first step. We think -- I kind of alluded to, there are quite a few clinical development area we can tap into. The traditional ESLIM-01 trial or even a combination even in the earlier line even in the secondary ITP. So there are a lot of -- and wAIHA, right? So a lot of opportunity exist. So once we define the dose, I think multiple area, we can get into the global development stage. So that's kind of the sovleplenib. And there are a few other questions, right, for the final approval, I think also, we have the breakthrough destination also under priority review in NMPA. So we think our anticipated timeline is later this year for the approval for ITP indication. I think for -- maybe I think I stop here, maybe I see if Dr. Su can also have some comments first.