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Hello, and welcome to the 2026 interim financial results. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question and answer session. Also, as a reminder, this conference is being recorded. If you have any objections, please disconnect at this time. With that, I would like to turn the call over to Sumedh Neni. You may begin.

Thank you, operator, and good morning, everyone. Thank you for joining today. Welcome to Ascentage Pharma's 2026 interim results and business update call. I'm Sumedh Sunkaraneni, Director of Investor Relations and Corporate Strategy at Ascentage. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions. These statements involve risks and uncertainties, and actual results may differ materially. For discussion of these risks, please refer to our disclosures. Joining me today are Dr. Dajun Yang, our Chairman and Chief Executive Officer, Dr. Faiçal Miyara, our Chief Business Officer, Mr. Jim Ziegler, our Chief Commercial Officer, Dr. Yifan Zhai, our Chief Medical Officer, and Dr. Veet Misra, our Chief Financial Officer. Yesterday, we issued a press release with our unaudited financial results for the six months ending June 30, 2026.

That release and the slide presentation accompanying this call are available in the investor relations section of our website. Turning to our agenda, Dr. Yang will open with a business update, and we will hear briefly from Dr. Miyara and Mr. Ziegler on the business development and commercial priorities behind our global hematology franchise. Dr. Yang will then cover our R&D highlights, and Dr. Misra will review the financials. Dr. Zhai will also join us for part of the Q&A session. We will then open the line for your questions. I'd now like to turn the call over to our CEO, Dr. Dajun Yang. Dr. Yang, you may begin.

Thank you, Sumedh, and thank you all for joining us. The first half of 2026 advanced a single objective, building Ascentage into a leading global, fully integrated hematology oncology company. We are a company that discovers, develops, conducts global clinical trials, and now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide. We are currently advancing nine global registrational trials, four of which are cleared by both the FDA and the EMA. The total revenue grew to $44.5 million, up 29% year-over-year, of which were product sales of $41.6 million on a constant exchange rate basis. And we are reaffirming cash runway through the end of 2027. Importantly, and playing a role to achieving our global strategic objectives, we strengthened our leadership with the appointments of Dr. Faiçal as Chief Business Officer and Mr. Jim Ziegler as the Chief Commercial Officer.

Both are with us today and will be sharing preliminary results. Let's just look at the next slide. This slide, we have two approved products and a late-stage pipeline that's highly de-risked. Olverembatinib, our third-generation BCR-ABL inhibitor, has been approved CML-CP in China since 2021. Tens of thousands of patients have been treated today. The longest patient on our drug has been near almost 10 years now. We have real-world long-term safety and efficacy data that really few companies at our stage can point to. We also have global registration trials, including FDA and EMA cleared, that are ongoing. Our plan is to commercialize olverembatinib in the U.S. and the major pharma markets. Lisaftoclax, our selective Bcl-2 inhibitor, is approved as a single agent in post-BTK CLL/SLL. Globally, we are the second selective Bcl-2 inhibitor to reach the market after decades have passed.

However, in the single-agent post-BTK CLL, we are actually the first to get approved to the market. Lisaftoclax has a unique daily dosing up. We are the only one approved with that label. Enhanced safety and as well as drug-drug interaction observed to date is much reduced compared to other Bcl-2 inhibitors. It also has FDA and EMA-cleared global registration trials, GLORA and GLORA-4. Behind those two, we also have five additional clinical-stage assets all conducting trials in U.S. and China and the rest of world. APG-2449 is a triple kinase inhibitor covering FAK, ALK, ROS1. The MDM2 inhibitor APG-115, and also targeting both Bcl-2 and Bcl-xL APG-1252, and the EED inhibitor APG-5918.

Also the newer one joining this year to the U.S. and China phase I trial is the APG-3288 BTK degrader. In light of our mission to build Ascentage into a leading global hematology/oncology company, we have strengthened our leadership team in the two areas that determine whether franchise reaches patients outside China: global business development and commercialization. I'm really pleased to welcome Dr. Faiçal Miyara as our Chief Business Officer and Mr. Jim Ziegler as our Chief Commercial Officer. Both bring deep experience directly relevant to the next stage of Ascentage's growth. I would like to give each of them a moment to introduce themselves and share what attracted them to Ascentage. Faiçal, let me turn it over to you.

Thank you, Dr. Yang. My name is Faiçal Miyara. I'm the current Global Chief Business Officer at Ascentage. I have 20+ years in oncology business development, social evaluation, and I also was involved in venture investing across leading pharmaceutical industry. I was in, as you see in the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen, as well as mid-size biotech like Kadmon and IO Biotech. I was also instrumental in the deal or the M&A that happened between Kadmon and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executed teams at IO Biotech and Ipsen. When I was at Eli Lilly, I advanced ERBITUX and CYRAMZA as a lead oncology product or antibodies, and co-initiated the Pfizer Centers for Therapeutic Innovation. So I'm very, very pleased to join this very, very good team at Ascentage. We'll talk about our pipeline.

It is very, very outstanding. With that, I will leave it to Jim to give you some information on the Chief Commercial Officer.

Thank you, Faiçal, and good morning, everyone. I am also very pleased to join the Ascentage team. I have spent more than 25 years building and leading commercial organizations with broad experience in hematology, oncology, and specialty products across both large-cap and small-cap biopharmaceutical companies. What attracted me to Ascentage is the opportunity to take a deep, late-stage hematology/oncology portfolio with two already approved products, and help translate this clinical foundation into a global commercial organization. My immediate focus is on building the foundation for potential commercialization of our products, including commercial strategy, market access, and associated capabilities we will need as our registrational programs advance in the U.S. and other key markets. I look forward to providing updates on our progress over time. I will now turn the call back to Dajun.

Thank you both. Let us look at the R&D highlights. Our development strategy is the engine for full global commercialization strategy. Two approved hematology asset anchor it, and everything behind them is designed to add to our best-in-class portfolio. Turning first to lisaftoclax, our cornerstone asset. Lisaftoclax was approved in July last year for the treatment of adult patients with CLL/SLL who have previously received at least one set of therapy, including BTK inhibitors. Actually, we conduct the registration trial for the patients who have failed BTK inhibitors. For that indication, we are actually global first one. More importantly, we are running four global registration trials, two of them cleared by FDA and EMA, each of them will have a transformative therapy globally. I think the most important one among the four registration trials for the global strategy is the GLORA-4.

In the frontline, high-risk MDS evaluates lisaftoclax in combination with azacitidine versus azacitidine alone. This has been cleared by FDA, EMA, China CDE, and also PMDA in close to 20 countries. Let me also highlight a few key differentiation with two other currently on the market, Bcl-2 inhibitors. As you can see, the lisaftoclax was the only one designed with daily dose ramp-up in the beginning, and the only one approved with only three dose strengths and five daily dose ramp-ups planned, and then reached the target dose, 600 mg, and continue. As you can see, the venetoclax was first approved about 10 years ago, has a five-week dose ramp-up. The other one just approved, sonrotoclax, early this year, with the five-week dosing. I mean, the weekly dose ramp-up by the nine dose cohorts, okay?

Because lisaftoclax started with 1 mg. Initially in the trials, it was nine weeks. I think they combined two into one week. So each week they have do the ramp-up 2x and then total nine dose levels to reach a target dose. I think that is very important for the patients with the CLL/SLL, the convenience and also reduce the time of hospitalization. Let us also look at the summary of favorable safety profiles and the better drug combinability. We try to compare in the same setting, same patient population, but also be clear, this is not a head-to-head comparison. But if we look at the overall, the safety profile in terms of infection and the PK variabilities, lisaftoclax is probably the best one among the three. If we look at the SAE incidence, lisaftoclax also much lower and no drug-related death reported to date.

In the PK variability, I think the other two are strong, the only three or four inhibitors, and we show minimum fluctuation in plasma concentration compared to other two. I think also no dose adjustment required, compared to the other two in terms of DDI issue. I think for the chronic dosing patient, like many hematology malignancies, safety and tolerance and the drug-drug interaction risk are important differentiation. Let us also look at the key data in the U.S. trials. In the MDS, lisaftoclax as decided in frontline produced overall response rate 80% and 50% in relapse R/R MDS patient. More importantly, we have a 40% CR rate. The time to response also very short. Here we also highlight two representative real-world cases in high-risk MDS, since it was launched last year in China.

In the first case, a 71-year-old patient achieved CR after two cycles with a rapid hematological recovery. In the second case, a patient with a poor response and failed venetoclax and then achieved the CRI within just 14 days after switching from venetoclax. These cases provide encouraging indications of clinical activity, including patients previously exposed to venetoclax. Let us also look at the AML case. The overall CR/CRI rate was 72%, with a 61% MRD negative rate. Response was 100% with patients with NPM1 mutation and 83% in the IDH2 mutation. I think it is important all those trials actually with the patient in U.S. and Australia. This is not the clinical data from China. As we previously indicated, in the case of patient who failed the venetoclax, which is truly a medical need globally, we still see a 31.8% overall response rate with no cases of tumor lysis syndrome.

Same target, same pathway, lisaftoclax remains active. I think at least based on the current clinical data of the resistance to Bcl-2 inhibitor, majority are not due to new mutations, but MCL1 upregulation and some also with the Bcl-xL upregulation. So I think that explain partially why the same AML patient failed venetoclax, lisaftoclax can still achieve activity. So I think that those reflects a key differentiation in the downstream resistance profile and represent meaningful clinical opportunity. But of course, more importantly, with the better safety profile and the lower risk of DDI, also provide more opportunity for combination. In our case, combination with olverembatinib would overcome venetoclax resistance in AML. Turning to the second pillar of product strategy, olverembatinib.

I also want to highlight why we believe this can be a best-in-class third-generation BCR-ABL inhibitor to patients with CML in the second line or late settings. This has already been approved and highly de-risked asset with several years of clinical and real-world use in China. We receive a validation from Takeda as they hold exclusive option to license olverembatinib outside Greater China and certain other territories. This was entered with Takeda about two years ago. Globally, the most important study for the CML is the POLARIS-2. Part A enroll chronic phase who has received at least two prior TKI randomized olverembatinib against bosutinib. This is clear by FDA and EMA, and there is also Part B, which evaluate olverembatinib in patients with T315I mutation. As you know, bosutinib does not have activity, so that is the single-arm trial.

You can see, this is a difficult second-line patient population, which we believe olverembatinib can be most differentiated. Besides the CML, olverembatinib also have a strong activity in Ph-positive ALL. So POLARIS-1 is also important. This is our global phase III study in newly diagnosed Ph-positive ALL. Again, both cleared by FDA, EMA, and CDE, and also with breakthrough therapy designation in China. We have already shown strong Part A data at ASH as oral presentation last year, and we continue to advance the global study. Let us look at some of the important bridging study, led by Dr. Elias Jabbour at MD Anderson. This actually was conducted four or five years ago. Dr. Elias Jabbour, as you know, is a leading investigator in CML and also Ph-positive ALL. In this particular study, we enroll 62 heavily pre-treated CML-CP patients.

More than half have received at least four prior TKI. They are like fourth or fifth line, and half of them have received the ponatinib, and a third of them have T315I mutation. I think with this really poor baseline patient population, we achieved the MMR as a single agent, 42.9% in ponatinib-resistant patients, 33% in asciminib-resistant patients, and more importantly, 27% in patients who failed both ponatinib and asciminib. Basically, those are the patients with no other options. But single agent olverembatinib have a pretty good efficacy. I think that this treatment, again, strengths the overall differentiation and the clinical efficacy versus ponatinib and asciminib. Also we have a pretty long-term safety profile. In China, the longest patient have been using olverembatinib almost 10 years, since October 2016.

In this particular patient trial, the longest patient treated in the U.S. is over three years with a manageable safety profile. Let us turn to slide 16. I want to show some more recent data. I think one case is the second-line trial strategy. Olverembatinib demonstrated 47.6% MMR rate as a single agent. More importantly, the new data, just in this year reported, in a prospective controlled data, in the second line or late-line setting, showing a clear benefit from switching to olverembatinib, a type of evidence that remains uncommon in this patient population. I think the differentiation you can see is very dramatic, right? So if they do not switch to the best-in-class potential olverembatinib, the MMR rate remain only 10%. I think that is a huge benefit in terms of for the patients in the late-line CML. Those patients actually have been treated with at least two TKI.

Some of those also with asciminib. Olverembatinib delivered six months MMR rate 54%, and then even higher at 57% in 12 months. Those who did not switch remain only low 20% response. I think, as you can see, this is a huge benefit for patients if they switch to the olverembatinib. Also important safety profile in terms of AEs. Let's turn into slide 17. I think that the benchmark is important because the landmark changed over the last two years. I think in addition to at least two years ago, the only competitive product we consider is the asciminib, but now there is two drug TERN-701 and ELVN-001 in the study in the U.S.

But first, I think the most important one, we are the only one have long-term evidence, the other program does not yet have as those are still in the phase I or early phase II, and we have six years follow-up for patients who are in the second line, and 10 years for the first line, the phase I trial. We are the only one have controlled the comparative data set. Those are new requirement from FDA in terms of Project Optimus. So you have to run the RCT trial in order to get the NDA approved. Another important differentiation in the CML patient population is really the baseline, right? So you can see the patient treated with olverembatinib are more late-line, heavily pretreated, and also with the mutations.

I think those data clearly demonstrated olverembatinib as the potential drug of choice in the second line of CML after patient who failed the most advanced available TKI. I think I will show you a few more study in the control in more details on the next slide. Slide 18 is a real-world analysis of 69 blast crisis CML patient who went on transplant, and 26 was treated with olverembatinib, and 43 with first and the second generation TKI. So the olverembatinib group entered transplant in deeper molecular remission. MMR rate 53.8% versus only 16%, and the CMR rate 23 versus 4.7%. The olverembatinib also have more favorable survival outcome, one year overall survival of 89% versus 71%, and the no relapse mortality 11% versus 23%. These are the two separate patient cohorts in a retrospective real world analysis, not a randomized comparison.

But again, demonstrate important differentiation of olverembatinib in large patient population, on how to treat CML patients. Let's also take a look at the combination strategy. In the patient in the POLARIS-1, with low intensity chemotherapy in front line. I think that the POLARIS-1, three key important differentiation, the data. One, this is front line newly diagnosed Ph-positive ALL. In most cases around the world, chemotherapy is still required because of the aggressiveness nature of the Ph-positive ALL. In the registration trial design, we conduct the Part A, with the low intensity chemo. As you can see, this demonstrate MRD negative CR rate about 63%. This is almost double the ponatinib in the same patient population, the PhALLCON trial, about 34%. Of course, in the trial data, the imatinib only 17%, dasatinib is only about 20%+.

So this clearly demonstrate, in the registration trial setting, olverembatinib is the best among the current treatment option. We also try to enter the chemo-free registration trial. Currently, we have data from the oral report at the ASCO, by Dr. Elias Jabbour around MD Anderson, demonstrate that if we combine with the blinatumomab, we can achieve 80% MRD negative rate, and a 91% CR/CRI. We also demonstrate importantly in the pediatric R/R Ph-positive ALL patients. Actually, those data have been available, reported first time two years ago. We continue see benefit of safety and overall response. I think very impressively, we achieve 89% overall response rate after cycle two, day 15, and the overall complete response in an oral chemo-free regimen. I think that this combination data is key because this is two orally active agent, chemo-free, in the pediatric ALL setting.

Moving on to the APG-115, another asset in our portfolio, small molecule targeting MDM2-p53. It actually holds six FDA ODD, and two rare pediatric disease designation. This actually has been conducted in our portfolio for a while, as there's no approved product yet globally, targeting the MDM2-p53, as MDM2-p53 is one of the most important tumor suppressor gene. But I think that you do see some recent progress that Ipsen acquired Kartos MDM2 inhibitor, and with actually pretty decent $450 million up front and up to $1.75 billion, including milestones for our phase III program in myelofibrosis. I think that there is a probably potential for the MDM2-p53 inhibitor combined with a JAK inhibitor in that actually trial as an add-on strategy. I think that data is encouraging. We are also currently do that trial with MF patients. So again, this remain wholly owned by us.

In the ASCO, we present encouraging data for APG-115 in combination with the lisaftoclax in the pediatric soft tissue sarcoma patients. Globally, pediatric rhabdomyosarcoma and other soft tissue sarcomas are truly a medical need. In that setting, we demonstrate good combination safety and impressive 23.5% response rate and also 70% disease control rate. I think that those encouraging data in the clinic demonstrate the already active agent from Ascentage. I think in the interest of time, I try to focus on mostly the key data. Here's a slide to show you that the cornerstone asset of a Bcl-2 inhibitor lisaftoclax combinability with three other targeted small agent all are already active. I think we all know, as mentioned, that the main reason for Bcl-2 resistance is the upregulation of Mcl-1. So we have demonstrated olverembatinib actually can indirectly down-regulate Mcl-1.

We not only have preclinical data, but now have clinical data to demonstrate that combination of the olverembatinib with lisaftoclax can show the synergy, more importantly, not just the CML or Ph-positive ALL, but the patient with AML or MDS and the Ph-negative ALL. Especially for those patients who fail the venetoclax in the AML, we have clinical data to demonstrate that in addition to what we showed before in the Ph-positive ALL. Again, with MDM2-p53 inhibitor APG-115, now we have clinical data to demonstrate the safety efficacy, especially in those hard-to-treat soft tissue sarcoma patients. We are also moving into the DLBCL, AML, and MF. Part of the MOA for this combination is the synthetic lethality. Again, we are the only company worldwide have all three assets wholly owned by Ascentage.

In the interest of time, I do not have much data to show, but I can tell you that our BTK degrader, APG-3288, have advanced well in the phase I setting in both the U.S. and China across the B cell malignancies who previously exposed the BTK inhibitors. I think we can stay tuned for the progress for both the oncology and the non-oncology indications with the BTK degrader. I think that is all the highlight of our R&D. Let me turn the call over to our CFO, Dr. Veet Misra, for the review of our financial result. Veet?

Great. Thank you, Dr. Yang. Good morning, everyone. Turning to our financial results, the first half of 2026 was another period of continued commercial growth and investment behind our global development programs. Total revenue was $44.5 million, compared to $32.6 million in the first half of 2025, representing an increase of $11.9 million or 29.3% on a constant exchange rate basis. Product sales growth has been our main driver, as indicated by $41.6 million of product sales compromising our total revenues. During the first half, we continued to expand our commercial reach and invest behind both products while maintaining a disciplined approach to managing OpEx and supporting our, and advancing our global clinical programs. Research and development expenses were $102.8 million, compared to $73.8 million in the first half of 2025, representing an increase of $29 million or 32% on a constant exchange basis.

As planned, this was our expenditure, to execute on our high priority to advance enrollment in multiple global registration trials. Selling and distribution expenses were $33.4 million, compared with $19.2 million in the first half of 2025, representing an increase of $14.2 million or 64.3% increase. This was driven by marketing and commercial investment behind our products. Administration expenses were $17.5 million, compared to $13.9 million in the same period last year primarily due to RSU expense. Turning to our balance sheet. We are pleased to report cash balances were $279.4 million as of June 30th, 2026, as well as reaffirming our cash guidance runway through 2027, as we have said before. This funds us through multiple key registrational studies ongoing globally.

To emphasize, we are funding nine registrational programs and are currently taking initial steps to building a commercial organization in the U.S., and remain on target for investments required at the appropriate time to fulfill our global strategic objectives. Thank you. With that, I will turn back the call to Dajun for his closing remarks. Dr. Yang?

Great. Thank you, Veet. I think that with the overall R&D highlight and the financial update, as you can see our last slide, to show we have seven active products in the clinic, with two of them already landed, approved in China. But more importantly, with these already active target agent, we cover all majority of Heme malignancies, from the CLL/ALL to the CML, AML, MDS, and also with clinical activities in potentially multiple myeloma and the DLBCL. I think moving forward, our goal is to focus on the current global registration trials and reach to the NDA stage and build a strong commercialization team outside China as well. To become a global player in the Heme malignancies globally. I think that's all for the brief update with the key data and the financial results. Thank you all for joining us, and also our team.

I think now we are open for the Q&A.

Thank you. At this time, if you would like to ask a question, please click on the Raise Hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, you will receive a message on your screen from the host allowing you to talk, and then you will hear your name called. Please accept, unmute your audio and ask your question. We will wait one moment to allow the queue to form. Our first question will come from the line of Brian Cheng with JPMorgan. Please unmute your line and ask your question.

Hey, guys. Thanks for taking our questions this morning. Faiçal and Jim, welcome to the team. Just to start off, in China, can you talk about how we should think about the NRDL listing for specifically lisaftoclax later this year? Can you talk a little bit about what's the progress that you have been seeing in China, and how should we think about the next updates related to the NRDL listing? Then we have a couple follow-up. Thank you.

Thank you, Brian. A very good question. Lisaftoclax was approved in China July last year. We are the first domestic Bcl-2 inhibitor approved in China. We are the only one, the first one, approved in terms of post-BTK R/R CLL/SLL patients in the registration trial. That was a tough trial, but we demonstrated good safety efficacy. We clearly show the differentiation versus venetoclax or sonrotoclax in terms of the only approved daily dose turn up with a clear safety profile and a lower risk of DDI. I think if you are looking not just at clinical data, but the NRDL reimbursement, less hospitalization, less risk, and also convenience are all important favorable factors for the NRDL consideration. I think currently as update, we have passed the initial review. We are on the final product list for the NRDL expert review right now.

This year, the timeline is actually a little bit ahead of previous timeline. As currently, there are two groups, NRDL experts, officials, and those health economics experts are conducting the meetings, reviews right now. We may call up to a meeting with the experts later this month or early September. Then with the final, we are very confident we will get NRDL coverage for these indications in China. The concern we have or worry is working with the expert is the final price. Of course, venetoclax is already covered for different indication AML in China. It is probably a benchmark. I think we are confident we will have coverage for this indication.

Which is important in China, that NRDL is not just a reimbursement, but the ticket to enter the hospital. Majority of hospital in China rely on the NRDL approval to enter the hospital in terms of a prescription. In case of a CLL/SLL, this is chronic dosing patients. Reimbursement by NRDL means that they can reduce their out-of-pocket payment by the average two third, 60%-70%. In certain regions, the NRDL coverage can up to 90%, so I think that is a huge benefit to the patients in chronic leukemia setting.

Great. Maybe just also turning into your ongoing clinical studies. Curious if you can talk about what is going on with POLARIS-1 and GLORA trials, specifically how is enrollment looking like, and just any sense of how we should think about the timing of the next data readout, and potential pathway to NDA filing. How should we think about the timing of those milestones?

I think for those question, maybe we have our CMO, Dr. Zhai, on the call. Maybe Dr. Zhai can give some answer first. Dr. Zhai?

Sorry, Brian. Regarding GLORA-4 study, right? Sorry, I thought you addressed somebody else's question. Could you—

Yeah.

—repeat the question?

No problem. Yeah, no, just curious how the enrollment is going in the global studies like POLARIS-1 and also the GLORA studies for lisaftoclax. How's enrollment going, and do you have a better sense of when we are going to get the final data cut, to file for the NDA?

Regarding all those global registrational trials, the team worked very hard and tried to complete their enrollment as soon as possible. It is still under the plan. In particular, the GLORA-4 study perhaps is under the radar and everybody paid particular attention to that global registrational trial. Regarding GLORA-2, GLORA-3, and Dajun actually already announced yesterday we already completed the enrollment. For GLORA-2, I am waiting for the data review to mature. GLORA-3 also very close, and the remaining, we plan to complete the enrollment either by the end of this year or early next year.

Great. Thank you.

Let me add a few points to what Yifan said. We have said yesterday in the Hong Kong call that we completed the enrollment for the GLORA-2, which is frontline CLL/SLL setting, combination with other setting and with fixed duration. Of course, that one is not with the FDA, because the control arm is the chemo immunotherapy. That is also over 400 patient enrollment demonstrate our capability in the clinical operation. GLORA-3 is the AML combo with azacitidine versus azacitidine alone. We are in the final stage to closing the enrollment. The GLORA-4, obviously, in the high-risk MDS, many people are watching closely. I think there are a few key points also important to share. One is, this is the frontline. The frontline patient with high-risk MDS. In the trial design, similar to the VERONA, the combo with azacitidine, versus azacitidine alone.

This has been cleared by FDA, EMA, PMDA, and China. Globally, not because venetoclax failed, but also another Bcl-2 inhibitor, venetoclax, is not on the MDS, not on the registration trial. Globally, we are the only phase III registration trial for the high-risk MDS. There is no target drug approved in the high-risk MDS in the last 20 years. This remains globally a mathematical need, and enrollment is doing well because experts around the world in MDS are really enthusiastic, all want to help patients with high-risk MDS. Overall, I think to summarize, we anticipate, as we said before, the enrollment for GLORA-4 and the POLARIS-1, POLARIS-2 could complete by late this year or early next year. The good problem to have, we are looking for potentially three NDA to file the second half of next year.

Great, and if I can squeeze one more in. Just for the BTK degrader, APG-3288, do you have a sense of what you want to see from the early data cut so that investors can make a good comparison against other BTK degraders? Do you have an internal benchmark of efficacy early on? Thanks for taking our questions today.

Yeah, I think we all know that the BTK as a target is very competitive, very crowded, and there are many inhibitors, covalent, non-covalent on the market, and some are doing very well. But the BTK degrader does have an advantage, at least with some of the current up to even Phase III data. We conducted carefully preclinical data to show our drug APG-3288 versus other two from Nurix or BeiGene that have better selectivity and stronger efficacy. But that, again, is in the preclinical setting. Currently, I think in the phase I, we are moving along very well in terms of dose escalation for safety. But more importantly, first, those are all BTK-exposed patients. Doesn't matter covalent or non-covalent, and we want to show some response in those patient population first, right? That is important. That is the key differentiation for the degrader.

Second, we probably will take some patient population, the indications that currently BTK inhibitor is not very active. Some more so importantly, combination with our Bcl-2 inhibitor. I think one example in that setting may be the DLBCL, because so far the BTK inhibitor has not shown good activity as a single agent in that DLBCL setting. And of course, there are also a lot of data that combined with the Bcl-2 may have better readout in this patient population. Another potential one, but we do not have data to share yet, is in the non-oncology indication. I think that there are many autoimmune indications could be benefited with the BTK degrader.

Great, thank you, Dajun, and congrats on the progress.

Thank you.

Your next question will come from the line of Biren Amin with Piper Sandler. Please unmute your line and ask your question.

Yeah. Hi, team. Thanks for taking my questions. Maybe if I could just start with the POLARIS-1 and POLARIS-2 trials. Can you just provide us with an update in terms of when we can expect data from both studies?

Again, for that question, Yifan, our CMO, can address first.

Oh, we just addressed the same question. Let me repeat it. Currently we are very actively enrolling patients and plan to complete the enrollment either by the end of this year or early next year. We plan to submit the NDA next year.

Yeah, I think that they just added a little bit. For the POLARIS-2, the filing NDA is six months MMR rate after the last patient in. We already demonstrated very strong data in the MMR rate for this patient population, and we are confident on that. The key, of course, is finishing enrollment. For the POLARIS-1, the filing of NDA with FDA is the three months MRD negative CR rate. I think, again, the target enrollment is on track. With these six months or three months endpoint for the NDA filing, we are looking for potential filing of those two NDAs second half of next year.

Great, and maybe just follow up on a couple of questions. For olverembatinib, when could we expect to see Takeda make a decision on its option on the license? That is the first question on the global license. Second, as it relates to China specifically, where are you as it relates to achieving access to 2,000 hospitals in China? I think that was a target that was previously set by the company. Maybe a question on the BTK with APG-3288. Could we see first data at ASH this year, and are you planning to evaluate also in the MS setting?

Maybe I will answer your last question first. The APG-3288 is still ongoing in the phase I trial, U.S., China. I think because this is dose escalation and the cutoff for the ASH already ended, we do not anticipate to present the phase I data this year at ASH. The progress is doing well. Perhaps we can have some to share maybe EHA next year in terms of timing for the phase I data. Again, we are conducting several autoimmune indications demonstrating good preclinical activities. Because the non-oncology trials in the phase I health volunteer, you do need a placebo control, right? That is where we are working with to getting IND filed for the non-oncology indications, including the MS. That data will come from a little bit behind because of making the placebo control.

We do anticipate the IND to be filed soon with the autoimmune indications. For your first question, I think the Takeda deal, as you know, we entered the global exclusive partnership option agreement two years ago, 2024. That is again exclusive global outside China and some territories. For that, Takeda, back two years ago, paid $100 million upfront and $75 million equity investment. There is also a total up to $1.2 billion aggregate when they exercise the option and a certain milestone payment. Also they tier the royalty rate from 12% to start, up to 19%. I think globally, Takeda is a key player in the CML and ALL, after Novartis, obviously. I think we do believe Takeda is an important and a global partner for commercialization of olverembatinib.

One of the main reason for the option agreement is obviously they have a competitive product, ponatinib, and the potential antitrust issue. ponatinib patent will expire early next year. I think that is the key component in the option exercises. Also we do work closely since the option agreement signed with the Takeda team. We are actually working closely together to advance all the enrollment and a lot of KOL reaches and planning for the commercialization. With Jim on board, we do looking forward working together ahead of the launch with the Takeda team for the great potential of olverembatinib in the global market. I think you have one more question about the hospital, right? I think currently we are doing well in terms of getting the hospital covered.

I mean, still have a second half of time to report, but we are on the track currently bring the total commercial team about 300, and the goal is to build close to 400 commercial forces in China. I think it is not just the number 400 staff in the commercial team, but more importantly is to cover 80% of the market potential with the two product in China. I think that is where the 2,000 hospitals number we try to achieve. We are on the track to achieve that with the expanding the commercial team and also the leadership, both in U.S. and China.

Great. Thank you.

Thank you.

Your next question will come from the line of Jeet Mukherjee with U.S. Bancorp BTIG. Go ahead with your question.

Great. Thank you for taking the question. Maybe just to dig a little bit further into some of these upcoming readouts, just how should we think about setting expectations for POLARIS-1, 2 and GLORA-4? Then just turning to olverembatinib, you highlight some of your competitors on slide 17, but if you could just provide some further detail or perspective on what you see are the biggest differences for your molecule versus those competitor agents on both efficacy as well as safety. Thank you.

Really great question. First, based on the preclinical data, our drug is probably among all the TKIs or all LSD1 inhibitors, the most potent one against the T315I mutation and also the compound mutation. Because in the BCR-ABL gene, the mutation not just happen in one hotspot. The T315I is considered a gatekeeper mutation, differentiate those in terms of third-generation BCR-ABL inhibitor. On top of that, there is also the more than one mutation, called a compound mutation, in the same cell. Currently, asciminib and also those TERN-701 or ELVN-001 do not have those strong data. So olverembatinib is the most potent one and also most active one against a wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of layline CML patients.

Currently, even though asciminib has approved a label with only U.S. to treat the patient with the T315I mutation, they need a five-time dose, and also in U.S., that is 5x the cost, almost a million dollars. I think that in the layline CML, patients with mutations, we do show probably the most potent one. ELVN-001 or TERN-701 now with Merck do not have those data. They are also mostly in the early phase I or II. In the U.S., because the Project Optimus, we have those data four or five years ago with MD Anderson, that we have patient basically unmet medical need. Patient who fail both ponatinib and asciminib are the patient with no other treatment options.

Because of the Project Optimus, FDA do not allow the single agent, single arm period of phase II trials for the registration. That is why we have to conduct the RCT. We have to have the control arm like bosutinib. I think that none of those competitive products have those data or registration trial agreement with the FDA yet. In the real world, the consensus among the CML experts community is you want to give the best BCR-ABL inhibitor to the patient failed after first-line early. You do not want to wait until after four or five line. You want to give the strong one so the CML patient who achieve deeper response, like a MMR, MRD, an active CR, or the MR4 or DMR of 4.5.

Patient who can achieve a deeper response early would be able to achieve TFR, and in certain cases, maybe, drug-free for many years, defined as a clinical cure. I think that is important. That is why we have a second-line data. We have the real world data perspective comparative study to demonstrate that olverembatinib could be the choice of patient who failed the front line. It does not matter is it TKI or asciminib or any other allosteric inhibitor. That is the goal. That is the key differentiation we have been showing, presented with the clinical data.

Thank you. Appreciate it.

Thank you.

Your next question will come from the line of Gregory Renza with Truist Securities. Please unmute and ask your question.

Greg, good morning, and thank you, Ascentage team, for taking my question, and congrats on the progress. My question just to start is just on the lisaftoclax. Certainly, when it comes to the commercial trajectory over this year, can you just comment about how that is perhaps changed since sonrotoclax has entered the market? Are these two drugs competing directly, or is lisaftoclax certainly as approved in the post-BTK monotherapy setting, just producing more of a meaningfully different initial patient mix? Maybe just comment a bit on the five-day ramp-up as you have mentioned, how that is perhaps translating to more measurable real-world advantages in China. Thank you.

Great question. Overall, Bcl-2 is a very tough target, right? We have been working on that in the lab for 30 years, clinically for 21 years, advanced three products in the clinic, but only the venetoclax made to the market. Again, we always compare with venetoclax, and that daily dosing up was a key differentiation in the beginning. We are the only one approved to go to the clinical trial and approve the label with the clinical data. I think in the CLL patients, some of the early risk was in the tumor lysis syndrome. That is why venetoclax, and also sonrotoclax went to this weekly dosing up, right? Require hospitalization and close monitoring because of tumor lysis risk.

But on the other hand, because venetoclax is already on the market, same with sonrotoclax now, the differentiation in the chronic dosing patient, like a CLL, is actually the safety. If the drug tolerate well with less tumor lysis syndrome, less bone marrow toxicity primarily in our case is we have a shorter T1/2 that translate into better safety profile, less neutropenia, thrombocytopenia, and also much less infection. Some of the hematology malignant patients in the clinic presented first is actually the infection, like a high-risk MDS. And then they found out actually the bone marrow is the one has the cancer cells. So the patient with a high risk of infection is important you have lower risk of DDI drug to combine with.

Not just combine with azacitidine, standard care for high-risk MDS right now, but also in some case of marrow disease especially the multiple myeloma, the combination with antifungal drug is essential for those patients. I think the key differentiation, as we alluded to before, is less is more. So they compare even with sonrotoclax now on the market, you see from the label that they even have a higher risk of DDI than venetoclax. Okay? So I think that the differentiation in terms of daily dosing up convenings, better safety profile tolerance, and lower risk of DDI is important for these chronic dosing leukemia patients. I think that those are the ones we remain confident will show the benefit to the patients globally once they reach to the market.

That's really helpful. Thank you, Dr. Yang. Maybe just a question on the pipeline. You spoke highly of APG-115 and that development flexibility that you have with the program as well as APG-3288, and certainly the synergy potential there with your portfolio. Can you just comment about how you and the team are thinking about prioritizing your resources to accelerate the programs beyond the two commercial assets, and which ones you're perhaps most excited about? Thank you.

To be honest, it's hard to say which one. It's all data-driven. But to your question, we are very happy to see we demonstrate clinical benefit in the pediatric soft tissue tumor setting, combined with, in our case, a Bcl-2 inhibitor. So one of the challenges for the MDM2-p53 target, that's why currently no approved product yet, is this negative feedback loop and also the requirement of a combination. We have tried multiple, including the combo with KEYTRUDA in the phase II setting, multiple tumor indications, but we haven't really seen the signal for the registration path before. But currently, we do see now with this combination with the Bcl-2 inhibitor, clinical benefit and the MOA of synthetic lethality.

On the other hand, even those from the competitive product, the Kartos compound also entered the phase III registration trial with the add-on strategy of a JAK inhibitor in MF. Obviously, it is encouraging to see Ipsen enter the acquisition with potentially USD 1.75 billion. I think there is a potential, maybe at the end of the tunnel, to see that finally MDM2-p53 inhibitor may enter the market or a registration path. For your question, I think among the pipeline, we have five of them right now. Each one of them has a unique different strength differentiation based on the current data. Obviously, the two new ones, the EED inhibitor APG-5918. We will show the data at the ASH this year. We have completed close to 100 patient phase I trial in informal setting. We are very excited to show this data at the upcoming ASH, that is already submitted.

For the EED inhibitor, there is also potential in prostate cancer in some other settings of a solid tumor. I think there is a lot of potential in the EED. We are the first one in China, globally the second in oncology setting. I think there are a lot of potential in the EED in both Heme and solid tumor. Of course, the BTK degrader APG-3288 is also very exciting in terms of oncology, non-oncology. I think they currently, in addition to the two approved product in China, globally for registration trial, clearly the focus, right? We want to getting the first NDA filed with the FDA in those two product. As you can see on the five clinical stage asset, at least those three I mentioned clearly show the leading advantage globally with clearly clinical data.

I think those are still early, not reaching the registration trial yet. So I think we have sufficient resources in terms of budget and the clinical team to advance those trials. Again, which one is a favor is hard to say. It is all data-driven, but I think all these three do have a really exciting data and a path to registration.

Yeah, maybe just to add to that. As it relates to our presence in China, our legacy in China, we are one of the few companies that can de-risk and gain real information about how to tactically prioritize our portfolio and what to take and execute in other countries and globally. So I think that is important to keep in mind about us.

That's great. Thank you, gentlemen, for all the color, and congratulations again.

Your next question will come from the line of Mayank Mamtani with B. Riley Securities. Please go ahead with your question.

Yes, team. Thanks for taking our questions and appreciate the helpful detail. A couple of quick questions on lisaftoclax. I think you were talking about ven-resistant patients development being explored. Could you maybe just touch on how quickly you can generate data there? What does a patient pool look like? On GLORA-4, if you could maybe comment on your expectation for CR rate and TLS, and how maybe the interim OS analysis would be handled in the study if there's anything early built in there. Then I have a follow-up question on POLARIS.

The first question, I think maybe Yifan can answer.

Oh, great question. Yes, based on our preclinical data, we have reported using the lisaftoclax in combination with olverembatinib able to overcome venetoclax resistance, which we have previously reported at the AACR. We also use very preliminary data we submitted to this year ASH, and when the data mature, we have data demonstrated the combo able to overcome the venetoclax resistance. The data is preliminary, but very exciting. We submit the abstract to ASH. That's address your question. We in the process in globally, including in China or outside China in U.S., and we try our best effort try to enroll more venetoclax treatment failed patient population, using different strategy, based on the known resistant mechanism, to target this ven-resistant AML population, either using the combo or our other compound, APG-1252.

To address your question, GLORA-4 study, as we mentioned, because this is a double-blind randomized study, we cannot analyze the data early, because the enrollment's still ongoing. But as I mentioned earlier, we plan to complete the enrollment either by the end of this year or early next year. Because based on the current design and the dual primary endpoint, we're able to submit the NDA, and using the CR rate as the primary endpoint. Continue to mature the OS data sometimes next year.

Thank you. I appreciate the detail. On a similar kind of question on POLARIS-2, on the treatment effect for a 24-week MMR rate, if you could maybe just comment on what you've powered the study for. I was also curious because your MMR rates grow over time, 48-96 weeks. How are you handling crossover from control arm ponatinib there? Do they have option to get your drug, or they're moving on to other trials? What sort of longer term efficacy we can get there?

Very good question. Based on the current study design, at the beginning, FDA denied our study design to allow patient crossover from the control arm to the investigation arm. Later on, we tried again to request the FDA finally give the green light, allow those patients who failed from the control arm to crossover to olverembatinib. That will make the study more attractive, number one. Number two, regarding the endpoints. Currently, we use the 24 weeks, at the 24 weeks MMR rate as the primary endpoint. The basic study design is powered enough and double the MMR rate compared to the control arm.

Okay.

Also, just to add on one, the design of the POLARIS-2, because of the Project Optimus, you have to do the RCT, and you have to have a control arm. But in that particular setting, FDA did agree this is a 2:1 ratio, and also allow the crossover. Remember, the POLARIS-2 also has the arm B, the mutation with T315I mutation patient only that we can do the single arm design with the 48 patients. So I think the total POLARIS-2 is 333 patients and enrolled well, and then the six months MMR rate for the initial filing of the NDA with the FDA.

Awesome. Thank you. Last one for Veet, if I may just, if you could comment, Veet, on your OpEx trajectory and if you are getting to peak. I know you have a lot of registration studies. Just maybe comment on where we are with the R&D spend, on what you expect to see with the pipeline over the next 12 months. Thanks for taking the question.

Yeah. Great question, Mayank. So, as I said, we reaffirmed our cash runway and we are happy that we have been adhering to our forecasted spending given the scale of our studies, globally, multiple countries. We are at a point now, what we wanted to do for this year was to de-risk the balance sheet in 2025 so that we can execute on enrollment. This year is the year of execution. Enrollment is going well. Dr. Yang and Dr. Zhai would discuss that. So I think, as it relates to the expenses for the studies, given we are at the late stages of enrollment, we are now at the peak as it relates to OpEx spend. So, all that is going as planned and expected.

We are not only in a position to complete enrollment, but also with the cash we have on hand, but also for the data, as well as our multiple NDA filings. Those are the key expected milestones we have with the cash in our balance sheet.

Got it. Thank you, Veet.

Of course.

Your final question will come from the line of Michael King with Rodman & Renshaw, LLC. Please unmute and ask your question.

Thanks for taking the question. Congrats on the progress, guys. I wanted to drill down a little bit further on the balance sheet question. If you could talk a little further about capital allocation, because you guys do have a fairly hefty burn rate, and even with the Takeda opt-in, you are going to require a lot of capital. In highly competitive markets, even with differentiated products, you do have entrenched competition. I am just wondering if you feel any urgency to do additional partnerships or other types of arrangements where you could lay off some of the capital allocation demands.

Yeah. Maybe I can start. Or go ahead, Dr. Yang.

No, Veet, you go ahead.

Yeah. In terms of allocation of our total budget to programs, we have not given that level of attribution. But, as I stated, we have prioritized so that we can align our spend with expected major milestones and catalysts. Obviously that is what we wanted to establish. What we have done is with the dual listing, steps we have taken is allow ourselves, we believe, within as reasonable as possible, maximal flexibility and optionality in terms of various alternatives to raising capital. Obviously, when it comes to commercialization, that requires expansion capital and we believe as a company, we have allowed ourselves to hopefully deliver on catalysts, gain value, and thereby have less dilutive sources for raising capital going forward. Of course, with Faiçal on board, the optionality as it relates to potential partnerships when it makes sense as well.

We are not in a pressure for one particular path, which is exactly where we want to be at this point.

I think I fully agree. Just add one more point, that our current cash runway, as we stated before, consistently can support our R&D plans through the end of 2027. More importantly, with nine registration trial and four global clear by FDA and EMA, majority of this enrollment are already done. That's why you see the first six months, we have R&D expense of more than 30% increase, primarily due to this heavy enrollment. But the good news is that most part of the cost is already at least more than halfway done. Of course, we remain open, flexible for many options for the fundraising, and also partnership, other source of income. On top of our positive continued growth revenue with the two product sales in China. I think we're really unique.

It's not just because we have legacy and resources in China, but also steady growing revenue income from China and looking forward for the global commercialization and the revenue as well.

Well, thanks for taking the questions.

Thank you, Mike.

That concludes the question and answer portion of today's call. I will now hand the call back to management for closing remarks.

Thank you all for joining us. I think this interim report, again, position us well to be the global player in the Heme malignancies. More importantly, we are advanced well in terms of all the key registration trials with the target to complete them by the end of the year or early next year. More importantly, we are in the position. If you look at some other competitor or the really excellent biotech company this time last year. I told my team and many investors, Ascentage will be a different company by the time next year. We are looking forward to your support and looking forward to working with our team, investors and HCP globally, to make those novel, safe, efficacious drug into the global market to help patients with unmet medical need globally.

Thank you all for your attention and support.

Good day everyone, and welcome to Ascentage Pharma's 2025 annual results earnings call. At this time, all participants are in a listen-only mode. After management's prepared remarks, we will open the call for questions. As a reminder, today's call is being recorded. Thank you for joining us. I will now turn the call over to Yiyi Shen, Senior Director of Investor Relations, for the safe harbor statement. Yiyi, please go ahead.

Thank you, operator. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions. These statements involve risks and uncertainties, and actual results may differ materially. For a full discussion of these risks, please refer to our filings and disclosures. On today's call, I am joined by Dr. Dajun Yang, Chairman and CEO, who will provide an overview of recent developments and 2025 annual performance, as well as Dr. Veet Misra, CFO, who will go through the financial highlights. The presentation will then be followed by a Q&A session. During the Q&A session, the team will be joined by Dr. Yifan Zhai, Chief Medical Officer, Dr. Shaomeng Wang, Co-founder, Chief Science Advisor, Dr. Zhichao Si, Head of Commercial. I will now turn the call over to Dr. Yang.

Thank you. Good morning. I'm Dajun Yang, Chairman, CEO of the company. Today, I'm very happy to present our 2025 full-year financial results and the corporate update. I will have the following agenda: business update, R&D highlights, financial results, and the Q&A session. First, on the business update. 2025 was a breakout year for Ascentage. First, we have achieved excellent total revenue, over 90% of growth and $82.1 million. Our year-end cash balance is about $353.2 million, cash runway through 2027. I think that 2025, we are the first dual-listed biopharmaceutical company on Nasdaq, following our Hong Kong Stock Exchange listing 2019. We successfully raised approximately $322.6 million dollars through IPO and a follow-on offering. It's the first time we have a dual commercial product. Based on that, we established a fully functional, large-scale, and fast-growing commercial team. Currently close to 300 staff.

We are on the path to be a premium global commercial hematology oncology company. We also achieved many major R&D milestones. These are the following examples. First, the lisaftoclax approval as a global first single agent BCL-2 inhibitor after BTK treatment in CLL and SLL. GLORA-4 phase III registrational trial received clearance globally, including FDA, EMA and CDE. This is a truly unique opportunity as we are the global phase III registrational trial in high-risk MDS, the only one in that phase III registrational stage. POLARIS-1 for the Ph+ ALL. The phase III registration trial also received clearance globally, including FDA, EMA, and CDE. Part one data also reported at ASH, demonstrate strong 64% MRD negative CR rate in the first-line Ph+ ALL. Olverembatinib granted breakthrough designation for the first-line treatment of Ph+ ALL by CDE.

We are also really proud to have FDA and CDE IND clearance for our novel BTK degrader, APG-3288. Both lisaftoclax and olverembatinib entered 2025 CSCO guidance. Multiple oral presentations at ASCO and ASH 2025. We continue to lead in the global innovation for many of our products, including multiple presentations at ASH, AACR, ASCO, EHA, and other conferences. Also we publish many peer-reviewed top journals. I think that here is our summary of world-class innovative, highly de-risked, and super late-stage pipeline. Here are the list of seven novel compounds. The first two, olverembatinib as a novel third generation BCR-ABL1 inhibitor and lisaftoclax as the novel BCL-2 selective inhibitor. Both have been marketed in China. Also entered four global registration trials cleared by FDA/EMA. Total, we actually have nine registration trials for multiple indications.

We also have several novel, potentially first-in-class compound targeting, such as the FAK/ALK, ROS1 triple kinase, the MDM2/p53, the dual PI3K/Akt, and the PRC2 third generation EED inhibitor. More importantly, we have newly cleared phase I novel BTK degrader, APG-3288. All of these are running the trials in U.S. and China and in multiple countries. Many focus on hematology oncology, but also have potential and also in the clinical stage testing indications such as anemia. We have built a very large commercial scale in China with the dual product approved, especially for our PI3K/Akt inhibitor, the SOFIA class was ahead of our schedule last year. With the two commercial products, we have built over 270, by the year-end, commercial team. Covered 1,500 hospitals and more than 800 DTP pharmacies. Our dual engine strategy worked well.

As you can see, our last year commercial revenue, that's a transition for Ascentage from relying on the investment in medicines and also BD income to the last year, 100% sales of the commercial stage of product. That's a really important transition for a company to be able to self-sustained with our own revenue to support our own R&D program. If you look at just our olverembatinib alone, we have a strong sell following full NRDL listing covering CML with or without mutation. If you look at the total sale, which is $62.2 million, that represent 81% year-over-year growth. They will continue to cover more hospitals, DTP pharmacies, and also a broader reach to the tier 1 hospitals.

With the full NRDL coverage and also translating into very long DOT, that will support sustained growth as the patient continue to use our drug over a long time. If you look at the SOFIA class, first, this July approval was ahead of schedule, we built a very fast and full functional commercial team dedicated to the SOFIA class. The streamlined go-to-market strategy using the national commercial infrastructure really helped us to rapidly expand the sales force and our hospital coverage. Just the first five months, we have reached more than $10 million sales. This is among top, at least in the hematology oncology product sales in the first couple of months in China. Let's go to the R&D highlight. First, let's look at our SOFIA class. It's actively amending its global phase III registration trials.

Our approval as a single agent for CLL/SLL after BTK inhibitor is really represented the first label for the PI3K/Akt inhibitor. As you know, venetoclax was approved 2016 and continually, the only single agent was limited to the 17p deleted CLL and SLL. The other CLL/SLL is all combination with the CD20 antibodies. Our GLORA-2 and GLORA-3 also received FDA, EMA, and the CDE clearance. More importantly, I think that the GLORA-4 is the first-line high-risk MDS in combination with AZA or without azacitidine control arm. Both received the FDA, EMA, and the CDE clearance. We are continue pushing forward all these important global phase III registration trial. I want to share a few important clinical data with you. With the single-agent approval, based on the CC 201 registration study, those patients actually have much poor baseline characteristics.

The CDE actually gave us very high bar about four or five years ago, required all these CLL/SLL patients have to fail both BTK and CD20 antibody-based therapy. Many of them have a high risk of complex karyotype, and also many have multiple mutations. We achieved a very good efficacy as a single agent and demonstrate a favorable safety profile. If you look at another key data in the AML and the MDS, actually this is primarily U.S. and Australia data with the leading PI from the U.S., and this actually has presented both at the ASCO and the ASH. If you look at our ORR as a combination with the AZA, in the naïve, the newly diagnosed AML patient, we achieved the ORR 83%. More importantly, in some cases, about 22 patients who have failed venetoclax, we also achieved 32% ORR.

In the MDS, we have in the newly diagnosed, 80%, and in the second-line R MDS, we have 50% ORR. I think based on those excellent data and many other clinical data, FDA gives us clearance to conduct global phase III registration trial as a first-line for the high-risk MDS, and this has been cleared by FDA, EMA, and the CDE, actually, among close to 20 countries' regulatory agencies. We are actively enroll patients in U.S., Europe, China, and throughout the world. If successfully carry out, lisaftoclax can become the first BCL-2 inhibitor for the treatment of first-line high-risk MDS. This is really a global unmet medical need, as there's no targeted therapy approved in the last 20 years, and current therapy have much poor efficacy, and five-year survival rate for high-risk patients is only about 16%-24%.

We are also very proud these global efforts are leading by Dr. Guillermo Garcia-Manero from MD Anderson and Dr. Xiaojun Huang from Peking University People's Hospital, and many excellent expert and PIs for MDS around the world. Based on the public information, we want to highlight few key difference of our drug versus venetoclax or sonrotoclax. If you look at based on the same similar registration trial study, again, this is not a head-to-head comparison, but a really similar patient population, including those in China. If you look at the SAE instances, it's much higher for venetoclax or sonrotoclax, and the infection rate also significantly higher. That's consistent with the clinical observation that lisaftoclax have a better safety profile, better tolerance, and more importantly, we have a better drug compatibility. CLL/SLL patient often are elderly and immunocompromised with frequent infections.

Commonly used antifungal drugs are strong CYP3A4 inhibitors. Does not affect our lisaftoclax PK. If you look at the PK variability in combination with some strong CYP3A4 inhibitors, I think the impact for lisaftoclax is minimal. For other two drugs, either need to about eight times or 11 times need to be adjusted dose if they are combining those. That will strongly affect clinical combination studies. If you look at the P-gp or BCRP substrates or inhibitors, lisaftoclax is probably the one have a minimal risk in those combination studies. No need to adjust dose with many BTK inhibitors. I think those are really unique advantages for lisaftoclax as the BCL-2 selective inhibitor. I also want to highlight a few important progress made and summary here for olverembatinib. Olverembatinib is approved with full coverage by NRDL.

We see excellent commercial coverage and revenue growth last year. Globally, we are conducting POLARIS-2 for the CML. This single-agent study, RCT with the bosutinib as a control arm, also received the FDA, EMA, CD, and the PMDA clearance. We are actively pursuing advancing the global enrollment. POLARIS-1 is very important. This is the first time we got a clearance last year for the first-line Ph+ ALL. This also cleared by FDA, EMA, and the CD in China with a breakthrough designation. Part 1 of this trial, the same trial design data was presented at ASH. You can see the data from next couple slide. In the part A of the phase III registration trial, in combination with low-intensity chemo as a first-line, we have achieved 64% MRD negative CR rate.

This is almost double the same patient population for the ponatinib, which only have 34.4% MRD negative CR rate. This actually is among all the BCR-ABL inhibitors, the best one. We actually almost double the currently the best BCR-ABL inhibitor for the same patient population. Also demonstrate really well safety profile. Another data is looking the potential second-line treatment for the CML CP patients. This is also, again, presented at the ASH last year. We can achieve more than 50%, I mean, 70% CCyR rate, more than 40% MMR rate. Also have a really durable sustained response. Another important is in the blast crisis of the CML. I think we demonstrate in more than 64 patients with blast phase and also some serious cytogenetic abnormalities and complex karyotypes.

Those patients did very well. Also into the sustained remission with improved survival and a much reduced non-relapse mortalities. Another potential treatment is really for the combination with our olverembatinib. In this case, it is actually in the pediatric patient population that is a first-line regimen in the Ph+ ALL. Demonstrate very excellent efficacy and the safety profile. I think this would be really important for some of the patients to receive the chemo-free and the two orally active agent with a long-term benefit. Olverembatinib as a multiple kinase inhibitor also demonstrate clinical benefit for some rare hematological malignancies, such as this very hard to treat myeloid or lymphoid neoplasm with FGFR rearrangement. This actually take a while to recruit those patients, but most of them achieve the excellent response clinically. We continue to push our pipeline.

In the interest of time, we only show you one example as our novel BTK degrader, APG-3288. This actually we receive almost the same time clearance by FDA and the CDE. Based on the preclinical data, I think we also did a comparison with BeiGene or Nurix Therapeutics BTK degrader demonstrate good selectivity and potency. We'll push forward this compound in U.S. and China for multiple indications. I think that in summary, lisaftoclax as a very safe and potent BCL-2 selective inhibitor. Some refer BCL-2 inhibitor as a small molecule of TD1. That really means it has multiple indications and also opportunity for multiple combinations. I think more importantly, we are probably the, globally, the only company has not just the BCL-2 selective inhibitor, but also olverembatinib, representing the best third generation BCR-ABL inhibitor and the MDM2-p53 inhibitor, and also the novel new BTK protein degrader.

As you can see, each one of these is a single agent or in combination, have potential to treat multiple B-cell malignancies, among many hematological malignancies. Lastly, I think I will turn the financial result to our CFO, Veet. Veet-

Thank you, Dr. Yang.

Let's go to the slide number 28. The revenue.

Thank you, Dr. Yeah. Thank you so much. Yeah. 2025 was a successful year for us as we established our commercial strength with now two approved novel oncology products. In 2025, our total revenue was US $82.1 million, excluding payments from Takeda as a comparison to last year, which represents a year-over-year increase of 90% on a constant exchange rate basis. This high revenue growth rate was driven by our aforementioned dual engine commercialization strategy as articulated by Dr. Yang, and centered on olverembatinib and lisaftoclax. Turning to olverembatinib and lisaftoclax individually, olverembatinib sales of US $62.2 million represents a year-over-year growth of 81%. Sales of this product reflected first full year of NRDL inclusion, hospital and DTP market penetration, which drove increased volume uptake. Turning to lisaftoclax, which was approved in July 2025.

First five months sales of $10.1 million was attributed to our established commercial infrastructure that was built to scale ahead of approval and is anticipated to drive strong market penetration going forward. At the same time, we continue to adhere to a disciplined approach to efficiently manage and prioritize our operating expenses to support accelerated commercial activity as well as our ongoing clinical studies, including global registrational trials. As you can see, our year-over-year increase in R&D expense from US $130 million to $163 million year-over-year, which is tied to advancing ongoing global pivotal studies, represents a 20.1% growth rate to support trials ongoing that are expanding and moving forward. In addition, the increase in S&D expenses, sales and distribution in 2025 from US $27 million to $51 million, was primarily driven for sales force expansion ahead of commercial launch of lisaftoclax, which is an efficient use of capital.

As you can see, the increase in these two major line expense items compared to our revenue growth demonstrates our disciplined approach. Finally, in terms of our cash balance, our 2025 year-end cash balance of US $353.2 million, compared to US $172.8 million reported year-end 2024, is a result of product sales and two completed successful financings in 2025. Our January 2025 Nasdaq IPO, as well as our follow-on offering in July 2025 on the heels of lisaftoclax approval, raising combined proceeds of US $322.6 million. As a result, this allows us to maintain our estimate of cash runway through 2027, as we've stated before, which importantly funds us through multiple key registrational studies that are being conducted globally and execution of our overall commercialization strategy. Thank you. I'll now turn it back to you, Dr. Yang.

Thank you, Veet. I also want to present our clinical catalysts and the milestone for 2026. On the clinical development side, our major focus will be advanced enrollment for the GLORA and the GLORA-4 registrational trial, and also advanced enrollment for olverembatinib in terms of POLARIS-2 trial and also POLARIS-1 trial. As we mentioned earlier with our team, the key word for 2026 is really the enrollment, and enrollment. We'll do our best to achieve and complete enrollment and then be able to file NDA in 2027. We'll continue to push the degrader APG-3288 global phase I study in terms of safety, tolerability, PK, and potential efficacy data. Also advance our EED inhibitor APG-5918 in both oncology and anemia. Of course, we'll continue to push other active compounds in clinical study in the U.S. and China as well.

I think that the major in terms of milestone for the clinical development are those highlighted here. On the commercial front, we will continue drive the sales growth for olverembatinib and also the lisaftoclax to the tier 1 hospitals and more pharmacies. For lisaftoclax, we'll do our best for the benefit of patients, especially CLL/SLL, to gather to the NRDL coverage in China in 2026. The key driver for Ascentage to be a global player in hematology oncology is really driven by the two novel and potentially best-in-class compound, olverembatinib and lisaftoclax. We also have a dedicated hematology oncology sales force, not just based on the really rapid scale in China, but more importantly, our global strategy positioning and branding.

With our world-class clinical execution and a proven track record of translating the clinical development into the novel commercial product and advance our best-in-class potential therapeutics in global registration studies. With the dedication and the effort from all our team and also our collaborators and the PIs around the world, we're really moving our pipeline to addressing the global unmet medical need, making Ascentage to become the global leader in these therapeutic areas. Lastly, with the patient-centric innovation and global breakthrough therapies, and with currently seven, we call the seven magnificent, seven active compounds, small molecule drugs in active clinical trials addressing multiple hematology malignancies from the CML, ALL to CLL, AML, MDS, multiple myeloma, and potentially some of the lymphomas and anemias. Hopefully, with all your support, we can make 2026 another successful year for Ascentage.

Thank you all for your attention. Now we'll be happy to answer any questions you may have. Thank you.

Thank you. We will now begin the question and answer session. To ask a question, please press star then 11 on your telephone keypad. We will take our first question. The first question comes from the line of Brian Cheng from J.P. Morgan. Please go ahead. Your line is open.

Hey, guys. Thanks for taking our questions this morning. Brian Cheng and Veet Misra, good to chat with you. First, Dr. Yang, you talk about how this year is really about enrollments. Can you give us a bit more color on where you are in terms of enrollment for your registrational studies, especially the GLORA-4 study in MDS with lisaftoclax, and also the POLARIS-1 study in Ph+ ALL, and related to dose indication, how should we think about the next data milestones at the upcoming medical conferences later this year? Thanks.

Thank you, Brian. Really excellent question. Let me address in these two parts. First, for the GLORA-4 MDS, high-risk MDS. We are very happy to see this phase III registration trial protocol receive clearance by not just FDA, EMA, CDE, and also among close to 20 countries regulatory agency. This is the first-line treatment for the treatment-naive, newly diagnosed high-risk MDS. More importantly, this is now really the only phase III registration trial in the high-risk MDS globally. We are very happy to receive the support from the PIs around the world. They are very enthusiastic for this clinical trial to help patients globally with the MDS. With the POLARIS-1, this is the first-line Ph+ ALL. As you know, we also presented a part one of the same protocol data at ASH.

The three months MRD negative rate CR is 64%, almost double the ponatinib on the same patient population, about only 34%. Those two registration trials, both for the first-line treatment, which will actually much easier enroll than some of the late-line protocols. Of course, also have a huge potential market return. With those two first-line treatments, you can see MDS, we are the only front runner in the phase III registration trial globally. There is almost no competition there. The POLARIS-1 is first-line for the Ph+ ALL, also with excellent data, potentially the best in class for the Ph+ ALL patient population. The enrollment is doing well, even though both only initiated late last year.

We see so far the very excellent enrollment and very strong support from the healthcare providers around the world. The POLARIS-1 only requires three months MRD negative CR rate as a primary endpoint. Also, we have strong support from FDA and all the regulatory agencies to support the protocol of the GLORA-4. Overall, we will do our best to achieve complete enrollment. With the current timeline and the primary endpoint, we anticipate doing the best we can, to be able to release the top-line data or complete enrollment, and to be able to file NDA in 2027.

Got it. Maybe just one more. Just how do you think about the commercial growth opportunities for both olverembatinib and lisaftoclax franchise this year in China? Are there any specific drivers that you see today that your sales team is fully leaning on? Then perhaps we actually have a follow-up after this. Thank you.

Yeah, maybe for the commercial part, we can have our Head of Commercial, Zhichao Si, to address the part of your question first.

Yeah. Okay. Thank you for your question. If you look at the actual driver of growth in 2025 in China, I believe there are several key drivers. First of all, if you look at our olverembatinib, which really benefit from the broader reimbursement support affordability after NRDL inclusion, which Dr. Yang also mentioned, also very strong patient affordability improvement. Second, if we look at our annual reports, we continue to expand hospital and DTP pharmacy access, with more than 800 hospitals and DTP pharmacy, which significantly improved the accessibility by the year-end, which also included more than 355 hospitals with formulary access. Hospital listing is very important in China market. Third, I believe if you look at the lisaftoclax, which was approved in China since July, we got sales for five months.

Lisaftoclax really give us a second growth engine after launch, generating more than RMB 17 million in the first five months on market. Fourth, I think we scaled our commercial organization. Dr. Yang and Dr. Wei both mentioned we scaled up our commercial organization meaningfully. Our team actually almost tripled compared to 2025 compared to 2024. This commercialization team growing to more than 270 people and converting more than 1,500 hospitals nationwide. I believe that's the key drivers for last year's commercial growth. Thank you.

Great. Maybe just lastly, just want to touch on your BTK degrader here. Dr. Yang, can you first give us a better sense of how you see differentiation compared to other BTK degrader that's out there? As you think about your phase I study, what would be good to see from this initial phase I?

Brian, very good question. For the first maybe clinical part, I will have our Chief Medical Officer, Dr. Zhai, to address. Yifan, can you hear? If not, maybe let me try to answer your question. First, we have conduct very thorough, of course, is currently preclinical data, to compare our BTK degrader with Vone or Nurix. Based on this comparison, we selected our candidate compound moving into the phase I. Based on the preclinical data, at least we show better selectivity and also more potency. That's number one. Number two, I think that as the BTK is validated target, the BTK degrader can take care many of the BTK inhibitors, covalent, non-covalent, mutation or not, basically have a broad efficacy in the oncology space.

I think the most unique for Ascentage, once we go through the phase I typical safety tolerability PK and some signal of efficacy, with the potential RP2D, we probably move very quickly into the potential single agent indications for the fast to market approach. The second part, I think unique to Ascentage that we have a very excellent BCL-2 selective inhibitor. The combination of a BTK inhibitor or degrader and a BCL-2 inhibitor could really offer some the hard to treat patients benefit. In the case of the CLL/SLL, at least with the fixed duration, is really a potential, even some case, clinical cure. That means there's no progression after 5 years treatment-- I mean stop treatment. I think that will also offer additional benefit, especially for the young patient with the CLL/SLL.

In combination with the BCL-2, maybe also can treat some hard to treat like DLBCL. Thirdly, I think also this part of our moving forward strategy potential, the maximum return, is that there are also many non-oncology indications for the BTK degrader, like autoimmune diseases. With those three reasons, we are really looking forward to full speed to push this novel BTK degrader into the clinic development and many other potential combinations and indications.

Great. Well, thanks for the color, thanks for taking our questions.

Thank you.

Thank you. We will take our next question. Your next question comes from the line of Biren Amin from Piper Sandler. Please go ahead. Your line is open.

Yeah, hi. Thanks for taking my question. Maybe to start, for olverembatinib, what is your market share in China versus asciminib and ponatinib? In which CML patients are you seeing the most adoption? Then I guess, for second half 2025, sales grew by about 7% versus first half 2025. What can we expect for the growth rate for olverembatinib in 2026? Thank you.

Very good question. 2025 was the first year for the NRDL coverage, especially with or without mutation. The patient population compare our first approved indication with T315 mutation only, the patient population more than tripled. That's number one. The NRDL coverage for this chronic patient is really significant as they can, average nationwide, can reduce at least 70% the payment. In certain better economies, the countries, I mean, for province, the reduction payment can be reduced by 90%. That's really significant as these patients are taking the drug a long time, right? Really good long DOT. The NRDL coverage in China for the CML patient, we see a really important benefit. The patient population in China as other lay line treatment, like you mentioned, asciminib or ponatinib, both were only approved last year. Okay?

They don't have any establishment or the data from China. We also have, last three, four years, market use, even though for small dedicated mutation patient population. Overall, the physicians and the patients are really well-educated, positioned, once you get into the full NRDL coverage. For both asciminib and ponatinib, they were not under NRDL coverage. Okay? That also limits the use of those two drugs, only got approved a year ago. They're not really much sales affordability for those not NRDL covered, the asciminib or ponatinib in China. Moving forward for 2026, we see the benefit of NRDL will continue as the price is good for two years.

Even with just looking a little bit next year ahead of NRDL renewal, we're also very confident as the new policy from the NRDL is to maximize the support for the novel agent and also those unmet medical need. I think olverembatinib is one of the examples of falling into the category with strong support by the NRDL. We currently, another important indication, also very high prevalence disease, is the Ph+ ALL. In the real world, we do have many Ph+ ALL patients benefit by the olverembatinib. At the same time, because they're not officially into the NRDL coverage, currently in this patient population, we still want to finish our registration trial, be able to guide into the NRDL.

Moving forward, I think there's a continued expansion and growth of the revenue for olverembatinib in China, both the CML and the Ph+ ALL.

Thank you for that, Dr. Yang. Maybe just a follow-up. Clearly, there's a lot of focus on the CML treatment landscape, especially yesterday, Merck announced acquisition of Terns for RMB 6.7 billion. How do you think olverembatinib would fit into the emerging treatment landscape in the U.S. for CML? Second question, which of your global pivotal files across both olverembatinib and lisaftoclax can we expect to see data in 2027? Thank you.

Great. Really excellent question. Actually, we're all very excited to see the acquisition of the Terns by Merck, with obviously a really good price, RMB 6.7 billion in all cash. I think the positive side is really that means the CML market globally is actually quite big, right? To be honest, a couple of years ago when we were developing olverembatinib, there are some concerns from the investors that maybe this indication is small compared to lung cancer, breast cancer. If you look at the history, the first generation, the imatinib or Gleevec, actually just in the CML alone, the peak sale before patent expiration is almost RMB 5 billion peak sale annually, right? I think overall, the current CML market globally, the peak sale is about, I think the total annual sale is about RMB 7 billion. asciminib last year already reached more than RMB 1 billion sales.

I think that there's an estimate the potential, just CML global market, that ponatinib can reach over RMB 14 billion. I think that this is also supported by the Merck acquisition of Terns, primarily for the CML drug TERN-701. That's very great news, great stimulation for the market, for the investors confidence in this indication and novel drugs. To answer your question, I think we are very also happy we entered the option agreement with Takeda about two years ago, the June 2024. I think globally, Takeda will be our partner. I think as you know, in the CML and the ALL space globally, Takeda is really one of the leading company aside from Novartis. I think Takeda will be our strong, the best commercial partner for olverembatinib moving forward. The third part of your question is about the registration trial of the two drugs, right?

Yes, that's correct. Which of your trials could we expect to see data in 2027 that are global pivotal?

Yeah, I think we currently pushing forward very full speed for the best effort for the GLORA-4, the higher-risk MDS registration trial, and also both POLARIS-2 and POLARIS-1 for the olverembatinib. I think that the POLARIS-2 or POLARIS-1, POLARIS-2 is 6 months MMR rate after the last patient, for the potential accelerated approval, and POLARIS-1 is three months MRD negative CR rate. I think that once we complete enrollment, those two probably, most likely would have an opportunity to file the NDA in 2027. The GLORA-4 actually also have a good chance because we enroll patient very fast, as in this indication with the BCL-2 inhibitor. We are the only registration trial globally for higher-risk MDS because many drugs fail, including Verona trial was negative. We do see a very strong interest and a really good enrollment in that space.

With the current protocol achieved, I think this is, in my 20 years of drug development record, is really the first time for the registration trial of the same protocol approved, cleared by multiple regulatory agency in the same indication. As you know, in our CRO, we actually did three different registration trial, because the different landscape and the different regulatory requirement. I think we're very happy to see the GLORA-4 registration trial enrollment is actually really promising and with potentially also looking forward to have the NDA filing in 2027.

Perfect. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Gregory Renza from Truist Securities. Please go ahead. Your line is open.

Hi, Dr. Yang and Ascentage team. Congrats on the progress. This is support on for Greg. Continuing on the theme of the last question, was wondering if you could characterize olverembatinib's profile relative to TERN-701, particularly around the 24-week or six-month MMR rate with your existing data. As a follow-up, I know you have a POLARIS-2 study going, but curious about potentially expanding into second line, earlier lines in CML. What's the progress on that one? Thank you.

Thank you. Very good question. Obviously, we're very happy to see Terns' acquisition and also Eleven data presented at the ASH last year. I think olverembatinib will really have a unique advantage based on the clinical data, right? We probably the same ATP binding inhibitor as Eleven, and Terns is more like asciminib as allosteric inhibitor. Do remember, both drugs are in phase I or phase I/II, but they have much less patient number compared to olverembatinib. This is based on current data, they are less than 100. Also the dose, in terms of for the RP2D or registration trial, has not established for both drugs.

This is based on the current published data, it's not clear they're working on any, the gatekeeper mutation T315I or those with compound mutations, is not reported or based on the assessment data, it require five times dose for those with T315I mutation. Clearly there's no long-term safety data or efficacy data and there's no also report on any efficacy in the Ph+ ALL. Specifically, if you look at the, you mentioned like MMR rate, I think one is much less patient number. More importantly, if you look at the line of prior treatment, we published the data on JAMA Oncology a year ago and also have the presentation at ASCO and ASH, that the patient population we treated in U.S. primarily with the PI, MDS and others, were heavily pretreated.

They are representing the CML patient of fourth or fifth line, and one third of them has a T315I mutation. I think that you know all the BCR-ABL inhibitor, either kinase inhibitor or allosteric inhibitor, the response is really dependent on the patient baseline characteristics and how many prior lines treatment and mutation profile. I think that of course, this is not head-to-head comparison, just with current data, I think that we really demonstrate very broad, very potent activities and also long-term safety profile and efficacy as well. Another thing I think for both drugs, especially under the Project Optimus, FDA would require Terns' compound or the others have to do the RCT, right? They have to do the RCT trial to get approval. In that case, they also must have a control arm.

It's hard to see what would be the control arm, but these are definitely required based on the Project Optimus. The Optimus dose in terms of safety, efficacy and the RCT design and the control arm. I think overall we are really confident, especially with our partner, Takeda, we're going to position well for the early-line CML, for those with mutation and also very active action the data in the Ph+ ALL. We already conducted, published the ASH data for the second-line CML patients. I think actually in China, the approval label is what we call the near second-line approval because it says 2 TKI resistant and or intolerant. I think we are very confident we will benefit the patient, for those early-line as well.

Of course, we'll conduct more studies, especially after we complete the registration trial for olverembatinib.

Got it. If I may squeeze in one more. Lisa has really strong start following 5 months of launch. We know that ViiV has their BCL-2 inhibitor just approved recently as well. Just curious how that would play into dynamics for Lisa's uptake in 2026. Thank you so much.

I think that in China, we were the first domestic BCL-2 inhibitor commercialized last year. We were at least 6 months ahead of ViiV's Sarepta class approval in China. That's number 1. Number 2, I think based on the current data, safety, and also another thing is the Sarepta class dosering-up, is similar to another class, weekly dosering-up. The starting dose for Sarepta class is actually 1 milligram. The approval dose is 320 milligram. From 1 milligram to 320 milligram, and with the 5 different dose strengths and taken 9 steps, okay, to do the dosering-up. I think that's very not convenient for patients with CLL and SLL.

If you look at the overall safety profile of the SAE, even some of the deaths in that registration trial and the infection rate and so on, this other class is probably the best among the currently three market BCL-2 inhibitor. Actually, based on the published drug label, certain class actually have even worse DDI risk among the three drugs. I think that we are confident that we will continue to do well and expand commercial sales coverage and also especially the registration trial among the globally for the MDS. Also, our GLORA-2 and the GLORA-3 are also approved by CDE and other countries. The GLORA-2 will offer the patients with CLL the first-line treatment in combination with a color in a fixed duration. The 18-month fixed duration with the CIT as a control arm. I think that actually It's doing well in terms of enrollment.

The GLORA-3 is the AML, and we are also the first, the only, the AML registration trial approved by the CDE more than a year ago, and currently actively enrolling. This is the same validated indication, validated protocol. We expect we will do well for both GLORA-2 and GLORA-3 in China and a few other countries. Of course, they both are not yet for the U.S. or Europe because of the control arm or because of the trial design. I think to answer your question, I think we will do well, not just because we are 6 months ahead approval for Cerdelaclas, but based on the very excellent drug properties and the clinical data as well as the multiple indications, we are more in advanced position than Cerdelaclas in China or globally.

Thank you. We will take our next question. Your next question comes from the line of Justin Zelin from BTIG. Please go ahead. Your line is open.

Great. Thanks for taking our question. 2 questions from us. In terms of the China opportunity and your ongoing launch there, is there a target number of hospitals that you aim to have under formulary for both products that are there? Just trying to get some visibility into the long-term opportunity and peak sales potential for both drugs. The second question, coming back to your BTK degrader, certainly focus on the oncology side of things, but do you have any plans or intentions to go into non-oncology opportunities such as autoimmune or CNS diseases? Thank you.

For your first question, I think the hematology-oncology commercialization in China is really unique, because in China, those disease and treatment are highly concentrated to some of the top hospitals or cancer centers. To cover, our aim is to cover at least 80% of the sales potential. That represents probably around 2,000 hospitals. We already covered about 1,500 hospitals. The commercial team for the hematology-oncology is really different than like a solid tumor, lung cancer, breast cancer, as those indications probably you need easily probably 2,000 to 3,000 sales force to cover the 80% potential sales. That's the benefit to develop the hematology-oncology product in terms of commercialization in China. I think we currently have 300 staff in the commercial team. We'll continue to expand that to about probably 400 to 500.

With a much deeper coverage, probably close to about 2,000 hospitals. The second question I think is very interesting. As I mentioned, one of the reasons we felt that BTK degrader, even though we are not the first one, but it's not really too late. First is there's a lot of— I mean, this is validated target and also the BTK degrader to take care of many of the inhibitors, but it doesn't matter if it's a covalent or non-covalent mutation or not. That's one. Second is, as your question pointed out, the BTK degrader, like some of the other BTK inhibitors that actually have more probably potential in non-oncology, some of the autoimmune diseases, and also with just probably a little bit CNS penetration, which we have based on the preclinical data, those may actually to treat some of the CNS indications as well.

We do have a strong confidence and see much huge potential for the BTK degrader in oncology and non-oncology, and also with our BCL-2 inhibitor in terms of combination.

Thank you. Your next question comes from the line of Matthew Biegler from OpCo. Please go ahead. Your line is open.

Hey, great. Thanks, Dr. Yang for the question. Just wanted to piggyback on some earlier comments on the BTK degrader, particularly the ability to combine with Lisa in earlier line settings. I guess, like the 30,000-foot view question here is, do you think the CLL market is heading in the direction of an all-oral time-limited therapy, à la CLL17 trial that we saw at Ash? Do you think that that set up or how do you think that set up plays to Ascentage's favor here with BTK degrader and with ? Thanks very much.

Excellent question. I think obviously the BTK inhibitor is well established for the CLL/SLL globally. The current inhibitor already generate annual sales more than $14 billion. That's a huge benefit. At the same time, as you pointed out, the CLL, especially some young patients with the CLL, they don't like to take either BTK or BCL-2 inhibitor for the lifetime, right? The fixed duration, especially the combination of the BTK, currently mostly inhibitors with the BCL-2 inhibitor, really offer the patients another option. They don't have to take the drug a lifetime, right? The current data pointed out actually, at least the combination of BTK inhibitors, primarily with the inhibitor, offer a good benefit in terms of really durable PFS over five years, right?

The BCL-2, our drug, the lisaftoclax, has a very unique benefit in terms of other inhibitors, is that we don't have a DDI issue. We don't have a DDI issue with the BTK inhibitor, and much less DDI risk with other potential antifungal drugs. That's very important. On top of that, with the degrader, it's not too late because they take care of any of the inhibitors' issues, mutation or not. I think our plan, and hopefully we can demonstrate that with the clinical data, is that the BTK degrader combined with lisaftoclax first, is to offer the fixed duration and be able to have long-term benefit in terms of PFS, and then In certain cases, because you offer the best treatment regimen early on, you may actually offer the clinical cure for some of the CLL patients. That's in the CLL/SLL space.

Number two, from the BTK degrader, I think another potential, especially in combination with the BTK inhibitor, may offer some hard-to-treat disease like DLBCL or in the case of BTK single agent failed patients, right? One of our strategies globally is our GLORA trial add-on strategy. The single agent alone of BTK inhibitor or degrader probably at least half of them cannot achieve the optimal response in terms of CLL. In that case, you combine with the BCL-2 inhibitor then offer the patients better response, deeper response, and potentially, in terms of fixed duration, to stop the treatment with the long PFS. I think that Ascentage is really in a unique position to have both the BTK degrader and the BCL-2 inhibitor for those multiple indications.

Appreciate it.

Thank you.

Thank you. We will take our next question. Your next question comes from the line of Christopher Liu from Lucid Capital Markets. Please go ahead. Your line is open.

Thanks for the question and congrats on the quarter. Just wondering if you have any insight into what the go, no-go decision would be from Takeda in order to opt in from their agreement.

First, our current partner agreement is for the option agreement, right? They have a competitive product, ponatinib, that is based on some antitrust rules. There are cases before that in the antitrust issue that they may have to return the drug if there is that competition, the antitrust issue. The current agreement but still is exclusive global partnership. Basically, both Takeda and Ascentage are bound to have that partnership to work together. That is number one. Of course, they have to get either clear antitrust or to weigh the patent expiration of ponatinib, which I believe is later this year or early next year. With that patent expiration, there is no issue in terms of antitrust issue. Thirdly, for your question, of course, first of all, we are already a partner. We are strongly bound exclusive.

At the same time, in terms of when to exercise the option, which I honestly cannot speak for my partner. With the Merck acquisition of Terns for over $6 billion, I think that there is no reason that we do not work together, and maybe work together early, in terms of exercising the option as your question. So I do think that it is a benefit to both parties that we move forward, pushing forward full speed on the olverembatinib commercialization for the global market.

For lisaftoclax, would you be looking to partner that asset as well, or are you pretty adamant about going alone with that asset?

I think we are really open and flexible. As I mentioned at the J.P. Morgan conference, we are open, flexible, we are ready to enter any partnership that will benefit, bring the synergy with our product and also the complementary resources to commercialization on the large scale on a more global market. Of course, at the same time, we are within the timeframe of be ready commercialization in two years. Many of the experts in the commercialization is that you need to be minimally ready two years ahead of your anticipated commercialization. I think that we are in a position and actively looking for the chief commercial officer. That is more, I would say, our dual strategy that combines business development, partnership, and also to build, at least in U.S., our commercialization capabilities. They are not exclusive. They really work hand in hand in parallel.

I think that either case will benefit strongly our lisaftoclax commercialization, at least in the U.S., and also through the potential partners, either U.S. or global. I think that we are in a really good position in terms of clinical development, be ready for commercialization, and also looking for the partners that can bring the best value to this product and also patients globally.

Got it. Thank you very much.

Thank you.

Thank you. We will take our next question. Your next question comes from the line of Michael King from Rodman & Renshaw. Please go ahead. Your line is open.

Thanks for taking the question. I had a question about the allosteric inhibitors. That was answered earlier in the call.

What's the question?

I was just looking for your commentary on the market dynamics of the introduction of some of the asciminib and the allosteric inhibitors in the CML space.

Okay. I think that the current data, first, asciminib as allosteric, is doing well, right? Last year it sells more than RMB 1 billion. In certain countries, like U.S., also received the conditional approval, I mean, accelerated approval for the first line CML. The Terns compound Eleven do not have data, at least clinical data, to show the activity in terms of T315I mutation, the gatekeeper mutation, and those with T315I mutation plus other mutations, the compound mutations. I think that they, I mean, ponatinib level, of course, there's a pattern and safety issues. Currently our strong competitor, to be honest, that we consider is asciminib. They're not active in about 40% of the lay line CML, which require five times dose or five times the cost.

All the drugs, based on current data, does not show activity or strong activity as olverembatinib in Ph+ ALL. I think that those two are based on the current clinical data, which olverembatinib has advantage over those asciminib. TERN-701 still early, require RCT trial approval by the FDA. More importantly, I think that the early lines, we are definitely the best and the most potent one, and the broad activity against all mutations. The early line, I think we are doing the second line trial. We do have data, early data to support that. I think that they focus. If you look at the current market this year, two of the second line actually is taking the most of the market shares. Among the $7 billion annual sales, two of the second line has been consistently taken each about $2 billion annual sales.

Okay. Moving forward, I think that currently there's, including the asciminib, there are five drugs with the first line label. For Terns or any other compound, trying to move into the first line is going to be heavy uphill battle. They also take a long time, and they're very costly. I think our focus is really moving forward and also based on the data, is probably olverembatinib would be the first choice of the TKI for the second-line patient. So in that regard, we don't worry about the competition of the first line. Actually, more first-line treatment, the patient will funnel through to olverembatinib in terms of the best second-line treatment.

Thanks for taking the question.

Thank you.

Thank you. There are no further questions at this time. I would like to turn the call back to management for any closing remarks.

First, thank you all for attending and also really excellent, insightful questions. This is a great timing in terms of our annual report for 2025, representing the first year we have a dual engine for commercialization, build a full-scale functional sales force, and also the first time as a dual, primary listed company on Nasdaq. Moving forward, we also see really strong confidence and broad potential in CML, ALL, and also really the probably cornerstone product for hematology oncology with our selective BCL-2 inhibitor. We are probably in a really fast position in the global novel product development that not just being the first approval commercialized in China in those products and indications, but globally, we are potentially best in class with the clinical data in terms of safety, efficacy, and also in the registration trial. I think that's a really unique position.

At the same time, of course, there's a huge potential in terms of commercialization readiness in U.S., and also looking forward to the partners for the global market and expansion. We are really excited with our strong achievement, the milestones, transformation year for 2025. Looking forward, we are more excited to see all the registration trial advance well, looking forward to be ready to have the commercialized in U.S., being the global leader in those therapeutic areas with best-in-class potential drugs for multiple hematology malignancies. Looking forward to working with you all and all the investigators and the investors around the world to bring the best drug to benefit patients globally. Thank you all. Have a good day. Thank you.

This concludes today's conference call. Thank you for participating, and you may now disconnect.