Ascentage Pharma Group Inter Aktie

Hello, and welcome to the 2026 Interim Financial results. [Operator Instructions] Also, as a reminder, this conference is being recorded. [Operator Instructions]

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 a 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 6 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 9 global registrational trials, 4 of which are cleared by both the FDA and 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 appointment of Dr. Faiçal as Chief Business Officer; and Mr. Jim Ziegler as Chief Commercial Officer. Both are with us today, I will be sharing preliminary thoughts.

So let's look at the next slide. So this slide, we have two approved products and the late-stage pipeline that's highly derisked. Olverembatinib, our third-generation BIO inhibitor have been approved, CMLCP in China since 2021. Tens of thousand patients have been treated today. The loss of patients on our drug have been near almost 10 years now. We have real-world long-term safety and efficacy data that really few companies and our stage can point to. We also have global registration trials, including FDA and EMA Clear that's ongoing. Our plan is to commercialize olverembatinib in the United States 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 to 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 have a unique daily dosing. We are the only one approved with that label, enhanced asset safety and as well as drug-drug interaction observed today is much reduced compared to other DL2 inhibitors. It also has FDA and EMA cleared global registration trials, GLORA and GLORA-4.

Behind those two, we also have 5 additional clinical stage assets or conducting trials in U.S. and China and the rest of world. APG-2449 is a triple kinase inhibitor covering FAK of ROS1 and MDM2-p53 inhibitor, APG15 and also targeting both TCR2 and XL APG1252 and EED inhibitor 591A and also the new 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 in the 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 experiences 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 attracts them to Ascentage. Faiçal, let me turn it over to you.

Thank you, Dr. Yang. My name is Faical Miyara. I'm the current Global Chief Business Officer at Ascentage. I have 20 years plus in oncology business development, search and evaluation and also involved in venture investing across leading pharmaceutical industry. I was in, as you see, involved in multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen as well as midsized biotech like Cadman and IO Biotech. I was also instrumental in the deal or the M&A that happened between Cadman and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executed teams at IO Biotech and Ipsen. And when I was at Eli Lilly, I advanced Erbitlar and Cyramza as a lead oncology products or antibodies and co-initiated the Pfizer Center of Therapeutic Innovation. So I'm very, very pleased to join this very, very good team at Ascentage, and we'll talk about our pipeline. It's very, very outstanding.

And with that, I'll leave it to Jim to give you some information on the Chief Commercial Officer.

Thank you, Faical, and good morning, everyone. I am also very pleased to join the Ascentage team. I've 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 United States and other key markets. I look forward to providing updates on our progress over time.

I'll now turn the call back to Dajun

Thank you, both. Let's look at our R&D highlights. Our development strategy is the engine for full global commercialization strategy, two approved hematology assets anchored 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 systemic therapy, including BTK inhibitors. Actually, we conduct the registration trial for the patients who have failed BTK inhibitors. So for that indication, we are actually global first one. But more importantly, we are running 4 global registration trials, 2 of them cleared by FDA and EMA, which each of them will have a transformative therapy globally. I think the most important one among the 4 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 versus two other currently on the market Bcl-2 inhibitors. As you can see, lisaftoclax was the only one designed with daily dosing up in the beginning and only one approved with only 3 dose strengths and 5 daily dosing up planned and then reach the dose of -- target dose of 600 milligram and continue. As you can see, the venetoclax was the first approved about 10 years ago, has a 5-week dose run up. The other one just approved venetoclax early this year with a 5-week dosing, I mean, the weekly dose up by the line dose cohorts, okay, because venetoclax start with 1 milligram. Initially in the trials was 9 weeks. I think they combined two into 1 week. So each week, they have do the run up of 2 times and then total 9 dose levels to reach a target dose. I think that's really important for the patients with CLL/SLL, the convenience and also reduce the time of hospitalization.

Let's also look at the summary of favorable safety profiles and better drug combinability. We try to compare in the same setting, the 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 3. If we look at the [ AAE ] instance, lisaftoclax is also much lower and no drug-related deaths reported today. And in the TK variability, I think the other two are strong, the only 3 or 4 inhibitors, and we show minimal fluctuation in plasma penetration compared to the other two. I think the -- also the low dose adjustment required compared to the other two in terms of DDI issue. I think for the chronic dosing patients like many hematologic malignancies, safety and tolerance and drug-drug interaction risk are important differentiation.

Let's also look at the key data in the U.S. trials, okay? In the MDS, lisaftoclax with azacitidine in frontline produced overall response rate 80% and 50% in relapse are MDS patients. And more importantly, we have a 40% CR rate, okay? And the time to response also really 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 a CR after two cycles with 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's also look at the AML case. The overall CR/CR 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 are actually with patients in U.S. and Australia. This is not the data -- clinical data from China. As we previously indicated, in the case of patients who failed venetoclax, which is truly unmet medical need globally, we still see a 31.8% overall response rate, with no cases of tumor lysis syndrome, same target, same pathway and the lisaftoclax remains active. I think that this -- based on the current clinical data of the resistance to Bcl-2 inhibitor, majority are not due to new mutations, but MCR1 upregulation and some also with Bcl-xL upregulation. So I think that explains 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 represents 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. And in our case, combination with olverembatinib would overcome venetoclax resistance in AML.

Turning to the second pillar of our product strategy, olverembatinib. I also want to highlight why we believe this can be a best-in-class third-generation BIO inhibitor to patients with CML in the second line or late settings. This has already been approved and highly derisked asset with several years of clinical and real-world use in China. We received validation from Takeda as they hold exclusive option to license olverembatinib outside Greater China and certain other territories. This was entered with Takeda about 2 years ago. Globally, the most important study for the CML is POLARIS-2. Part A enrolled chronic phase who has achieved -- who has received at least two prior TKI randomized olverembatinib against bosutinib. This is cleared by FDA and EMA. And there's also Part B, which evaluate olverembatinib in patients with T315I mutation. As you know, bosutinib doesn't have activity. So that's the single-arm trial. Overall, 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 strong activity in PH-positive AL. So POLARIS-1 is also important. This is our global Phase III study in newly diagnosed PH-positive AL, again, both cleared by FDA, EMA and CD 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's look at some of the important bridging study led by Dr. Ali Jabu at MD Anderson. This actually was conducted 4, 5 years ago. And Dr. Ali Jabu, as you know, is a leading investigator in CML and also PS-positive AL. In this particular study, we enrolled 62 heavily pretreated CML CP patients. More than half have achieved at least -- have received at least 4 prior TKI. They are like fourth or fifth line and half of them have received ponatinib and 1/3 of them have T15 mutation. I think with this really poor baseline patient population, we achieved MMR as a single agent, [ 42.9% ] in ponatinib-resistant patients, 33% in asciminib-resistant patients. And more importantly, 27% in patients who fail both ponatinib, asciminib. Basically, those are the patients with any -- with no other options, but single agent olverembatinib have pretty good efficacy. I think this treatment, again, strength the overall differentiation and the clinical efficacy versus ponatinib and asciminib. And also, we have a pretty long-term safety profile. In China, the longest patients have been using olverembatinib almost 10 years since October 2016. And in this particular patient trial, the longest patient treated in the U.S. is over 3 years with a manageable safety profile.

Let's 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 last -- in this year reported in a prospective control data in the second line and late-line setting, showing a clear benefit from switching to olverembatinib, type of evidence that remains uncommon in this patient population. I think the differentiation you can see is really dramatic, right? So if they don't switch to the best-in-class potential olverembatinib, the MMR rate remain only 10%. I think that's a huge benefit in terms of -- for the patients in the late line CML. Those patients actually have been treated with at least 2 TKI. Some of those also with asciminib. Olverembatinib delivered 6-month MMR rate, 54% and then even higher at 57% in 12 months. Those who didn't 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 and also important safety profile in terms of AEs.

That's also -- turning to Slide 17. I think that the benchmark is important because the [ NAND ] market changed over the last 2 years. I think in addition to the -- at least 2 years ago, the only competitive product we consider is the asciminib, but now there is two drugs [indiscernible] 701 and 1101 in the study in the U.S., okay? But first, I think the most important one, we are the only one have long-term evidence that other program doesn't yet have those are still in the Phase I or early Phase II, and we have 6 years follow-up for patients who are in the second line and 10 years for the first line of the Phase I trial. And we also have -- we are the only ones to have controlled comparative data set, okay? Those are new requirements from FDA in terms of product [ Optimus. ] So you have to run the RCT trial in order to getting the NDA approved.

Another important differentiation in the CML patient population is really the baseline, right? So you can see the patients treated with olverembatinib are more late line, heavily pretreated and also with mutations. I think that -- those data clearly demonstrated olverembatinib as the potential -- the drug of choice in the second line of CML of the patients who fail the most advanced available TKI. And I think I will show you a few more studies in the control -- in more details on the next slide.

Slide 18 is a real-world analysis of 69 blast crisis CML patients who went on transplant and 26 was treated with olverembatinib and 43 with the first- and 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, 1-year overall survival of 89% versus 71% and 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 and hard-to-treat CML patients.

Let's also take a look at the combination strategy. In the patient -- in POLARIS-1 with low-intensity chemotherapy in frontline. I think the POLARIS-1 three key important differentiation, the data. One, this is frontline newly diagnosed P-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 conducted Part A with the low-intensity chemo. As you can see, this demonstrates MRD-negative CR rate about 33%. This is almost double the ponatinib in the same patient population, the PON trial, about 34%. Of course, in the real -- in the trial data, the imatinib only 17%, dasatinib is only about 20-plus percent. 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 ASCO by Dr. Ali Jabu from MD Anderson, demonstrate that if combined with [indiscernible], we can achieve 80% MRD negative rate and 91% CR/CRi. We also demonstrate importantly, in the pediatric RRPH-pL patients, actually, those data have been available reported first time two years ago. We continue to see benefit of safety and overall response. I think very impressively, we achieved 89% overall response rate after cycle 2, day 15 and all complete response in an oral chemo-free regimen. I think this combination data is key because this is two orally active agent chemo-free in the pediatric ALL setting.

Moving on to the APG-15, another asset in our portfolio, small molecule targeting MDM2 P53. It actually holds 6 FDA ODD and 2 rare pediatric disease designation. This actually has been conducted, I mean, in our portfolio for a while as there's no approved product yet globally targeting the MDM2 P3 as P3 is one of the most important tumor suppression. But I think that you do see some recent progress that Ipsen achieved acquired [indiscernible] MDM2 inhibitor and with actually pretty decent $450 million upfront and up to $1.75 billion, including milestones for our Phase III program in myelofibrosis. I think that there is probably potential for the MDM2 P3 inhibitor combined with the JAK inhibitor in that actually trial as an add-on strategy. I think that data is encouraging. We also currently do that trial with MF patients. So again, this remains wholly owned by us. And in the ASCO, we presented encouraging data for APG-15 in combination with [indiscernible] class in the pediatric soft tissue sarcoma patients. Globally, pediatric rhabdomyosarcoma and other soft tissue sarcomas are truly unmet medical need. In that setting, we demonstrate good combination safety and impressive 23.5% response rate and also 70% disease control rate. I think those are encouraging data in the clinic demonstrate the orally active agent from Ascentage.

I think in the interest of time, I try to focus on mostly the key data. And here's a slide to show you that the cornerstone asset of Bcl-2 inhibitor DSO class combinability with three other targeted small agents are already active. I think we all know, as I mentioned, that the major -- the main reason for Bcl-2 resistance is the up regulation of MCL1. So we have demonstrated olverembatinib actually can indirectly down regulate MCL1. 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 positive ALL, but the patients with AML or MDS and the PH-negative AL, especially for those patients who failed venetoclax in the AML, and we have clinical data to demonstrate that in addition to what we showed before in the PH-positive ALL. And again, with MDM2, PP3 inhibitor, APT15, now we have clinical data to demonstrate the safety efficacy, especially in those hard-to-treat soft tissue sarcoma patients. And we are also moving into the DLBCL, AML and MD. 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 don't 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 BTK inhibitors. I think we can stay tuned for the progress for both oncology and the non-oncology indications with the BTK degrader.

I think that's all the highlight of our R&D. And let me turn the call over to our CFO, Dr. Veet Misra, and for the review of our financial results. Veet?

Great. Thank you, Dr. Yang, and 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 continue to expand our commercial reach and invest behind both products while maintaining a disciplined approach to managing operating expenses 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 the -- our expenditure and 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, and 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're pleased to report cash balances were $279.4 million as of June 30, 2026, as well as reaffirming our cash guidance runway through 2027, as we've said before. This funds us through multiple key registrational studies ongoing globally. And to emphasize, we are funding 9 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. And with that, I'll turn back the call to Dajun for his closing remarks. Dr. Yang?

Great. Thank you, Veet. So I think with the overall R&D highlights and the financial update, as you can see our last slide to show we have 7 active products in the clinic with 2 of them already landed approved in China. And -- but more importantly, with this already active target agent, we cover all majority of heme malignancies from the CLL to the CML, AML, MDS and also with clinical activities in potentially multiple myeloma and 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 and 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. And thank you all for joining us and also our team. And then I think now we are open for the Q&A.

[Operator Instructions] Our first question will come from the line of Brian Cheng with JPMorgan.

Faical and James, 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 update related to the NRDL listing? And then we have a couple of follow-ups.

Thank you, Brian. Very good question. So lisaftoclax was approved in China July last year. We are the first domestic Bcl-2 inhibitor approved in China. And also, we are the only one, the first one approved in terms of post BDK RR CLL/SLL patients in the registration trial. That was a tough trial, but we demonstrated good safety efficacy. And we clearly show the differentiation versus venetoclax or lisaftoclax in terms of the only approved daily do with a clear safety profile and lower risk of DDI. I think if you're looking not just the clinical data, but the NRDL reimbursement, less hospitalization and less risk and also convenience are important favorable factors for the NRDL consideration. I think currently, as an update, we have passed the initial review. We are on the final product list for the NRDL expert review right now. This year, the time line is actually a little bit ahead of previous time line. Currently, the -- both -- there are two groups, NRDL experts, officials and those health economics experts are conducting the meetings, reviews right now. So we may go up to a meeting with 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 probably only -- the concern we have or worry is working with the expert is the final price. But of course, venetoclax is already covered for different indications, AML in China is probably a benchmark. And -- but I think we are confident we'll have coverage for this indication, which is important in China, the NRDL is not just reimbursement, but the ticket to enter the hospital. Majority of hospitals in China rely on the NRDL approval to enter the hospital in terms of prescription. And in case of CILSL, this is chronic dosing patients, reimbursement by NRDL means they can reduce their out-of-pocket payment for the average 2/3, 60%, 70%. In certain regions, the NRDL coverage can up to 90%. I think that's 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's 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?

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

Sorry, Brian. So regarding growth study, sorry, I address somebody else's question. So could you please repeat the question problem.

Yes. I was just curious how the enrollment is going in the global studies like POLARIS-1 and also the GLORA study for lisaftoclax. How is enrollment going? And do you have a better sense of how -- when we're going to get the final data cut to file for the NDA?

So regarding all those global registrational trial, the team worked very hard and try to complete the enrollment as soon as possible. So it's still under the plan. in particular, the GLORA-4 study perhaps is under the radar and everybody pay a particular attention to that global registrational trial. Regarding GLORA-2, GLORA-3, actually already announced yesterday will already complete the enrollment. For GLORA-2 waiting for the data mature, GLORA-3 also very close and the remaining, we plan to complete the enrollment either by the end of this year or the early next year.

Maybe let me add a few points to what Yifan said. So we have said yesterday in the Hong Kong call that we complete enrollment for the GLORA-2, which is a frontline CLL setting combination with azacitidine and with fixed duration. And of course, that one is not with the FDA because the control arm is the chemoimmunotherapy. But that's also over 400 patient enrollment demonstrate our capability in the clinical operation. And GLORA-3 is the AML combo with aza versus aza alone. We are in the final stage of closing the enrollment. The GLORA-4, obviously, in the high-risk MDS, many people watching closely. I think there's a few key points also important this year. One is this is the front line, okay? The frontline patients with high-risk MDS. In the trial design, similar to the [indiscernible], the combo with aza versus aza alone. And this has been cleared by FDA, EMA, PMDA and China. And globally, not because [indiscernible] failed, but also another Bcl-2 inhibitor [indiscernible] is not on the MDS, not on the registration trial. And globally, we are the only Phase III registration trial for the high-risk MDS. There's no target drug approved in the high-risk MDS in the last 20 years. So this remain globally unmet medical need. And enrollment is doing well because experts around the world in MDS are really enthusiastic or want to help patients with high-risk MDS. So overall, I think to summarize, we anticipate, as we said before, the enrollment for GLORA-4 and POLARIS-1 plus 2 could complete by late this year or early next year. And the good problem to have, we're looking for potentially 3 NDA to file the second half of next year.

Great. And if I can squeeze one more in. Just for the BTK degrader 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 a benchmark -- internal benchmark of efficacy early on?

Yes. I think you all know that the BTK as a target is very competitive, very crowd, and there's many inhibitors, covalent, non-covalent on the market and some are doing very well. But the BTK degrader do have advantage, at least with some of the current up to even Phase III data. So we conduct carefully preclinical data to show our drug, 3288 versus other 2 from [indiscernible] or B1 that have more -- better selectivity and stronger efficacy. But that, again, is in the preclinical setting. Currently, I think in the Phase I, we're moving along very well in terms of dose escalation for safety. But more importantly, first, those are all BTK exposed patients, okay? It doesn't matter covalent or noncovalent. And we want to show some response in those patient population first, right? That's important. That's 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 -- most importantly, combination with our Bcl-2 inhibitor. I think the one example in that setting may be the DLBCL. So because so far, the BTK inhibitor hasn't shown good activity as a single agent in that DLBCL setting. And of course, there are also a lot of data that combined with Bcl-2 may have better readout in this patient population. Another potential one, but we don't have data to share yet is in the non-oncology indication. I think there are many autoimmune indications could be benefit with the BTK degrader.

Your next question will come from the line of Biren Amin with Piper Sandler.

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.

We just address the same question. Let me repeat that. So currently, we will very actively enroll patients and plan to complete the enrollment either by the end of this year or the early next year, plan to submit the NDA next year.

Yes. I think just to add a little bit for the POLARIS-2, the filing NDA is 6 months MMR rate after the last patient in. So of course, we already demonstrate very strong data in the MR rate for this patient population, and we are confident on that. But the key, of course, is to finish enrollment. And for the POLARIS-1, the filing of NDA with FDA is the 3 months MRD negative CR rate. So I think, again, the target enrollment is on track. And with the 6 months or 3 months endpoint for the NDA filing, we are looking for potential filing of those 2 NDAs second half next year.

Great. And maybe just a 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's the first question on the global license. And then 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. And then 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 answer your last question first. So the 3288 is still ongoing in the Phase I trial, U.S., China. I think because this is a dose escalation and the cutoff for the ASH already ended. So we don't anticipate to present the Phase I data this year at ASH. But the progress are doing well. Perhaps we can have some to share maybe EHA next year in terms of timing for the Phase I data. And again, we are conducting several autoimmune indications to demonstrate good preclinical activities. And because the non-oncology trials, in the Phase I healthy volunteer, you do need a placebo control, right? So that's where we are working with to getting IND filed for the non-oncology indications, including the MS. But that data will come from a little bit behind because of making the placebo control. But we do anticipate the IND to be filed soon with the autoimmune indications. And for your first question, I think that the Takeda deal, as you know, that we entered the global exclusive partnership option agreement 2 years ago, 2024. And that is, again, exclusive, global outside China and some territories. And for that, Takeda back 2 years ago, paid $100 million upfront and $75 million equity investment. And there's also a total up to $1.2 billion aggregate when they exercise the option and a certain milestone payment. And also the tiered royalty rate from 12% to start up to 19%. I think globally, Takeda is a key player in the CML and AL after Novartis, obviously. But I think we do believe Takeda is important and a global partner for commercialization of olverembatinib. And one of the main reasons for the option agreement is obviously to have a competitive product ponatinib and potential antitrust issue. But ponatinib patent will expire early next year. I think that's the key component in the option excesses. And also, we do work closely since the option agreement signed with the Takeda team. So 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 think we do -- I mean, still have a second half 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's not just the number, 400 staff in the commercial team, but more importantly, it is to cover 80% of the market potential with the product -- two products in China. I think that's 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.

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

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? And 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.

Really great question. But first, based on the preclinical data, our drug is probably among all the TKIs or allosteric inhibitors, the most potent one against the [ T31type ] mutation and also the compound mutation because in the BI gene, the mutation not just happened in one hotspot. The [ T315I ] is considered a gatekeeper mutation, differentiate those in terms of third-generation BI inhibitor. But on top of that, there's also the more than one mutation called compound mutation in the same cell, okay? And currently, asciminib and also those turns or 11 do not have those strong data. So olverembatinib is the most potent one and also most active against a wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of late-line CML patients. So currently, even though asciminib have approved label with only U.S. to treat the patient with [indiscernible] mutation, but they need a 5x dose, right? 5x dose and also in U.S., that's 5x the cost, almost $1 million. So I think that in the late-line CML patients with mutations, we do show probably the most potent one, okay? And 11 or 701 now with Merck do not have those data, and they also are mostly in the early Phase I or II. And in the U.S., because of Project Optimus, we have those data 4 or 5 years ago with MD Anderson that we have patients basically unmet medical need, right? Patients who fail both ponatinib and asciminib are the patients with no other treatment options. But because of the project Optimus, FDA do not allow the single-agent, single-arm pivotal Phase II trials for the registration. That's why we have to conduct the RCT. We have to have the control arm like [indiscernible]. I think 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 VR inhibitor to a patient who failed after first line early, right? You don't want to wait after 4 or 5 line. You want to give the strong one. So the CML patients who achieve deeper response like MMR, MRD negative CR or the MR4 or DMR 4.5. So patients who can achieve a deep response early would be able to achieve TFR. And in certain cases, may be drug-free for many years, defined as a clinical cure. I think that's important. That's why we have a second-line data. We have the real-world data prospective comparative study to demonstrate the olverembatinib could be the choice of patients who fail the frontline. It doesn't matter it's a TKI or a cinema or any other allosteric inhibitor. That's the goal. That's the key differentiation we have been showing -- presented with the clinical data.

Your next question will come from the line of Gregory Renza with Truist Securities.

Congrats on the progress. My question just to start is just on lisaftoclax. Certainly, when it comes to the commercial trajectory over this year, could you just comment about how that perhaps changed since [indiscernible] 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? And maybe just comment a bit on the 5A ramp-up, as you've mentioned, how that's perhaps translating into more measurable real-world advantages in China?

Okay. Great question. So overall, [indiscernible] is a very tough target, right? And we have been working on that in the lab for 30 years, clinically for 21 years, advanced 3 products in the clinic, but only the lisaftoclax made to the market. But again, compare -- we always compare with the [indiscernible] 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 that in the CRLSL patients, some of the early risk was in the tumor lysis syndrome. That's why venetoclax and also [ lisaftoclax ] went to this weekly dosing now, right, and require hospitalization and close monitoring because of tumor lysis risk. But on the other hand, because venetoclax is already on the market, same with venetoclax now, the differentiation in the chronic dosing patients like CLL is actually the safety, right? If the drug tolerated well with less tumor syndrome, less bone marrow toxicity, primarily in our case is we have a shorter [indiscernible] that translates into better safety profile, less neutropenia, thrombocytopenia and also much less infection. Some of the hematology malignancy patients in the clinic presented first is actually the infection, like high-risk MDS, right? And then they find 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 a lower risk of DDI drug to combine with, right, not just combine with azacitidine standard of care for high-risk MDS right now, but also in some cases of marrow disease, especially the multi 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 [indiscernible] 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 convening, 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, Dr. Yang. And 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 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?

To be honest, it's hard to say which one is all data-driven, right? But to your question, we are really happy to see we demonstrate clinical benefit in the pediatric soft T-cell tumor setting, combined with, in our case, Bcl-2 inhibitor, right? So one of the challenges for the MDM253 target, that's why currently no approved product yet, is this negative feedback loop and also the requirement of 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 though from the competitive product, the [indiscernible] compound also entered the Phase III registration trial with the add-on strategy of a JAK inhibitor in MF. And obviously, it's encouraging to see Ipsen entered the acquisition with potentially $1.75 billion. I think there is a potential maybe at the end of the tunnel, see that finally MDM253 inhibitor may enter the market or registration path. For your question, I think among the pipeline, we have five of them right now. Each one of them have a unique different strength differentiation based on the current data. Obviously, the two new ones, the EED inhibitor 5918, we will show the data at ASH this year. We have completed close to 100-patient Phase I trial in lymphoma setting. We are very excited to show this data at the upcoming ASH that's already submitted. And for the EED inhibitor, there's also potential in prostate cancer in some other settings of solid tumor. I think there's a lot of potential in the EED. We are the first one in China, globally, the second in oncology setting. And I think there are a lot of potential in the EED in both heme and solid tumor. And of course, the BTK degrader 3288 is also very exciting in terms of oncology, non-oncology. I think they currently, in addition to the two approved products in China, globally for registration trial, clearly the focus, right? We want to getting the first NDA filed with the FDA on those two products. But as you can see in the 5 clinical stage assets, at least those 3, 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 in favor, it's hard to say. It's all data-driven. But I think all these 3 do have really exciting data and the path to registration.

Yes. And maybe just to add to that, as it relates to our presence in China, our legacy in China, we have -- we're one of the few companies that can derisk 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's important to keep in mind about us.

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

I appreciate the helpful detail. A couple of quick questions on [indiscernible]. I think you were talking about failure patients development being explored. Could you maybe just touch on how quickly you can generate data there? What does the patient pool look like? And then on GLORA-4, if you could maybe comment on your expectation for CR rate and PLS and how maybe the interim OS analysis would be handled in the study if you -- if there's anything early built in there? And then I have a follow-up question on POLARIS.

So the first question, I think maybe Yifan can answer.

Very great question. Yes, based on our preclinical data, we have reported using receptor class in combination with olverembatinib able to overcome venetoclax resistance, which we have previously reported at the ACR. We also use very preliminary data we submit to this year ASH. And when the data mature, we have data demonstrated combo able to overcome the venetoclax resistance. The data is preliminary, but very exciting. We submit abstract to ASH. So that's just your question. We -- in the process in -- globally, including in China or outside China in U.S., and we try our best effort to try to enroll more treatment patient population using different strategy based on the known resistance mechanism to target this resistant AML population, either using the combo or our other compound, APG-1252. To address your question on GLORA-4 study, as we mentioned, because this is a double-blind randomized study, we cannot analyze the data early because the enrollment is still ongoing. But as we -- 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 inhibitor, we were able to submit the NDA and using the CRA as the primary endpoint and then continue to mature the OS data sometime next year.

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

Very good question. So based on the current study design, at the beginning, actually FDA denied our study design to allow patients crossover from the control arm to the investigation arm. But later on, we try again to request the FDA finally that we might allow those patients fail from the control arm crossover to olverembatinib. So that will make the study more attractive, number one. Number two, regarding the endpoint. So currently, we use the 24 weeks at the 24 weeks MMR rate as the primary endpoint. So the basic study design is the power enough and double the MMR rate compared to control arm.

And also just to add one, the design of the POLARIS-2 in terms of -- because of the project Optimus, right, 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. So -- and also allowed the crossover, okay? And remember, the POLARIS-2 also have the Arm B, the mutation with T31 mutation patient only that we can do the single-arm design with 48 patients, okay? So I think that the total POLARIS-2 is 333 patients and enroll well and then the 6 months MMR rate for the initial filing of the NDA with the FDA.

Awesome. And last one for Veet, if I may. Just if you could comment on your OpEx trajectory, and if you're getting to a 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.

Yes. Great question, Mayank. So as I said, we reaffirmed our cash runway, and we're happy that we've been adhering to our forecasted spending given the scale of our studies globally, multiple countries. And we're at a point now, what we wanted to do for this year was to derisk the balance sheet in 2025 so that we can execute on enrollment. And this year is the year of execution. Enrollment is going well. Dr. Yang and Dr. Zhai discussed that. And so I think as it relates to the expenses for the studies, we're now -- given we're at the late stages of enrollment, we are now kind of at the peak as it relates to OpEx spend. So all that is going as planned and expected. And 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. So those are the key expected milestones we have with the cash in our balance sheet.

Your final question will come from the line of Michael King with Rodman & Renshaw LLC.

Congrats on the progress, guys. Maybe I wanted to drill down a little bit further on the balance sheet question. If you could talk a bit about -- a little further about capital allocation because you guys do have a fairly hefty burn rate. And even with the Takeda opt-in, it's still -- you're going to require a lot of capital in highly competitive markets, even with differentiated products, you do have entrenched competition. So I'm just wondering how -- 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.

Yes. Maybe I can start or go ahead, Dr. Yang.

No, no. Veet, go ahead.

Yes. In terms of allocation of our total budget to programs, we haven't 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. So obviously, that's what we wanted to establish. What we have done is with the dual listing steps we've taken is allow ourselves, we believe, within as reasonable as possible, maximum 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've allowed ourselves to hopefully deliver on catalysts, gain value and thereby have less dilutive sources for raising capital going forward. And of course, with Faical on board, the optionality as it relates to potential partnerships when it makes sense as well. So we are not in a pressure for one particular path, which is exactly where we want to be at this point.

Yes, I think I fully agree. I'll 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 registration trial and 4 global cleared by FDA and EMA, majority of the enrollment are already done. That's why you see the first 6 months, we have R&D expense 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, right? 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 to grow revenue with two product sales in China. I think we are really unique is 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 revenue as well.

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, positions us well to be the global player in the heme malignancies. And more importantly, we are advanced well in terms of all the key registration trials and then with a target to complete them by the end of the year or early next year. But more importantly, we are in the position. If you look at some of the competitor or the [indiscernible] biotech company this time last year, okay? So I told my team and many investors Ascentage will be a different company by the time next year, okay? So we're 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. And thank you all for your attention and support.

Okay. Hello, everyone. Thank you guys for joining. I realize it's a really busy morning, and I didn't want to reschedule this after some of the news came out. And I figured it's -- we structured it for 10:00 a.m., and we had kind of lined up with the management team at Ascentage. So I wanted to be respectful. But like I shared in my prior e-mails that I mentioned previously as well, I think the key goal for me was to make sure that with all the M&A activity that's happened in the space, we have a good understanding of some of the other clinical-stage and mid-stage and late-stage assets programs as well.

So this company, in particular, is in the hematology space, and it's not just one because my initial interest in the company originated with some of their work in the CML space because we were spending a lot of time on Terns and on Enliven, et cetera. But there's a path beyond that. Let me turn it over to you, Veet, perhaps to introduce the management, we'll jump right in.

Yes. Okay. Thank you. Good morning, everyone. Thanks for this opportunity, Umer. I think that there are 3 key takeaway points for this discussion. High-risk MDS is going to define Ascentage as the player in this area that will potentially provide the best-in-disease drug for this global unmet medical need. Second, we are actively running POLARIS-1 in Ph+ ALL. This is the first-line global registrational study of olverembatinib. There's already available global data, including U.S., doubling the MRD-negative CR rate of ponatinib.

We have even more data in combo with blina showing oral presentation at ASCO just a couple of weeks ago by lead investigator, Dr. Elias Jabbour. Another exciting really also global registration trial is POLARIS-2 covering CML. So basically, we have 2 potential NDA filings next year after POLARIS-1 and POLARIS-2, plus the NDA for high-risk MDS. So basically, 3 potential NDA filings in 2027, then opportunities to expand multiple fold with lisaftoclax as a cornerstone asset, including with the proprietary BTK protein degrader, APG-3288.

Yes, there we go. Could you remind us on the CML molecule, where exactly are you? And is it a second-gen or a third-gen BCR-ABL? And what's novel about it?

Our asset on the CML is the third-generation BCR-ABL inhibitor, very potent against the especially T315I mutation, which is a gatekeeper defined third-generation BCR-ABL inhibitor, and also it's multi-kinase, very broad spectrum against multiple mutations in BCR-ABL, including those compound mutations.

Have you shown data in T315I?

Yes. We are probably the most potent one against T315I mutations, including those compound mutations on top of T315I.

And the MMR rate is what in T315I?

MMR rate is -- depending on the disease and the line of treatment, we have about 50% or 60%. Maybe, Umer, if you don't mind, let me first probably show a little bit of overall company. So we are actually a global commercial-stage hematology/oncology company. From day 1, our mission is to focus on global unmet medical need and for the global market. We are very proud that now we have 2 novel commercial-stage products, olverembatinib and Lisaftoclax. We are the first dual-listed company on NASDAQ and also Hong Kong Stock Exchange about 6 years ago.

We have a global issued patent over 500 and over 1,000 pending. And we right now have 7 novel active compounds in global clinical stage and over at least 30 FDA-cleared INDs. But more importantly, we have 13 global registration trials. We completed 4 of them, 9 ongoing, focused on 7 doses for global registration trials. So I think the next -- this is a little bit busy slide, but the key point is that we have global, innovative, highly derisked triple late-stage pipeline. The first product, olverembatinib, is -- olverembatinib resistance, sometimes we just call olver -- is the third-generation BCR-ABL inhibitor already approved for CML-CP since 2021 in China.

Basically, we demonstrated thousands of patients in real-world safety efficacy, especially long-term safety for some patients near 10 years now. And it's the FDA, EMA cleared global registration trial covering both CML and Ph-positive ALL. Lisaftoclax is a Bcl-2 selective inhibitor approved as single agent post-BTK CLL/SLL since July last year. So globally, as a target, we are the second Bcl-2 selective inhibitor to the market. But in terms of single agent for the post-BTK CLL/SLL, we're actually globally the first one. We have this unique daily dosing advantage, enhanced safety with low risk of.

We're also running 2 FDA and EMA cleared global registration trials. As you can see, we also have a very rich pipeline covering multiple novel targets. Some of them can be the first-in-class if tests carry out like MDM2-p53, Bcl-2/Bcl-XL, and also PRC2 inhibitor, which is an EED inhibitor, the APG-5918. We also moved the BTK degrader into Phase I U.S. and China early this year.

Got it. Okay. Great. Maybe -- can you hear me now? I just wanted to make sure we could ask you as well.

You hear me now?

Okay. Yes, we have you. Okay. Excellent. So I wanted to maybe kick things off on the CML side with the BCR-ABL. Just remind me, you're approved in China. And what's the sort of market share in China? Plus when do we get Phase III data for U.S. filing? And is that the plan?

Yes. I think that the first -- we were the first and only third-generation BCR-ABL inhibitor approved and also getting the NRDL coverage in China. So there are thousands of patients available data in the real world. We were the first and only one in the last 3 years. And last year, both ponatinib and asciminib were approved in China, but they're not getting NRDL coverage yet. So we are the only third-generation BCR-ABL inhibitor available in China. Globally, we have run the bridging study 5 years ago with MD Anderson, Dr. Kantarjian and Dr. Elias Jabbour.

And we published JAMA Oncology paper demonstrated in the U.S. data that heavily pretreated patients, we demonstrated a very robust MMR rate, okay? So these are the patients who failed ponatinib, who failed asciminib, or in some cases, patients who failed both ponatinib and asciminib achieved very excellent MMR rate. This already had an oral presentation at ASCO, ASH, published in JAMA Oncology. But more importantly, very potent against those with T315I mutations. So those patients were heavily pretreated. As I mentioned, those who failed ponatinib or asciminib or both will demonstrate excellent MMR rate.

Okay. Remind me again, timing of Phase III?

Timing of Phase III for the CML is the -- our global, our POLARIS study, okay? So we already opened more than 20 countries, over 100 sites. Our goal is to complete the POLARIS-2 for the CML-CP patients globally later this year or early next year.

POLARIS-2

Yes, POLARIS-2 for the CML, and this MMR rate is -- 6-month MMR rate is the primary endpoint for accelerated approval. So basically, we are looking for the NDA filing second half of next year.

So on clin trials, if I may. On clinical trials, it says the study should have been completed by December 2025. Could you just give us a little bit of color on the POLARIS-2 trial?

Yes, those are not actively updated. I think those were older information. But as I mentioned, we have those data in the U.S. and global, and POLARIS-2 cleared by FDA, EMA, multiple countries. This is a randomized Phase III trial as the FDA required the RCT, and with bosutinib as a control arm, 2:1 ratio, 190 patients in investigation arm and the bosutinib 95 patients. One thing important to help patient enrollment is FDA agreed with crossover late last year that helped our enrollment a lot.

Okay. And if I may, what's your expectation on -- because I think this study has 2 parts. There's a non-T315I and T315I. What's your expectation on MMR for the T315I?

The control arm in this case is bosutinib, which is not active against the T315I mutation, right? So the Part B of POLARIS-2 is a single agent, single arm with T315I mutation only, about in total 48 patients. We expect the MMR rate for this particular group of patients is probably around 50%, okay, based on our previous data. And we are probably the most potent and the one against T315I mutation or compound mutations.

Yes, that would that would put us as one of the more potent out there because even if you look at the non-T315I mutations, that number in itself would be pretty acceptable.

Yes. No, I think that's really important. And I guess as we think about some of the activity we've seen from other folks on T315I, I mean, obviously, even Terns had very limited data. But the T315I you're recruiting, are they all asciminib experienced?

Not all, but we include those experienced patients as well. We published the U.S. data, right, the patients who experienced asciminib or both ponatinib and asciminib, basically unmet medical need, and demonstrate good efficacy data, MMR rate.

Yes, that makes sense. And then also in terms of sort of -- I know you're sort of putting these 50% type numbers out there, but I don't know if you necessarily need to hit a number that high for it to be considered fairly competitive. I guess could you put that into perspective for us as well? What's an MMR number in general that will be considered fairly competitive even if, let's say, like in a 25% MMR in T315I competitive or not?

I think 25% for those who failed ponatinib, who failed asciminib probably is sufficient, right? This is unmet medical need. But for patients just one of them, right now, maybe, let's say, asciminib, right? If we can hit the 30% to 40%, I think that's also good enough.

Makes sense. Do you -- I know it's an open-label trial. Do you have visibility on whether the prior observations of these MMR rates are replicating in the Phase III as well?

That's hard to say because this is an ongoing registration trial. But our experience, these are the U.S. data, right, with MD Anderson leading PI that we do, and their own experience as well, we're probably the most potent one, especially against nowadays, more patients experience first-line asciminib. Asciminib itself requires 5x dose preclinical and clinically, and also 5x the cost, right? So basically for about 40% late-line CML patients, asciminib is not that potent.

Feasible. And just remind me, what's the dose that's approved in China? And what's the dose that's being used in T315I and the dose used in non-T315I?

The approval dose is 40-milligram QOD. And with the FDA on the Project Optimus, we can start with 30-milligram QOD in the investigation arm. And for those, if we didn't get a good response, they can move to 40. And for the T315I mutation only patients, they can start with 40-milligram QOD and then can also titrate to 30 milligram if achieve MMR.

Wow. So you're not doing that because I felt like on asciminib and a lot of the other data sets, asciminib was 40 milligrams, regular, but 200 milligrams for T315I. You're not pushing the dose for T315I?

No. We're just regular dose, very potent. Yes.

So presumably, the tolerability would be meaningfully differentiated regardless of efficacy because the dose is a lot lower in the T315I patients.

Right. Yes.

But conversely, do you think you're leaving efficacy on the table by not pushing the dose in T315I?

We don't need to. We actually -- in the ASCO, we had an oral presentation second-line data. If the second-line data with the patient in the frontline experience the second-generation TKI, actually, MMR rate is even higher.

I see.

Yes. We also -- yes, I think that speaks to your question about like the MMRs for the ongoing Phase III. We actually have real-world data to show maintaining pretty high and increasing MMR rates over cycles here.

Got it. Got it. Got it. Okay. That's super helpful. Let me transition quickly to the Bcl-2. And I know this is a target that a lot of investors are familiar with from venetoclax perspective. I know BeiGene is working on a Bcl-2 as well on the fixed duration regimen along with their BTK inhibitor. So I guess my first question to you is, where are you in your development? And how do you see -- I mean, I realize there's probably differentiation over venetoclax, which I would love to hear about. But also, how do you see this molecule relative to the BeiGene Bcl-2 as well?

Very good question. First, we have always been competing with venetoclax. The #1 differentiation is from day 1, we designed this daily dosing up, right? So because of tumor lysis syndrome in the early clinical trial of venetoclax, the approved label is 5 weekly dosing up, right? That's actually the same, even more complicated for sonrotoclax. Sonrotoclax started 1 milligram and the target dose is 320 milligram. You can see from 1 milligram to 320 milligram is 9 weeks dosing up, okay?

Can you please remind me the dose again for sonrotoclax?

Sonrotoclax started dose is 1 milligram. Also we dose up, right? So 1 milligram every day for 1 week, okay? And then the RP2D or the market dose is actually 320 milligram. So from 1 milligram dosing up to 320 milligram, that's 9 dose cohorts, okay? In the clinical trial, it takes 9 weeks or 2 months. So the approved label, they were able to squeeze that into the 5 weeks. So every week, they dose up for 2 doses, okay? So 3 days for 1 milligram, 4 days for 2 milligram, and then up to 320 milligram. So that's also 5 weeks but dose cohort dose are up, right? So that's #1, really important for patient convenience. And also, we don't need a lead-in dose when we combine with a BTK inhibitor.

Second, I think more important is that we have a shorter T1/2. That's important for this class of drug because it's Cmax driven and also is the hit mechanism, right? So we have about 5, 6 hours T1/2, where venetoclax is about 25, 30 hours, okay? So shorter T1/2 translates into better safety profile, better tolerance, okay? So we demonstrate much lower, especially grade 3 or 4 neutropenia, thrombocytopenia or febrile neutropenia, and also related to those late-stage infections, SAEs.

Another important differentiation is the drug-drug interaction, right? So among the 3 approved Bcl-2 inhibitors, we are the one having lower the risk of DDI. We are not a substrate of P-glycoprotein or BCRP. So those are important differentiations because most of the hematology oncology patients are elderly. They need to combine even like the case of BTK inhibitor, ibrutinib, they need a reduced dose. And also in the case of antifungal drugs in late-stage infection, those are the concerns, right?

So those are key differentiations. But I think more importantly, as we are in 2 FDA, EMA cleared global registration trials, GLORA and GLORA-4. I think we are most excited, also important impact globally is about the GLORA-4 study. So I don't know, we can have the slide on the GLORA-4 global Phase III registration trial.

I think that's...

Okay. I think that first, we have to realize that globally, FDA, there's no target drug approval for high-risk MDS, right? There's about 10-plus for the AML, but 0 for high-risk MDS so far. We are the only global Phase III registration trial on high-risk MDS. Sonrotoclax is not on MDS either, okay? They are doing that. As you mentioned, the registration trial combo with theirs is only in the CLL, okay? So they are not in AML or MDS for sure.

And AbbVie failed in the VERONA trial announced last year. So we are the frontline for the high-risk MDS. This is very important, right? This is a frontline patient registration trial and no competition, okay? Basically, the VERONA trial is not on the MDS. So we are the only global Phase III registration trial. And we just had a really excellent advisory board meeting at EHA globally, most MDS experts are very excited about this trial. They all want to help patients with MDS globally. Enrollment is moving very fast and very well. So we're looking for potential completion late this year or early next year. And again, potential NDA filing in 2027.

Got it. NDA in 27. Okay. There's a few trials that investors want to clarify on this, so I want to make sure we go through. Let me just go step by step. #1, can you walk us through the data, maybe put up the slide on this for the Phase 1b in high-risk MDS, what the prior treatment was, the duration of treatment, how many patients, CRs, and if there was any myelosuppression seen?

Yes. I think that we published this and actually had an oral presentation at ASCO 2 years ago. Those are all U.S. or Australia data, okay? So, 2 important data, right? First, just to focus on the high-risk MDS. We show the ORR in newly diagnosed MDS patients, 80%, okay? And the CR rate, about 40%, okay? I think that those are very impressive data. Second, we also took the venetoclax failed AML patients, okay? The naive patients, about the same efficacy, okay? But more importantly, we have venetoclax failed AML patients. We got an ORR about 31.8%, okay?

I think this actually was surprising, right, because the same target, same pathway, how come failed the AML patient, they work. I think in terms of ORR, we have realized that most of the Bcl-2 inhibitor resistance mechanism is not because of new mutation, but because of the MCL-1 upregulation, including also the Bcl-xL. So, basically, the downstream pathway is the one causes the resistance, okay? So, we did the resistant cell line exposed to lisaftoclax. We did the profiling analysis. Actually, the downstream profiling are not exactly the same. So, this maybe explains why lisaftoclax works just combo with aza in venetoclax-failed patients.

But I think in the real world, we want to get it better. That's why we also have clinical data, planned the trial to combo with our olverembatinib because it's a multi-kinase inhibitor and also can downregulate MCL-1. So, we already demonstrated excellent data, including those presented at EHA just last week for pediatric Ph+ALL. So, we demonstrated excellent safety and some efficacy early data, excellent efficacy data in combo of olverembatinib with venetoclax.

But just so I'm clear, the Phase III that's ongoing is azacitidine combo, correct?

Yes. Yes.

Okay. And this data we're looking at here was not aza or it is aza combo as well. Okay.

Yes.

Okay. Excellent. So then I think that's maybe a good segue then into -- could you just give us a sense for how your monotherapy have looked versus azacitidine combo?

The efficacy of in the AML, the overall CR/CRi rate is about 72%, okay? And MRD.

Monotherapy in AML is 70% to 72%.

Yes, in the combo with aza.

Monotherapy.

The AML, you have to combo with aza. That's aza is a standard, right, for AML, MDS. So everybody have to combo with...

What about MDS as monotherapy?

They have to combo with aza as well. That's also considered is the standard of care aza for MDS. So the combo with aza is considered like a single agent.

Have you ever run monotherapy...

I don't think that it is allowed, right, because the aza is a backbone for AML or MDS, although the ORR CR rate is low. So you have to -- especially in the high-risk MDS, you have to combo with aza.

Got it. So in the Phase III that's ongoing, GLORA-4, which is aza add-on versus aza monotherapy, what do you expect aza monotherapy to do on the primary endpoint? And what do you expect the active arm to do?

Excellent question. And based on all the data and the real world, aza alone in MDS, ORR is probably about 30%, okay? CR rate is about 15%, okay? So those are the consistent data across the countries, okay? So we have demonstrated that combo with lisaftoclax, we can achieve ORR 80%, CR rate, 40%.

So 80% for ORR, you're saying?

Right.

Okay. Got it. And give me 1 second, let me just make sure...

More than double the aza, right?

Yes. But the primary endpoint is overall survival. And would you have survival data by next year?

Excellent question, Umer. So the FDA required OS for all the AML/MDS trial, right? So -- but we have discussed with the FDA. And last year, they agreed CR as your primary endpoint. And so the CR can be used as accelerated approval. I think that's really excellent news. That's important. And of course, the OS will be required for full approval. So I think that's maybe I forgot to mention. The reason we can say we can have NDA filing for accelerated approval, that's based on the CR rate next year.

Okay. So basically, you're saying you can more than double the aza CR rate. Is that reasonable? You're saying mid-teens and you can be at least 30% plus. You're thinking 40%, but even if it's 30%, that's doubling of CR rate. And doubling of response rate. What's your expectation on early hazard ratio on overall survival when the CR comes out? I realize it will be immature, but what would be the rate? Do we have 10% death or 20% or 30%?

That's hard to say. But I think that the -- let's focus on the primary endpoint, right, CR and OS, right? CR for approval and the OS for the full approval. But more importantly, I think we have to realize that the high-risk MDS, there's no target drug approved in the last 20 years, a lot of challenges, right? This is almost as difficult as pancreatic cancer.

Yes, makes sense. One last thing. Could you remind us the last time you showed data for HR-MDS was at ASCO 2025 or at EHA, was there an update?

We had an update but not the GLORA trial, but we have an update in the MDS or AML patients in the real world at EHA and also the combo with olverembatinib in Ph-positive ALL patients. And olverembatinib alone in the Ph ALL, we can double the MRD-negative rate, right? And also combo with blina, we got almost 100% ORR. And more importantly, high MRD, 80% MRD-negative rate. But in terms of in the MDS, AML, we actually demonstrate the real-world data, again, for patients who failed venetoclax in the high-risk MDS and the bridging makes sense to the CAR-T as well.

Makes sense. Makes sense. Makes sense. Okay. Excellent. Again, CR data by mid next year, late next year, what's the timing?

I think probably both are possible.

Okay. The second half.

Yes. You mean for the GLORA-4, right, MDS...

Yes.

Hopefully, mid next year.

Okay. One last thing. I know we're out of time, but I do want to touch upon the BTK degrader pretty quick. When can we have data? And why do you think you wouldn't have as much of a bleeding issue?

First, we are in Phase I in U.S. and China. And we got this from pre-IND to IND in about 8 months, okay? Based on the preclinical data, we compare both BeiGene and Nurix, we are more selective, more potent. And of course, I cannot answer for your question about bleeding right now. But I think based on the preclinical data being more selective, probably important. And another, of course, for us is the combo with our best Bcl-2 inhibitor, lisaftoclax, right? So there are many BTK inhibitors and degraders out there. But I think for a lot of including the fixed duration CLL or tough to treat DLBCL, maybe the combo of a BTK degrader with a better Bcl-2 inhibitor would be impact and help patients as well.

Excellent. Excellent. Excellent. Veet, anything we missed? I want to make sure we catch anything we may have missed.

No, I think, Umer, is just -- I think as the CFO of the company here, I'd say there's a disconnect in value here that we're experiencing in the market. And I hope what Dr. Yang shared in terms of our momentum here and our layout as a company, we're a fairly sizable company. We're over 820 employees right now, over 130 of which are in the U.S. And we're looking to -- I'd say we have a very strong clinical team in the U.S. execution and the long history of execution. I'd say we have everything here in the U.S. but commercial, and that's something that's kind of the next chapter for us.

Yes, outstanding. Thank you guys for making time.

Thank you.

Thank you so much.

Thank you very much.

Good day, everyone, and welcome to Ascentage Pharma's 2025 Annual Results Earnings Call. [Operator Instructions] As a reminder, today's call is being recorded.

Thank you for joining us. I will now turn the call over to Yuly Chen, Senior Director of Investor Relations for the safe harbor statement. Yuly, 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, Cofounder, Chief Scientific Adviser, 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 and CEO of the company. Today, I'm very happy to present our 2025 full year financial results and a 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 totaled $82.1 million. Our year-end cash balance is about $353.2 million, cash runway through 2027.

I think 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 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, 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 the Phase III registrational stage.

POLARIS-1 for the Ph+ ALL, the Phase III registrational trial also received clearance globally, including FDA, EMA and CDE. Part 1 data also reported at ASH demonstrated strong 64% and MRD-negative CR rate in the first-line Ph+ ALL. Olverembatinib granted Breakthrough Destination for the first-line treatment of Ph+ ALL by CDE. We are also very proud to have FDA and CDE IND clearance for our novel BDK degrader APG-3288. Both Lisaftoclax and Olverembatinib entered 2025 CSCO Guidelines. 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. And also, we published many peer-reviewed top journals. I think here is our summary of world-class innovative, highly derisked and super late-stage pipeline. We have the list of 7 novel compounds. The first 2, Olverembatinib, as a novel third-generation BCR-ABL inhibitor and Lisaftoclax as the novel Bcl-2 Selective inhibitor. Both have been marketed in China and also entered for global registration trial cleared by FDA, EMA, and total, we actually have 9 registrational trial for multiple indications.

We also have several novel potentially first-in-class compound targeting such as the FAK, ALK, ROS1, triple kinase and MDM2-p53 and the dual Bcl-2/Bcl-xL and the PRC2 third generation like the EED inhibitor. And more importantly, we have newly cleared Phase 1 novel BTK degrader, APG-3288. All of these are running the trials in U.S. and China and in multiple countries, mainly focused on hematology/oncology, but also have a potential and also in the clinical stage testing in indications such as anemia.

So we have built a very large commercial scale in China with a dual product approved especially for our Bcl-2 Selective inhibitor subclass was ahead of our schedule last year. And with the 2 commercial products, we have built over 270 by the year-end commercial team, covered 1,500 hospitals and more than 800 DTP pharmacies. I think our Dual-Engine strategy working well. As you can see, our last year commercial revenue, I think that's a transition for Ascentage from being rely on the investment -- investors and also BD income to the last year, 100% sales of the commercial stage product.

I think that, that's a really important transition for the company to be able to self-sustain with our own revenue to support our own R&D program. If you look at just Olverembatinib alone, we have a strong sale following full NRDL listing covering CML with and without mutation. So if you look at the total sales, reaching $62.2 million, that represents 81% year-over-year growth and we will continue to cover more hospitals, DTP pharmacy and also a broader reach to the Tier-1 hospitals. And with the full NRDL coverage and also translating into very long DoT that will support sustained growth as the patients continue to use our drug over a long time.

If you look at Lisaftoclax, first, this July approval was ahead of schedule. And we built a very fast and full functional commercial team dedicated to Lisaftoclax. So the seamless go-to-market strategy using the national commercial infrastructure really helped us to rapidly expand the sales force and hospital coverage. So just the first 5 months, we have reached more than USD 10 million sales. This is, I think, is among top, at least in the hematology oncology product sales in the first couple of months in China.

And then let's go to the R&D highlights. First, let's look at our Lisaftoclax is actively advancing its global Phase III registrational trials. First, our approval as a single agent for CLL, SLL, after BTK inhibitor is already represented the first label for the Bcl-2 Selective inhibitor. As you know, venetoclax was approved 2016. And continually, the only single agent was limited to the 17p deletion, CLL and SLL. The other CLL, SLL is all combination with CD20 antibodies. Our GLORA, GLORA-2 and GLORA-3 also received FDA, EMA and CDE clearance. And 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 -- I mean, received the FDA, EMA and the CDE clearance, will continue pushing forward all these important global Phase III registrational trial.

I want to share a few important clinical data with you. First, with the single agent approval, based on the CC201 registrational study, those patients actually have a much poor baseline characteristics. First, the CDE actually give us a very high bar about 4, 5 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 complex karyotypes and also many have multiple mutations. So 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 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 ASH. If you look at our ORR as a combination with ASA, in the naive, the newly diagnosed AML patients, we achieved ORR 83%. And more importantly, in some cases, about 22 patients who have failed venetoclax, we also achieved 32% or in the MDS, we have in the newly diagnosed 80%. And in the second line, our MDS, we have 50% or I think based on those excellent data and many other clinical data, FDA gives us clearance to conduct global Phase III registrational trial as the first line for the high-risk MDS. And this has been cleared by FDA, EMA and CDE and among close to 20 countries, regulatory agencies. So we are actively enrolling patients in U.S., Europe, China and throughout the world.

So if successfully carried 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 is no targeted therapy approved in the last 20 years. And current therapy have much poor efficacy and 5-year survival rate for high-risk patients is only about 16% to 24%. We are also very proud these global efforts leading by Dr. Garcia-Manero from MD Anderson and Dr. Xiaojun Huang from Peking University People's Hospital and many, many excellent expert PIs for MDS around the world.

Based on the public information, we want to highlight a few key differences of our drug versus venetoclax or sonrotoclax. If we 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. So if you look at the SAE incidence is much higher for venetoclax or sonrotoclax and the infection rate also significantly higher. So that's consistent with the clinical observation that Lisaftoclax have a better safety profile, better tolerance. And more importantly, we have a better drug combinability. CLL/SLL patients often are elderly and immunocompromised with frequent infections.

Commonly used antifungal drugs are strong 3A4 inhibitors but does not affect our Lisaftoclax PK. So if you look at the PK variability in combination with some strong 3A4 inhibitors, I think that the impact for Lisaftoclax is minimal for other two drugs either need to -- about 8x or 11x need to be adjusted dose if they are combining those. That will strongly affect clinical combination studies. And also look at the P-gp or BCRP substrates or inhibitors, Lisaftoclax is probably the one of a minimal risk in those combination studies. No need to adjust dose with like many BTK inhibitors. I think that those are very unique advantage for Lisaftoclax as the Bcl-2 Selective inhibitor.

I also want to highlight a few important progress made and the summary here for Olverembatinib. Olverembatinib is approved with full coverage by NRDL. We see excellent commercial coverage and the revenue growth last year. Globally, we are conducting POLARIS-2 for the CML and this single-agent study RCT with the bosutinib control arm also received FDA, EMA, CDE and the PMDA clearance. So 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 and this is also cleared by FDA, EMA and CDE in China with a breakthrough destination. Part one of this trial, the same trial design data was presented at ASH. And you can see the data from next couple of slides.

First, in the Part A of the Phase III registrational trial in combination with low-intensity chemo as the 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 but this actually is among all the BCR-ABL inhibitors, the best one. So we actually almost double the currently the best BCR-ABL inhibitor for the same patient population and also demonstrate very well safety profile.

Another data is looking at a potential second line treatment for the CML-CP patients. This also, again, presented at the ASH last year. We can achieve more than 50% -- I mean, 70% CCyR rate, more than 40% MMR rate and also have a really durable sustained response. Another important is in the blast crisis of the CML. I think we demonstrated in more than 64 patients with blast phase and also some serious cytogenetic abnormalities and complex karyotypes. And those patients did very well and 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. And in this case, it's actually in the pediatric patient population that is a first-line regimen in the Ph+ ALL demonstrated really excellent efficacy and safety profile. I think that this would be really important for some of the patients to receive the chemo-free and the 2 orally active agent with a long-term benefit. Olverembatinib as multiple kinase inhibitors also demonstrate clinical benefit for some rare hematological malignancies such as very hard to treat myeloid/lymphoid neoplasm with the FGFR1 rearrangement. And this actually takes a while to recruit those patients, but most of them achieve excellent response clinically.

And 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 CDE. And based on the preclinical data, I think we also did a comparison with B1 or Nurix BTK degrader demonstrate good selectivity and potency. And we're pushing forward this compound in U.S. and China for multiple indications.

I think in summary, Lisaftoclax has a very safe and potent Bcl-2 Selective inhibitor, some refer Bcl-2 inhibitor as a small molecule of PD-1, that really means it has multiple indications and also opportunity for multiple combinations. But I think more importantly, we're probably globally the only company has not just the Bcl-2 Selective inhibitor, but also Olverembatinib representing the best third generation BCR-ABL inhibitor and 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 a multiple B-cell malignancies among many hematological malignancies.

Lastly, I think I will turn the financial results to our CFO, Veet. We also go to the Slide #28.

Thank you so much. Yes. So 2025 was a successful year for us as we established our commercial strength with now 2 approved novel oncology products. In 2025, our total revenue was USD 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 USD 62.2 million represents year-over-year growth of 81%. Sales of this product reflected first full year -- 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 5-month 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 USD 130 million to USD 163 million year-over-year, which is tied to advancing ongoing global pivotal studies represents a 20.1% growth rate to support trials ongoing to -- that are expanding and moving forward. In addition, the increase in S&D expenses, sales and distribution in 2025 from USD 27 million to USD 51 million was primarily driven for sales force expansion ahead of commercial launch of Lisaftoclax, which is an efficient use of capital. So as you can see, the increase in these 2 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 USD 353.2 million compared to USD 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 $322.6 million. So 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, Veer. I also want to present our clinical catalysts and milestones for 2026. On the clinical development side, our major focus will be an advanced enrollment for the GLORA and GLORA-4 registrational trial and also advanced enrollment for Olverembatinib in terms of POLARIS-2 trial and also POLARIS-1 trial. I think as we mentioned earlier with our team, I think the keyword for 2026 is really the enrollment and enrollment. I think we'll do our best to achieve a complete enrollment and then be able to file NDAs in 2027.

We'll continue to push Degrader APG-3288 global Phase I study in terms of safety, tolerability, PK and potential efficacy data and then 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 U.S. and in China as well. But I think the major in terms of milestone for the clinical development are those highlighted here.

On the commercial front, we will continue to drive the sales growth for our Olverembatinib and also the Lisaftoclax to the Tier 1 hospitals and more pharmacies. And for Lisaftoclax, we will do our best for the benefit of patients, especially CLL/SLL, together to the NRDL coverage in China in 2026.

I think that the key driver for Ascentage to be a global player in hematology/oncology is really driven by the 2 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. I think 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 registrational studies. I think 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, I think with the patient-centric innovation and global breakthrough therapies and with currently 7, we'll call the 7 magnificent, 7 active compound, 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. And now we will be happy to answer any questions you may have. Thank you.

[Operator Instructions] We will take our first question. The first question comes from the line of Brian Chang from JPMorgan.

Maybe just first, Dr. Yang,you talked about how this year is really about on enrollment, enrollment, enrollment. 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 those indication, how should we think about the next data milestone at the upcoming medical conferences later this year?

Thank you, Brian. Very excellent question. I think let me maybe address this in 2 parts. First, for the GLORA-4 MDS, high-risk MDS, we are very happy to see this Phase III registrational trial protocol receive clearance by not just the FDA, EMA, CDE and also among close to 20 countries regulatory agency. And this is the first-line treatment for the naive -- treatment naive newly diagnosed high-risk MDS. And more importantly, this is now really the only Phase III registrational trial in the high-risk MDS globally. And we are very happy to receive the support from the PIs around the world, and they're really enthusiastic for this clinical trial to help patients globally with MDS.

And with the POLARIS-1, this is the first-line Ph+ ALL. As you know, we also presented Part 1 of the same protocol data at ASH. The 3 months MRD-negative rate CR is 64%, almost double the ponatinib and the same patient population, about only 34%. So I think that those 2 registration trials are both for the first-line treatment, which will actually much easier enroll than some of the late-line protocols. And of course, also have a huge potential market return. And with those 2 first-line treatment, and you can see MDS, we are the only one front runner in the Phase III registrational trial globally. There's 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. So I think the enrollment are doing well. And even though those only initiated late last year, but we see so far very excellent enrollment and very strong support from the health care providers around the world. And POLARIS-1 only require 3 months MRD-negative CR rate as a primary endpoint. And also, we have a strong support from FDA and all the regulatory agencies to support the protocol of the GLORA-4. I think the -- overall, we will do our best to achieve complete enrollment. And with the current time line and the primary endpoint, we anticipate to the best we can and then to be able release the top line data or complete enrollment and then be able to file NDA in 2027.

Got it. And 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? And then perhaps we actually have a follow-up after this.

Yes. Maybe for the commercial part, we can have our Head of Commercial, Zhichao to address the part of your question first.

Yes. Okay. Thank you for the question. And if you look at the actual driver of growth in 2025 in China, I believe there are several key drivers. And first of all, if you look at Olverembatinib and which really benefit from the broader reimbursement support, the affordability after NRDL inclusion, right, which Dr. Yang also mentioned and also very strong patient affordability improvement. And second, if we look at our annual report, we continue to expand the hospital and D2C pharmacy access with more than 800 hospitals and DTP pharmacy, which significantly improved the accessibility by the year-end, which also includes more than 355 hospitals with formulary access. Hospital listing is very important in China market.

And third, I believe if you look at Lisaftoclax which was approved in China and since July, and we got sales for 5 months. And Lisaftoclax, I mean, really give us a second growth engine after launch and generating more than RMB 70 million in the first 5 years on the market. And fourth, I think we scaled our commercial organization and Dr. Yang and Dr. Veet both mentioned, we scaled up our commercial organization meaningfully. Our team actually almost tripled compared to 2025 -- compared to 2025 compared to 2024. And 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 the last year's commercial growth. Thank you.

Great. And then maybe just lastly, I 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? And then 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? So if not, maybe let me try to answer your question. So first, we have conducted very thorough, of course, currently preclinical data to compare our BTK Degrader with B1 or Nurix. I think based on this comparison, we selected our candidate compound moving into the Phase I. And based on the preclinical data, at least, we show better selectivity and also more potency. That's number one. Number two, I think as the BTK is a validated target, the BTK Degrader can take care many of the BTK inhibitors covalent, non-covalent mutation or not basically have 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. So the combination of BTK inhibitor or degrader and the Bcl-2 inhibitor could really offer some of the hard-to-treat patients benefit. And in the case of the CLL/SLL, at least with the fixed duration is really potential even in 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 patients with the CLL/SLL. And in combination with the Bcl-2 maybe also can treat some hard to treat like DLBCL.

I think 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. I think with all those 3 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.

Your next question comes from the line of Biren Amin from Piper Sandler.

Maybe to start for Olverembatinib, what is your market share in China versus the Asciminib and Ponatinib. And which CML patients are you seeing the most adoption? And then I guess for second half 2025, sales grew by about 7% versus first half '25. What can we expect for the growth rate for Olverembatinib in 2026?

Really good question. The 2025 was the first year for the NRDL coverage and especially for with/without mutation. And so the patient population compare our first approved indication with T315 mutation only, we -- the patient population will more than triple. 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. And in certain better economy, the countries, I mean the province, the reduction payment can be reduced by 90%. So that's really significant as this patient is taking the drug in a long time, right, very good long DOT. So the NRDL coverage in China for the CML patients, we see really benefit -- important benefit.

The patient population in China as other late-line treatment, like you mentioned asciminib or ponatinib, both were only approved last year, okay? But they don't have any establishment or the data from China. We also have last 3, 4 years market use, even though for small dedicated mutation patient population. But overall, the physicians and the patients are really well educated position once they get into the full NRDL coverage. For both asciminib and ponatinib, they were not under NRDL coverage, okay? So that also limits the use of those 2 drugs only got approved a year ago. So there are not really much sales affordability for those non-NRDL coverage, the asciminib or ponatinib in China.

Then moving forward for 2026, we see the benefit of NRDL will continue as the price is good for 2 years. And if we 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 falling into the category with a strong support by the NRDL. And also, 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. But at the same time, because they are not officially into the NRDL coverage, so currently, in those patient population, we still want to finish our registrational trial, be able to get into the NRDL. So moving forward, I think there's a continued expansion and the growth of the revenue for Olverembatinib in China, both CML and the Ph+ ALL.

And 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 $6.7 billion. How do you think Olverembatinib would fit into the emerging treatment landscape in the U.S. for CML. And then second question, which of your global pivotal trials across both Olverembatinib and Lisaftoclax? Can we expect to see data in 2027?

Great. Really excellent question. And actually, we're all very excited to see the acquisition of the Terns by Merck with obviously, really good price, $6.7 billion in all cash. I think the positive side is really that means the CML market globally is actually quite big, right? So 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 like lung cancer, breast cancer. But if you look at the history, the first generation, the Imatinib or Gleevec, actually, just in the CML alone, the peak sales before patent expiration is almost $5 billion peak sales annually, right? So I think overall, the current CML market globally, the peak sale is about -- I think the total annual sales is about $7 billion.

And Asciminib last year already reached more than $1 billion sales. So I think there's an estimate the potential just CML global market, the peak sale can reach over $14 billion. So I think this is also supported by the Merck acquisition of Terns primarily for the CML drug, TERN-701. So that's really 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 2 years ago, June 2024. I think globally, Takeda will be our partner. I think as you know, in the CML and AL space globally, Takeda is really one of the leading company aside from the 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 2 drugs, right?

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

Yes. I think we currently push forward really full speed the best effort for the GLORA-4, the high-risk MDS registration trial and also both POLARIS-2 and POLARS-1 for the Olverembatinib. I think the POLARIS-2 or POLARIS-1 -- POLARIS-2 is 6 months rate MMR rate after the last patient for the potential accelerated approval. And POLARIS-1 is 3 months MRD-negative CR rate. So I think once we complete enrollment, those 2 probably most likely would have an opportunity to file the NDA in 2027. The GLORA-4 actually also have a good chance because we enter -- I mean, we enroll patients very fast as in this indication with the Bcl-2 inhibitor, we are the only registrational trial globally for high-risk MDS because many drugs failed, including VERONA trial was inactive.

So we do see a really strong interest and really good enrollment in that space. And with the current protocol achieved, I think this is -- in my 20 years of drug development record, it 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 CLL, we actually did 3 different registrational trial because of different landscape and different regulatory requirement. So I think we are very happy to see the GLORA-4 registrational trial enrollment is actually really promising and we potentially also looking forward to have the NDA filing in 2027.

Your next question comes from the line of Gregory Renza from Truist Securities.

Congrats on the progress. This is Supawat on for Greg.

Just continuing on the theme of the last question. Just I was wondering if you could characterize Olverembatinib's profile relative to TERN-701, particularly around the 24 weeks or 6 months MMR rate with your existing data? And then just as a follow-up, so on -- I know you have a POLARIS-2 study going, but just curious about potentially expanding into second line or earlier lines in CML. What's the progress on that one?

Thank you. Very good question. Obviously, we are very happy to see Tern's acquisition and also 11 data presented at ASH last year. But I think Olverembatinib will really have a unique advantage based on the clinical data, right? So we're probably the same ATP binding inhibitor as 11 and the Tern is more like Asciminib as allosteric inhibitor. But do remember, both drugs are in Phase I or Phase I/II and but they have much less patient number compared to Olverembatinib. And this is based on the current data, they are less than 100. And also the dose in terms of the RP3D or registrational trial has not established for both drugs. And at least 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 Asciminib data require 5x dose for those with T3151 mutation.

So clearly, there's no long-term safety data or efficacy data, and there's no also report on any efficacy in the Ph+ ALL. And specifically, if you look at the -- you mentioned like MMR rate, I think one is much less patient number. But 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 PIs from MD Anderson and others were heavily pretreated. They are representing the CML patients of fourth or fifth line and 1/3 of them has T315I mutation. So I think all the B-cell inhibitor, either kinase inhibitor, allosteric inhibitor, the response is really depend on the patient baseline characteristics and how many prior lines treatment and mutation profile.

So I think that the -- of course, this is not head-to-head comparison. But just with the current data, I think we really demonstrate very broad, very potent activities and also long-term safety profile and efficacy as well. So I think that the -- another thing, I think for both drugs, especially under the Project Optimus, FDA would require Tern's compound and others have to do the RCT, right? They have to do the RCT trial to get approval. And in that case, they also must have a control arm. So it's hard to see what will be the control arm, but these are definitely required based on the Project Optimus, the optimal dose in terms of safety, efficacy and the RCT design and the control arm. So -- but I think overall, we are really confident, especially with our partner, Takeda, we're going to position well for the late line CML for those with mutation and also very active data in the Ph+ ALL. And we are -- we already conducted and published the ASH data for the second line, the CML patients. I think actually, in China, the approval label is what we call the near second-line approval because its 2 TKI resistant and all intolerant. So I think we are really confident we will benefit the patients for those early line as well. But of course, we will conduct the 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. But we know that BeOne has the Bcl-2 inhibitors just approved recently as well. Just curious how that would play into dynamics for Lisa's uptake in 2026.

Yes. I think that the -- first, in China, we were the first domestic Bcl-2 inhibitor commercialized last year. So we were at least 6 months ahead of BeOne Sonrotoclax approval in China. That's number one. Number two, I think based on the data, current data safety and also another thing is the Sonrotoclax dose ramp up is similar to the Venetoclax, weekly dose ramp up and the starting dose for Sonrotoclax is actually 1 milligram. And the approval dose is 320 milligram. So from 1 milligram to 320 milligram and with 5 different dose strengths and taken 9 steps, okay, to do the dose ramp up. I think that's really not convenient for patients with CLL and SLL. And also, if you look at the overall safety profile, the SAE even some of the deaths in that registrational trial and the infection rate and so on, Lisaftoclax is probably the best among the currently 3 marketed Bcl-2 inhibitor. And actually, this on the published drug label, Sonrotoclax actually have even worse DDI risk among the 3 drugs.

So I think 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 and also our GLORA-2 and GLORA-3 also approved by CDE and other countries. The GLORA-2 will offer the patients with CLL, the first-line treatment in combination with acalabrutinib in fixed duration. The 18 months fixed duration with the CIT as a control arm. I think that actually is doing well in terms of enrollment. And the GLORA-3 is the AML. And we are also the first -- the only the AML registrational trial approved by the CDE a year -- more than a year ago and currently active enroll. And 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. And of course, they both are not yet not for the U.S. or Europe because of the control arm or because of the trial design. But I think to answer your question, I think we'll do well, not just because we are 6 months ahead of approval for Sonrotoclax, but based on the very excellent drug properties and the clinical data and as well as the multiple indications, we are more in advanced position than Sonrotoclax in China or globally.

We will take our next question. Your next question comes from the line of Jeet Mukherjee from BTIG.

Two 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?

And 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 I&I or CNS diseases?

Yes. 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. So to cover -- our aim is to cover at least 80% of the sales potential. That represents probably around 2,000 hospitals, okay? And so we already covered about 1,500 hospitals, okay? So the commercial team for the hematology/oncology is really different than like a solid tumor, lung cancer, breast cancer. As those indications probably need easily probably 2,000 to 3,000 sales force to cover the 80% potential sales. So that's the benefit to develop the hematology/oncology product in terms of commercialization in China. So I think we currently have 300 staff in the commercial team. We will continue to make that -- to expand that to about probably 400 to 500. And then 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. The 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 covalent or noncovalent 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. So 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.

Your next question comes from the line of Matthew Biegler from Oppenheimer.

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 questionnaire, like do you think the CLL market is heading in the direction of an all-oral time-limited therapy ala CLL-117 trial that we saw at ASH? And do you think that, that set up -- or how do you think that setup plays to Ascentage favor here with BTK degrader and Lisaftoclax?

Excellent question. I think obviously, the BTK inhibitor is well established for the CLL/SLL globally. And the current inhibitor already generate annual sales more than $14 billion. So that's a huge benefit. But at the same time, as you pointed out, the CLL, especially some of the young patients with the CLL, they don't like to take either BTK or Bcl-2 inhibitor for the lifetime, right? So the fixed duration, especially the combination of the BTK currently mostly inhibitor with the Bcl-2 inhibitor really offer the patient another option. They don't have to take the drug lifetime, right? So the current data pointed out actually at least the combination BTK inhibitor primarily with the inhibitor offer a good benefit in terms of really durable PFS over 5 years, right? And the Bcl-2, our drug Lisaftoclax having 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.

And then on top of that, with the degrader, it's not too late because they take care any of the inhibitors issues, mutation or not. So -- and 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 a long-term benefit in terms of PFS. And then in certain cases, because you offer the best treatment regimen early on, then you may actually offer the clinical cure for some of the CLL patients. That's in the CLL/SLL space.

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

Your next question comes from the line of Christopher Liu from Lucid Capital Markets.

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? Because they have competitive product, ponatinib that's based on the antitrust rules. And there are cases before that in the antitrust issue that they may have to return the drug if there's that competition, the antitrust issue. So the current agreement, but still is exclusive global partnership. So basically, both Takeda and Ascentage are bound to have that partnership to work together. That's number one.

Number two, of course, they have to get either clear antitrust or to wait the patent expiration of ponatinib, which I believe is later this year or early next year. I think that with that patent expiration, then there's no issue in terms of antitrust issue. Thirdly, I think for your question, of course, first of all, we are already a partner. We are strongly bind exclusive. But at the same time, in terms of when to access the option, which I honestly cannot speak for my partner. But with the Merck acquisition of Terns for over $6 billion, I think there's 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 it is a benefit to both parties that we move forward, pushing forward full speed on the Olverembatinib commercialization for the global market.

And 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 that we are really open and flexible. We -- as I mentioned at the JPMorgan conference, we are open, flexible, 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 and the more global market. But of course, at the same time, we are within the time frame of be ready commercialization in 2 years and many of the experts in the commercialization is that you need to be minimal ready 2 years ahead of anticipated commercialization. So I think we are in a position and actively looking for the Chief Commercial Officer.

That's 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 are really working hand-hand in parallel. I think either case we'll benefit strongly our Lisaftoclax commercialization at least in U.S. and also through the potential partners either U.S. or global. So 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.

Your next question comes from the line of Michael King from Rodman & Renshaw.

I had a question about the allosteric inhibitors and that was entered earlier in the call.

So what's the question?

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

Okay. No, I think the current data, first, asciminib as allosteric is doing well, right? Last year, sales more than $1 billion. And in certain countries, like U.S. also received the conditional approval -- I mean, accelerated approval for the first-line CML. So -- but the current compound 11 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. So I think the -- I mean, ponatinib, of course, there's a patent and safety issues. So currently, our strong competitor, to be honest, is considered asciminib. And -- but they are not active in about 40% of late line CML, which require 5x dose or 5x the cost. And all the drugs based on the current data does not show activity or strong activity as Olverembatinib in Ph+ AL.

So I think those 2 are based on the current clinical data, which Olverembatinib has advantage over those asciminib. And 11 Terns first still early, require RCT trial and approval by the FDA. And more importantly, I think the late line, 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 the focus -- if you look at the current market share, 2 of the second line actually is taking the most market shares. Among the 7 billion annual sales, 2 of the second line has been consistently taken each about $2 billion annual sales, okay?

Moving forward, I think currently, there's -- including the asciminib, there are 5 drugs with first-line label. So for Terns or any other compound try to moving into the first line is going to be heavy up hill battle and they also take a long time and very costly. So I think our focus really moving forward and also based on the data is probably Olverembatinib will be the first choice of the TKI for the second-line patients. So in that regard, we don't worry about the competition of the first line. Actually, more first-line treatment, the patient will favor through to Olverembatinib in terms of the best second-line treatment.

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 very timing in terms of our annual report for 2025, representing the first year we are -- have a Dual-Engine for commercialization, build a full-scale functional sales force and also the first time as a dual listed, dual primary listed company on NASDAQ. So 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 best 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 our partners for the global market expansion. So we are very excited with our strong achievement, the milestones transformation year for 2025. And looking forward, we are more excited to see all the registrational trial advance well, looking forward to have -- 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 and looking forward to working with you all and all the investigators and investors around the world to bring the best drug to benefit patients globally. And thank you all. Have a good day. Thank you.

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

Thank you. Thank you all.

Here at the Guggenheim Conference. Here at the Guggenheim Conference. My name is Brad Canino. Happy to be sharing the stage for the next fireside with Ascentage. We've got Veet Misra here. Thank you so much for joining us, Veet.

Thank you for having me.

And maybe we can just kick off if you can give a brief overview of Ascentage and where you are today, core focus of the company, where you've got the footprint and what you see as really the key pillars of the strategy for the company.

Yes. Thank you for the question. So Ascentage is a public company, dual listed on both the NASDAQ and Hong Kong Stock Exchange. We're a global company, close to 800 employees at this point. We're a commercial stage in China with 2 novel products for oncology indications in hematology. And we're rapidly growing.

We have a pipeline of 7 disclosed compounds, including the 2 products I mentioned, each of them novel, best-in-class potential, spanning essentially the big markets in hematology. And we have an internal discovery engine as well.

In terms of the breakdown, the spread of employees, predominantly in China, but we have over 100 in the U.S. So China, it's discovery, innovation, clinical trial execution and sales. In the U.S., clinical trial execution, we have 4 U.S. registration studies ongoing. So the U.S. is going to be our global market hub, which we're going to be -- that's the next chapter of the company to -- in terms of its global expansion commercially.

Okay. So great overview of the company. You've got a decently large pipeline of products as well. Maybe introduce the marketed products and the late-stage pipeline.

Yes, certainly. So in terms of the marketed products, we have, firstly, a third-generation tyrosine kinase inhibitor called Olverembatinib, which is a third-generation TKI in a space that's gotten a lot of attention in recent months.

Essentially, this is a disease category where there's been imatinib in the space brought out by Novartis in 2001. There's been the need, which increased survival significantly, but there's been the need for additional TKIs to be brought to meet patient needs due to resistance. There's the gatekeeper mutation, T315I, which is about 25%, sometimes 30%, depending on the representative population of CML.

And then there is safety concerns that can arise in the near term or later term and intolerance issues. That has been the case of the second-generation TKIs. It's been a large pharma category. There is a worldwide unmet need for CML and also ALL, both in terms of the pediatric population. It's the #1 childhood cancer, including solid tumors and also spans adult and elderly population as well.

So TKIs have to be especially potent to address ALL as well. We're running a U.S. registration and a part of a global registration study in ALL. So we're excited about that. And then also, we have a BCL-2 inhibitor approved in China called Lisaftoclax. It's the second ever BCL-2 inhibitor to get approved ever since Venetoclax got approved by AbbVie in 2016. So it's been a 9-year journey getting that on to the market.

There's a competitor out there that has a BCL-2 inhibitor that got approved for MCL. And essentially, the characteristics of our compound are a daily dose run-up as opposed to weekly. And we also have not experienced with our compound DDI issues, which is a concern as it relates to the importance of combining with other agents, including namely BTK inhibitors.

I'll jump to BTK. We have a BTK protein degrader that we just announced in early January, a U.S. IND clearance for. We subsequently last week announced China CDE clearance. We have an exciting preclinical package of this BTK protein degrader. We believe it's quite differentiating versus our competitors, which we'll talk about more over time. And that yields a combination approach with a BCL-2 inhibitor, which we have obviously in-house.

So we feel like we have the -- the only company that has a third-generation TKI and a BCL-2 inhibitor, both of which we believe has strong best-in-class potential. And to answer your question about the rest of our pipeline, we have 3 multi-kinase inhibitors directed towards solid tumors, a range of solid tumors that we're carrying out.

And we have a discovery engine, as I mentioned. So we also are bringing forward a PRC2 complex inhibitor, which we call APG-5918 for now, directed towards both multiple anemia indications, including SCD, beta-thal and oncology where we've seen some companies recently go after sickle cell and prostate cancer using the same type of approach and have yielded exciting results, but -- and Pfizer has an EZH2 inhibitor, part of the same complex.

So there's really quite minimal number of players in this category as well. So this is kind of our banner approach in terms of commercialization, global clinical execution and bringing about additional novel compounds to bring forward in the pipeline.

Great. Maybe we'll drill into the BCR-ABL first a little bit more. I mean you mentioned in that intro, the mutation potency, the improved tolerability. Maybe give a bit more granular details around that differentiation compared to the marketed products and the clinical stage products that are competitors that are being developed.

Yes, certainly. So it's been interesting to see the attention onto the CML space, especially in the last year, maybe slightly more than a year. There's been a couple of companies. I guess I'd put ourselves in that category that are essentially addressing the unmet need.

Some people can view it as disruptive, maybe in the sense that it's been, as I mentioned, a large pharma category. The issue with the patients is eventual intolerance and resistance to second-generation TKIs. There's a drug Ponatinib by Takeda that's addressed a lot of the concerns of second-generation TKIs.

Unfortunately, it has issues as it relates to toxicity. We do have a relationship with Takeda as a lot of people probably know where they have an option agreement ex China as it relates to Olverembatinib. We believe that in itself is highly validating of our approach as a potential franchise extension strategy for Takeda.

So I think one really needs to focus on potency, efficacy and long-term durability. Our compound got conditional approval and eventually full approval in the NRDL in China starting from 2021. So we have a number of years of history over our competitors that are disrupt trying to be disruptors. I think that really matters.

I think people get caught the excitement of looking at data cuts, looking at the safety efficacy point in time versus the pharma company standard drug and essentially extrapolate from that. That's fine. There's nothing -- one has to, however, take into consideration in the landscape, who are the ones that are showing durability over time because that's what matters when dealing with CML, the name of the game is survival.

So we have now the benefit, especially being a drug that is approved in China, where our KOL IST network and relationships have also done effectively post-marketing studies. So we've done -- so we have -- actually, there's published data now out there in conferences that have shown and very high reputable publications, Nature Journal of Clinical Oncology, et cetera.

Long-term studies, 4-year, 6-year case studies of patients who have had multiple failures of TKIs. Often, they even rotate back to a drug that hasn't worked before. It's because there's limited options. And then you can see patients actually revert back to having MMRs when they have had declines due to resistance.

And in addition, and this is important as well, patients have converted from advanced CML, AP or BP, acute phase or blast phase where the overall survival prognosis becomes more and more poor, back to CP, which is the majority of the CML cases are CP. They're diagnosed most often as CP. But to actually get a very difficult-to-treat population to revert back, that's quite meaningful. So our competitors aren't even close to that point yet.

Also, we have -- since we have the benefit of having both the TKI and the BCL-2 inhibitor, we've actually in-house in one company. We've actually done studies and others have as well as investigators combining our drug with Venetoclax, which we can do with our combination with our proprietary compound and have shown patients can achieve deep MRD, so MRD-negative CR rates. And this is important because these patients can then be eligible for allo-HSCT, which means they can then go on to longer-term potential remission.

So these are the types of studies that are being carried out right now with our drug. And this is what you want to see in terms of the kind of the long-term durability of the drug. DOT equates to sales. That's why I think this has also been a market that's caught the attention of investors again. And we've shown this type of effect in ALL, which is, as I mentioned, a difficult-to-treat disease, unmet need.

Great. Now maybe you can speak a little bit about the POLARIS-2 study for CML. Design for that study, what you're going up against and what you think the bar is for success to make that a drug that is competitive on the global stage?

Yes. I think the design is a nice rational approach to show the safety efficacy profile of our drug versus. In this case, there's 2 parts to it. One is a -- has a control arm, Part A against bosutinib, Pfizer's second-generation TKI.

And then there's a Part B that's a single-arm only T315I mutants. So this study is a global study, including the U.S. and EMA. We are advancing enrollment this year. We look to have majority of the enrollment actually complete this year. So we'll give more guidance as to when the trial is going to be completed, but progressing well.

I would say that one of the things is that we feel like there's a good probability of success given the trial design going against bosutinib. The endpoints are 24-week MMR and then a longer-term 96-week MMR. So it's designed to truly show the go -- the FDA approvable endpoint, and EMA approvable endpoint.

And also will emphasize the potency, hopefully, in T315I. So not to -- given the experience in China and patients, post-marketing studies, as I articulated, there's papers out there, publications, 4-year, 6-year follow-up. We feel like this -- when looking at the totality, this design will get us a good outcome, hopefully. Yes.

Okay. Let's switch a little bit and talk about the BCL-2, Lisa. You have an approved indication in China for that. Maybe discuss that in detail. But then where do you see the vision for this product potentially globally?

Yes. So one thing I should mention though for the POLARIS-2, there's actually a crossover as well between bosutinib and our drug as well. That actually has helped to stimulate enrollment also.

Yes. So to answer your question, so the -- I think one thing to note in terms of the population that was approved in the registration study in China, it was a very deep challenged patient background population. It was a pivotal Phase II study that yielded approval. These patients had complex karyotype, almost half had -- were classified as complex karyotype. 100% of them had BTK exposure.

A majority of that group were actually truly intolerant, resistant to BTK inhibitors. In China, the characterization has to be precise. There is really no one wants to -- one needs to be very intellectually honest with the regulators there. So you can kind of take it at its word that these were truly pretreated resistant BTK inhibitor patients. And with that background, actually, we did get approval with, I think, a label that was better than the market anticipated.

The specific language was patients who have received at least one prior systemic therapy, including BTK inhibitors. And essentially, that language doesn't have the word resistant or refractory in it. So it's -- that allows doctors to prescribe [indiscernible] as a 1.5 line therapy, not a second-line therapy.

We've actually shown at ASH taken forward this patient population have demonstrated high ORRs and overall survival in this patient population, carried it forward. So again, we have the benefit of post-marketing in China that we can carry forward here. And we feel like that with a lot of the noise that was going on, it's still not fully resolved yet with China versus U.S., how much of that is valid.

We've been hearing that from other companies. I think we're more rational about that now and just kind of looking at the data where it is and not discounting so much what's going on in discounting data from China. These are now very extremely well -- and these have been for a while, validated by very strong reputable publications, PIs. So we'll -- and obviously, we're conducting global studies as well with the proper balance representation of patients from each part of the world.

Yes. And you offer a different dosing schedule than Venetoclax as well in terms of the ramp-up and everything. What's been the experience like that? Maybe talk to the Chinese experience, but also this has been used with some global investigators in clinical trials. How do they see that different from Venetoclax? And what's the positive aspect of that? And how is your drug exclusively able to deliver that?

Yes. So the dosing matters. This is a community oncology physician setting compound. So consistency as it relates to -- we've seen some inconsistency from competition as it relates to what is the -- ultimately going to be the multi-week dosing schedule for their drug.

For us, it's clear. We have a 6-day daily dose run-up. So that is important for safety when you think about CLL and SLL and then other indications as well, such as AML, which is obviously has a high mortality rate.

And then obviously, we're going after an area, which is a big opportunity for us, high-risk MDS. There's no other company that's doing a Phase III registration study in this disease category. It's a multibillion market opportunity. And we are conducting a global study in HRMDS.

In addition, the other aspect that's important is DDI, drug-drug interaction, because the combination with the BTK inhibitor or a protein degrader is definitely going to come into -- it's already in play with the inhibitor, but now the big push is for fixed duration therapy. So obviously, you want to have elimination of DDI issues, but we're the only ones who definitively have shown there's no DDI issues with our compound. So that's going to be interesting especially as the BTK protein degrader becomes more and more high profile.

And then when you think about supportive care as well, like antifungals, that's where DDI also comes into play. And then, of course, the other area is bone marrow toxicity. So this has enabled us to really push forward in HRMDS. Venetoclax has shown years prior inability to treat multiple myeloma due to 2 Phase III studies showing bone marrow toxicity.

And then subsequently, as the more details came out last year during SOHO in HRMDS. So -- and as far as we know, another competitor with a BCL-2 inhibitor is not going after HRMDS,'re going after MM. So this is ours, to be frank, with HRMDS, a great opportunity for us. And then one can only go after this type of category with all those characteristics intact.

Yes. So let's talk about MDS for a bit. You've got the GLORA-4 study. Venetoclax did have a study that was unfortunately not successful. What is the rationale for bringing your drug there given it's the same mechanism? Maybe how does the differentiation play into that? And what are the key elements of that trial design that we should be paying attention to?

Yes, it's a really good question. So that VERONA study you're referring to with Venetoclax and HRMDS, the design was VEN Plus, an HMA, Hypomethylating agents, in this case, AZA versus AZA. And it's been -- it was known for quite a while leading up to the actual full disclosure of the results that the trial failed.

And we were embarking on the same design as well, as you mentioned, the GLORA-4 study. It was a little bit like we're on the edge of our seats, and we're getting a lot of questions about like what exactly went wrong in that VERONA study because you're going doing the same design.

Well, then finally came out during SOHO that the design of that trial was a double-blind randomized placebo-controlled study. And what occurred was there was early in the study, a withdrawal of drug in the active arm, early in the study. And in this case, it was AZA because you -- the investigator could only pull back on the known drug. But it essentially confirmed our position all along that it was the toxicity of Venetoclax. The hazard ratio was 0.908. So it wasn't even the near miss.

And unfortunately, the survival curves kind of both converged, both arms at 22 months. So it's, however, validated our approach, and we're really dedicating a lot of our resources to push enrollment.

The other thing about GLORA-4 is we have a dual primary endpoint. So the longer endpoint, of course, of overall survival, but we also have complete response rate as an endpoint -- primary endpoint, which could be the basis for accelerated approval, we'll see depending on the results.

Okay. Great. Maybe in the last minute or so, if you could just talk about across the portfolio over the next 12, 18 months, what are the top catalysts and milestones that investors should be focused on with everything you've got going on?

Yes, exactly. No, for sure, like pushing forward on the registration studies, as I mentioned, POLARIS-2, POLARIS-1, GLORA, we didn't really talk about that, but that's a combination with BTK inhibitors and then GLORA-4, so pushing forward. This will -- is our foray towards commercialization in the U.S.

And then also as it relates to the early-stage pipeline, a lot of attention now brought towards the PRC2 complex, EED inhibitor.

So Phase I results in that as well as the BTK protein degrader, giving more in due course, the differentiation, specific differentiation of that versus our competitors. So we've seen for both those cases with comparables that early small -- really small patient sets, ultimately, you need to have the right number to show safety, efficacy long term to instill confidence.

But you can see how even small number of patient sets can really move the needle in terms of value creation. So we're definitely allocating the appropriate resources for those as well to give the public more data. So that's been our push, and we're essentially well capitalized at this point, and I think have good optionality.

Okay. Great. Well, Veet, thank you so much for sharing the story. Thank you. Thanks, everyone, for listening in.

Thank you, Brad.

Good afternoon, everyone. Thank you so much for joining us for another session at the 44th JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here at the firm. On stage, we have Ascentage Pharma. I'll now pass the mic to the CEO, Dr. Dajun Yang, for a short presentation, followed by a live audience Q&A. Dr. Yang, welcome. The stage is yours.

Thank you. Really honored to be here at the main conference presentation for the first time. And we were supposed to do our presentation last year, but due to the planned IPO immediately after the JPMorgan meeting last year, so we had to cancel our presentation last year.

So it's a great honor to be here. And this year, we have made a lot of progress. And as I said, we did a great IPO last year following the JPMorgan meeting and also led by JPMorgan last year as well.

So this is really the overview of Ascentage. For some of you who may not know us before, let me go through this in a little bit more detail. Ascentage actually founded about 16 years ago, in 2009, and we are really truly global and commercial stage hematology/oncology company. We have 2 novel commercial products targeting BCR-ABL and also Bcl-2. We are one of the few dual listed on NASDAQ and the Hong Kong Stock Exchange. And up to the last financial report, we have $420 million of cash. So that will -- can support our current R&D plans through 2027.

We have a very robust pipeline. We have 7 novel active clinical stage compounds targeting more than 10 indications, with about 30-plus FDA-cleared INDs, and we actually received 17 orphan drug designation by FDA and also by EMA, 4 Fast Track designation, 2 of them are pediatric. We run at the time, more than 40 clinical trials globally. I think one thing really makes Ascentage standing out is that we have global IP protection over 478 global issued patents, about 500-plus more pending applications. We publish regularly on JAMA Oncology, Clinical Cancer Research, among other peer-reviewed journals globally.

Currently, we have close to 800 employees worldwide. Overall, we did or ongoing 13 global registration trials, including 4 FDA-cleared Phase III registration trials. Company is incorporated in Cayman Islands with headquarter in China, Suzhou, Rockville, Maryland and also Sydney. This is actually our headquarter in Suzhou building, the R&D center. So these are 2 novel commercial stage products with global opportunity. Olverembatinib is the third-generation BCR-ABL inhibitor approved in China for CML-CP with or without mutation and about 2 TKI, including the intolerant. And we are running 2 global Phase III studies cleared by FDA and EMA.

On the right, we have Lisaftoclax, the novel orally active selective Bcl-2 inhibitor approved just 6 months ago in China for the CLL and SLL after BTK therapy. I think for this indication, we are actually the first one globally after BTK in CLL with a single agent as Venetoclax was only 17p at deletion indications. We also have 4 global registration trials with 2 cleared by FDA and EMA.

We also have 4 global registrational trials with 2 cleared by FDA and EMA. This is our really the world-class innovative and a highly derisked late-stage pipeline. As you can see, the first 2 are commercial stage, targeting the variety of heme malignancies. We also have 3 other novel compounds potentially the first-in-class, these were successfully developed to the market. Those focus on FAK, focus on MDM2-p53, Bcl-2, Bcl-xl. There's no currently approved product yet globally.

I think there are also 2 exciting programs targeting the PRC2 through the EED, have potential both for oncology anemia. Just about last week, we announced clearance of BTK degrader cleared by FDA for the global study.

Here's a little more information about the Olverembatinib, HQP1351. As you can see, we have this product approved in China since 2021. That's why I said it's highly derisked. We already treated over tens of thousands of patients, CML with and without mutation and also Ph+ ALL. We have 3 global programs, POLARIS-2 targeting the CML with a single agent with the control arm bosutinib cleared by FDA and EMA and also POLARIS-1, first-line Ph+ for ALL patients. This is actually a great result. With the Part A of POLARIS-1 data we presented at ASH just last month, we doubled the 3-month CMR rate over like ponatinib in the same patient population. And we also received breakthrough designation by CD.

We also have one small indication targeting SDH-deficient GIST. This is a monotherapy for pivotal registration trial. And this is a group of patients which has no effective therapy globally. I think really exciting to see is that even that this is a conference where there are at least 2 other peer companies are targeting the same like a CML patient population received great attention at Street.

So overall CML market currently is over $7 billion or $8 billion and asciminib peak sales already increased from $3 billion to $4 billion. And Olverembatinib is strongly positioned for T315 mutation and compound mutations and could be the first choice for the late-line CML globally. There's another indication is the Ph+ ALL. It's very prevalent in Asian countries as China, Japan. Currently, there's no effective, safe small molecule drug and Olverembatinib is a global registration in the first-line Ph+ for ALL.

I think the data so far in the last almost 10 years development in the clinic with the 2 guidance that we entered, NCCN guidelines and also CSCO in China. I think you can see we have a really truly differentiated efficacy profile as a single agent. We show strong -- also really safety profile in Ph+ ALL patients. The longest time patients use our drug is almost 10 years since the Phase I in 2016. And we have a 5-year follow-up for the CML patients after Phase I and also about 6 years follow-up for those in the AP patient population. And we actually had several presentations at ASH last month with strong activity in other rare disease like [ MM ], also FGFR rearrangement, CML, VP, et cetera.

So basically, Olverembatinib demonstrates strong activity, especially in this slide, leading by the Dr. Kantarjian and Dr. Jabbour at MD Anderson. This is actually all U.S. patient population. The initial result already published on the ASH and JAMA Oncology. As you can see in this heavily pretreated, truly failed resistant CML patients, those who failed ponatinib, who failed asciminib and also over 30% of them have [ T31 ] mutation, okay? This is a really different patient population, as you see from some of the peers presentation at ASH or this conference.

So with this heavily pretreated then almost the last line after 4, 5 line patient population, we see a greater efficacy as a single agent. You can see that in those who failed ponatinib or asciminib, will receive a single agent about 40% or 30% MMR rate. There are few patients actually fail both, ponatinib and asciminib. We still see the single-agent benefit.

I think another very exciting data is what we released last month at ASH that in the Ph+ ALL, the newly diagnosed patients, this is part A of our global Phase III trial, the POLARIS-1. As you can see, in this population patients, we can have 64% MRD-negative CR rate, okay? This is almost double the same patient population ponatinib did about 34%. Of course, the control arm, the imatinib only can do about 16%, 17% CMR rate. We also have demonstrated very good safety profile.

Another exciting data is really on the second-line treatment. This is in the CML-CP patients, patients who use either imatinib or one of the second-generation dasatinib or nilotinib and then immediately after the first line using the Olverembatinib. You can see MMR rate is over 40%. And actually, in the patients who in the first line use the second-generation compound do receive even better response.

Another very exciting efficacy data is in this rare MM patient population with FGFR rearrangement. Currently, there's really no effective treatment. And we take quite a few efforts to enroll about 20 patients. And as you can see, they have a really robust activity, including the CMR rate and also a complete response after the transplant.

Another really deep remission is in the blast phase CML patients. I think in the interest of time, I will not go into detail, but I think it is important to note is that the Olverembatinib has really broad and strong activity against almost all forms of the CML. The important data is on the safety. I think over the last couple of years, including actually, I forgot to mention, we entered the partnership under the option agreement with Takeda in about 2024, I think. Takeda is a great partner in CML and ALL globally. I think this is actually a 4-year follow-up of the registration trial we did. One thing I want to mention in China, actually, CD have a very high bar. This patient population, they have to fail all 3 TKI, okay? Majority, almost globally, all the registration trial is after 2 TKI. And this particular study, over 140 patients, majority of them had to fail all 3 TKIs, not just imatinib or dasatinib and also nilotinib in China. Of course, this is looking for the EFS as a great data. And the 4-year follow-up, as you can see, this is the safety profile.

In the hematological AE, this is all grade 3 and above. Actually, over the time, because of the benefit of treatment to clear the cancer cells in bone marrow, those with thrombocytopenia, neutropenia actually reduced. The nonhematologic event are mostly grade 1 or 2. I think this is a great safety with a 4-year follow-up.

Another exciting, I think, notable data is actually combination of Olverembatinib with Bcl-2 in Ph+ ALL. In this case, they use the Venetoclax because that's already approved on the market. Remarkable efficacy in the chemo-free setting. And more importantly, the longest patient follow-up in this particular treatment is over 800 days, okay? Of course, we will continue with the PI, the combination of Olverembatinib with Lisaftoclax now.

These are more details of our APG-2575, Lisaftoclax. Lisaftoclax standing for life-saving [indiscernible] class and briefly always just called Lisa, okay? So as you can see, we have the first pivotal Phase II study with monotherapy in -- in the BTK failed patient population approved in China just about 6 months ago. And we are running 4 global studies, especially GLORA and GLORA-4, all cleared by EMA and FDA and major regulatory agency around the world, including Japan.

I want to bring your attention to that the Bcl-2 selective inhibitor actually have really broad multiple heme malignancies. This is just list of 3 here, the CLL, AML and also the MDS. I think the MDS right now, globally no targeted drug approved by FDA in the last 20 years and it's really truly unmet medical need globally and untapped market.

So our solution to those issues is that Lisaftoclax demonstrate great efficacy, entered the statistical guideline, the first time in China and also granted 5 ODD by FDA, okay? I think the notable efficacy data, I will present more details. But more importantly, I think, differentiate the first Bcl-2 inhibitor on the market in the last 9 years, Venetoclax is really the safety profile, okay? I think in all the clinical trials, over 600, 700 CLL patients and overall near 2,000 patients, we really demonstrate this safety profile over the current or only one on the market in U.S., Venetoclax. We designed from day 1, the patient-friendly daily dosing schedule, okay? And we received approval. Overall have a very low tumor lysis syndrome, some studies with 0. And then more importantly, there's no drug-drug interaction observed.

This is really different than the Venetoclax even have a DDI with ibrutinib. Actually, if you know, they recently just released public data, [indiscernible] even have higher risk DDI over Venetoclax. So I think this is highly convenient for patients and caregivers. I think one of the very exciting important study is this GLORA-4 global trial in the first-line high-risk MDS cleared by FDA and EMA. We all know that VERONA trial had a negative result about -- since reported last July. And of course, that's really unfortunate for patients globally. And we are very fortunate to have Dr. Garcia Manero, the leading PI from MD Anderson and also Dr. Xiaojun Huang to lead this global study. I think you will see the data actually really different than the VERONA trial in terms of Venetoclax versus the combo with AZA.

We demonstrated the data in the U.S. study actually that Lisaftoclax has strong clinical activity in AML, MDS as well as those patients who failed Venetoclax, okay? Especially in the MDS, CML, CMML patients, they -- ORR can be 80%, majority actually is a CR. In the exposed AML/MDS patients, we can also achieve about 31% ORR, okay? I think this really demonstrates truly differentiation and strong activity in AML and high-risk MDS patients. These are all U.S. and Australia studies.

This is the summary of our label in China for the CLL, okay? As you can see, we are the first one, the only one with this daily dose ramp-up design, okay? We have only 3 dose strengths, okay, 5 days combination to the target dose and maintain, okay? I think this is the unique strength and also really convenient for patients with CLL. With a single agent after BTK in CLL, actually, this is the first indication approved globally.

I want to also share with you some of the data. Actually, in this patient population, we did a pivotal Phase II. Again, CD has a high bar. They gave us this pivotal Phase II trial design 4 years ago, but a really high bar. They want -- every single patient at that time had to fail the BTK, okay? At that time, BTK was not very commonly used in terms of first line, right? It took us a while to recruit these 77 patients. But also, you can see the data, these patients are really sick patients, right, in terms of [ TP53 ] mutation, 17p deletion and chromosome -- complex chromosome. And then we demonstrate that we can achieve over 62% ORR and also really meaningful MRD negativity and the PFS as well.

So -- and then they -- currently, they still observed in the PFS and OS. The data also had an oral presentation at ASH last month. The safety is also really good with those patients. But in the interest of time, I will not go through the details already presented at ASH. But more importantly, moving forward, I think, Bcl-2 is really -- can serve as a backbone across major -- many B-cell malignancies. This is also an example, we can do the combination with our own small molecule drug, such as with Olverembatinib or our MDM2-p53 inhibitors, either in AML or DLBCL, okay?

I want to point it out that majority of Bcl-2 inhibitor resistance actually is due to the Mcl overexpression, not due to the mutation, right? So any drug can combine, indirectly reduce -- inhibit Mcl-1 will have a synergistic effect. And we are the only company that has those small molecule drug globally.

We also have many other interesting novel pipeline. This is our BTK degrader, APG-3288. I want to point it out, actually, we moved this product very quickly from this decision to go to the program and from the PCC to the IND clearance in less than 2 years. And actually from the PCC declaration, the IND-enabling study to the IND clearance in about 8 months. And we also have other program like APG-5918. This is the epigenetic therapeutic program targeting the PRC2 via the EED. There's multiple indications in heme malignancies besides lymphoma, myeloma and also solid tumor in prostate cancer and more also additional indication in anemia.

This is the data we presented at ASH last month, preclinical data demonstrated the combination with IMiD in the multiple myeloma. I think one of the benefit of this epigenetic target is really to correct this deregulation and restore the function of other important compound, including those in the prostate cancer. This is one example of the activity in CKD anemia model. In China, we already finished healthy volunteer SAD, MAD, completed about the 3-dose cohort in patients with thalassemia. China doesn't have much sickle cell anemia patients. So that's where we see initially clinical proof of concept in the anemia patients.

The last one is the APG-2449. This is a triple kinase inhibitor targeting both FAK, ALK and ROS1. For the ALK, ROS1, we actually received clearance for Phase III registration trial in China. But I think more exciting is maybe on the FAK as well.

But in terms of non-small cell lung cancer, this particular triple kinase inhibition may also offer the benefit because FAK overexpression is related to the ALK inhibitor resistance. And the last one is a tough target, but we have continued our effort is the MDM2-p53. There are many companies working on that, and we have been also working on that for the last 10 years, including multiple Phase II studies. And currently, we are looking for the path for the registration trial with some really truly clinical unmet medical need in the ACC or some of the pediatric sarcoma patients.

So the last one is we also work a long time is the dual Bcl-2, xL inhibitor. This takes a while to develop in the clinic. I think the other peer drug, navitoclax actually stopped all the studies due to some of the target toxicity in the platelets. We solved this problem preclinically by making the prodrug, but still need more study in terms of regulatory path to the NDA. So in the interest of time, I will not go to that much detail.

I think finally, this is a very exciting time to summarize our achievement last year. I think 2025 has been tremendous important year for Ascentage. We achieved the first goal being listed on NASDAQ and also get NDA approval for the Bcl-2 selective inhibitor, Lisaftoclax and also received 2 important clearance from FDA and EMA because these 2 trials are the first-line patients. And for MDS, we are globally the only Phase III studies for the MDS patients, and we are really moving fast on the GLORA-4 enrollment. And POLARIS-1 again, is Ph+ for ALL patients for the first line. And of course, we do everything we can to advance enrollment all these POLARIS and the GLORA registration trial studies.

I think thanks to my team, we work very hard behind the scene. As I'm presenting here, all the major achievements come from our team's effort. Looking forward to the 2026, I think the first and most important one is focus on execution, complete the enrollment for all the registration studies. And also, of course, we will have a continued growth and reach out to more patients in our commercialization effort. And we're looking for the NRDL coverage for Lisaftoclax and advance our BTK protein degrader and also the EED inhibitor in oncology and also anemia, both U.S. and China. I think there's a lot of excitement to come from Ascentage team this year.

And finally, I think I want to enter this slide that from day 1, we focus on the patient, focus on the global market. Right now, actually, you can see there's one missing we have 7, what we call 7 magnificent small molecule drug with 2 already late stage. One day, one of the analysts told me we should refer us as a super late stage. So we have 2 super late-stage global opportunity products. And actually, with the BTK degrader, we're going to target all major 3 lineages of heme malignancies from the CML, ALL, CLL, AML, MDS, multiple myeloma, DLBCL and also anemia.

I think more importantly, we are probably the only company have this chemo-free oral active small molecule drug can do the combination, right? So the combination of our Bcl-2, Olverembatinib, BTK degrader plus other one like EED inhibitor and the MDM2-p53, we are probably the only company who will be able to have this novel single-agent compound and also combination to help the patients globally. Finally, I thank you all for attending, and I'd be happy to answer the questions. Thank you.

Thank you, Dr. Yang. Thank you so much for joining us. Welcome. Let's start the Q&A. For those who are in the audience, if you have any questions, feel free to raise your hand. And for those joining us virtually, you can also submit questions on the portal.

Dr. Yang, first time on the main track at the conference, so welcome. Ascentage had been such a strong performer last year out of the NASDAQ IPO. How do you think about where you stand today from a strategic standpoint? I think part of the observation that we see is that U.S. investors haven't gotten to fully know the story, right? So how do you think about getting traction with investors? How do you think about maintaining your strong position also from a liquidity standpoint as well?

Thank you, Brian. Really good question. Okay. So that's a very important question. First, I think by listing on NASDAQ, we really have the opportunity in the last year to participate in many meetings and the calls, presentations with investors and analysts in U.S. and European countries. But I think more importantly, we will be F-3 eligible next month. We will do everything we can to attract the investors in U.S. and European countries through like ATM, many other approaches. I think that's very important to be able to have more participation, communication, interaction with investors and also have the ways for them to purchase Ascentage stock.

Great. Well, let's start off with something new. I think we've done a lot of work in the past on Olverembatinib and Lisaftoclax. Last week, you announced that there is an IND clearance for a BTK degrader by the FDA. How much can you tell us about the program? Can you talk about just a big picture, how does that fit in, especially now that you have late-stage Olverembatinib and also Lisaftoclax in the pivotal studies?

Great question. I think the BTK degrader first demonstrated our R&D capabilities. We entered -- designed that program and then getting the PTC in less than a year. And from PTC to getting the -- filing the IND about 7, 8 months and received the IND clearance within 30 days through the FDA. And we're looking for -- this is public information that CD already put on the website, starting the clock. Nowadays, CD can be getting IND cleared by 14 days, 14 working days.

I think this is the first time for us to getting the true novel degrader into the clinic. But more importantly, I think with the BTK degrader, first, in terms of clinical program, they will take care of all these inhibitors covalent, non-covalent or mutation or not. That's very important, right? Second, this will allow us to have a combination with our Bcl-2 inhibitors, especially. And also, more importantly, we will demonstrate probably more potential moving forward in the lymphoma. So always using this as the analogy of having Army, the Navy and the Air Force working together to target 3 lineages of heme malignancies, lymphoid, myeloid and lymphoma. And then we have all these 3 orally active targeted small molecule drugs.

That's a Chinese saying. Maybe just go back to the Phase I setup for this BTK degrader. How should we think about this Phase I -- how much can you tell about the dose escalation of the Phase I? And I guess, let's say, down the line a year from where we stand, what should we be focusing on from the first Phase I data cut?

I think the first one -- I mean, Phase I is a typical dose escalation, safety, PK and potentially some efficacy. I think in this case, one benefit for especially our team being able to work both the U.S. and China with the FDA and the CD clearance. This is really truly the first Phase I global protocol, okay? It's one protocol cleared by FDA and the CD, so we can enroll the patients simultaneously. Don't need to repeat, right, the dose part. I think the second, of course, the Phase I typically is all-comers, but we will try to enroll more those potentially benefit with a single agent as well, some of the lymphomas, the CLL. But then we will really move quickly either monotherapy for a certain indication, registration trial or very quickly into the combination with our Bcl-2 inhibitor.

Okay. Maybe just quickly on turning into commercial preparation for the U.S. You have multiple global -- studies are ongoing across Olverembatinib and Lisaftoclax. I mean, I think the commercial question is really leaning on more towards the Lisaftoclax compound, right? So where do you stand in terms of preparation for a commercial launch here? What is currently in place? And how do you think about your 2026 and 2027 as you kind of approach that commercial milestone?

Great question. I think 2026 and 2027 will be a turning point for Ascentage to be the global commercial stage company. I think with the 4 registration trials ongoing, some of them, we're looking for the NDA filing in 2027. The first one, Olverembatinib, our commercialization will be helped by our partner, Takeda. The second one, Lisaftoclax, I was told by many experts in the commercialization says you need to be at least minimum 24 months in advance to be ready, right? So I think we are actually in the effort to looking for the Head of Commercialization, CCO in U.S. And then hopefully, we can bring up the team, be ready for commercialization in U.S. next year. But of course, at the same time, we are open, flexible and willing to sell, to partner.

And just turning to -- any questions from the audience? And just turning to the broader portfolio. You have 7 assets in the clinic, 2 approved products in China. How do you think about prioritizing? I know that there's a lot of excitement around BTK degrader. Is that where you think investors should focus on? I guess this question is more of who is your favorite child? How do you think about prioritizing and where we should do more work on?

Great question. I think, first, we are financially strong. Our budget -- our CFO and the Head of Finance are here. We have sufficient funding to support all the R&D programs through 2027. Of course, we do need to prioritize. We cannot do everything at the same time. But I think the 2 things will be that the -- for registration trial, okay, especially to the first line and relatively quick readout in terms of the primary endpoint, that's where we need to focus. That's why I always tell the team this year is the focus on execution, right, the enrollment, enrollment, enrollment.

Second is to be ready for the NDA filing and commercialization, right? We don't want to be late, right? At the same time, we also want to bring the BTK degrader forward, the EED or PRC2 inhibitor in both anemia and oncology. But at the same time, we are open for all the potential partnership, not just the late-stage program, but also those exciting new targets. As you can see from both the ASH presentation and this conference, there are several peers who are doing quite well with their Phase I data.

Great. Well, thank you so much for your time today. This has been great and congrats on all the progress.

Thank you.