ASCENTAGE PHARMA GROUP INTERNATIONAL (AAPG) Q2 2026 Earnings Report, Transcript and Summary

Hello, and welcome to the 2026 Interim Financial Results. [Operator Instructions] As a reminder, this conference is being recorded. If you have any objections, please disconnect at this time. With that, I would like to turn the call over to Sumedh Neni. You may begin.

Thank you, operator, and good morning, everyone. Thank you for joining today. Welcome to Ascentage Pharma's 2026 Interim Results and Business Update Call. I'm Sumedh Sunkaraneni, Director of Investor Relations and Corporate Strategy at Ascentage. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions. These statements involve risks and uncertainties, and actual results may differ materially. For a discussion of these risks, please refer to our disclosures. Joining me today are Dr. Dajun Yang, our Chairman and Chief Executive Officer; Dr. Faical 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. Faical 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 2 approved products and the late-stage pipeline that's highly derisked. Olverembatinib, our third-generation BCR-ABL inhibitor have been approved, CML-CP in China since 2021. Tens of thousand patients have been treated to date. The longest 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 up. 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 Bcl-2 inhibitors. It also has FDA and EMA cleared global registration trials, GLORA and GLORA-4. Behind those 2, 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/ALK/ROS1 and MDM2-p53 inhibitor, APG-115 and also targeting both Bcl-2 and xL APG-1252 and EED inhibitor 5918 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 2 areas that determine whether franchise reaches patients outside China, global business development and commercialization. I'm really pleased to welcome Dr. Faical 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. Faical, 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 then also was involved in venture investing across leading pharmaceutical industry. And I was in, as you see in the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen as well as midsized biotech like Kadmon and IO Biotech. I was also instrumental in the deal or the M&A that happened between Kadmon and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executed teams at IO Biotech and Ipsen. And when I was at Eli Lilly, I advanced Erbitux and Cyramza as a lead oncology products or antibodies and co-initiated the Pfizer Centers of Therapeutic Innovation. So I'm very, very pleased to join this very, very good team at Ascentage, and I'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 2 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, 2 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. A lisaftoclax was approved in July last year for the treatment of adult patients with CLL/SLL, who have previously received at least 1 systemic therapy, including BTK inhibitors. Actually, we conducted a 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 AZA versus AZA alone. This has been cleared by FDA, EMA, China CDE and also PMDA close to 20 countries. Let me also highlight a few key differentiation versus 2 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 reached the target dose 600 milligram and continue. As you can see, the venetoclax was first approved about 10 years ago, has a 5-week dose run up. The other one just approved Sonrotoclax early this year with a 5-week dosing, I mean, the weekly dosing up by the line dose cohorts, okay? Because Sonrotoclax started with 1 milligram. Initially in the trials, it was 9 weeks. I think they combined 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 very 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 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 SAE incidence, lisaftoclax is also much lower, and no drug-related death reported to date. And in the PK Variability, I think the other 2 are strong, the only 3 or 4 inhibitors, and we show minimal fluctuation in plasma penetration compared to the other 2. I think that the -- also the low dose adjustment required compared to the other 2 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 2 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 2 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 indication of clinical activity, including patients previously exposed to venetoclax. Let's also look at the AML case. The overall CR/CRi rate was 72% with a 61% MRD negative rate. Response was 100% with patients with NPM1 mutation and 83% in the IDH2 mutation. I think it is important, all those trials are actually with patients in U.S. and Australia. This is not the 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 MCL-1 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 BCR-ABL 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 the 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 2 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+ ALL. So POLARIS-1 is also important. This is our global Phase III study in newly diagnosed Ph+ ALL. Again, both cleared by FDA, EMA and CDE and also with breakthrough therapy designation in China. We have already shown strong Part A data at ASH as oral presentation last year, and we continue to advance the global study. Let's look at some of the important bridging study led by Dr. Eli Jabu at MD Anderson. This actually was conducted 4, 5 years ago. And Dr. Eli Jabu, as you know, is a leading investigator in CML and also Ph+ ALL. 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 T315I 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 no other options, but single-agent olverembatinib have pretty good efficacy. I think that this treatment, again, strengths 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 very 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. Let's also turn -- Let's turn into Slide 17. I think that the benchmark is important because then 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 2 drugs TERN-701 and ELVN-001 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 in the first line of the Phase I trial. And we also have -- we are the only ones to have controlled the comparative data set, okay? Those are new requirements from FDA in terms of Project 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 2 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 the POLARIS-1 with low-intensity chemotherapy in frontline. I think that the POLARIS-1, three key important differentiation, the data. One, this is frontline newly diagnosed Ph+ ALL. In most of cases around the world, chemotherapy is still required because of the aggressiveness nature of the Ph+ 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 63%. This is almost double the ponatinib in the same patient population, the PhALLCON 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. Eli Jabu from MD Anderson, demonstrate that if combined with blinatumomab, we can achieve 80% MRD-negative rate and 91% CR/CRi. We also demonstrate importantly, in the Pediatric R/R Ph+ ALL patients. Actually, those data have been available reported first time 2 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 a key because this is 2 orally active agent chemo-free in the Pediatric ALL setting. Moving on to the APG-115, another asset in our portfolio, small molecule targeting MDM2-p53. It actually holds 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-p53 as p53 is one of the most important tumor-suppressor gene. But I think you do see some recent progress that Ipsen achieved -- acquired Kartos' 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-p53 inhibitor combined with the JAK inhibitor in that actually trial as an add-on strategy. I think that, 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-115 in combination with lisaftoclax 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 already 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 lisaftoclax combinability with 3 other targeted small agents all are orally active. I think that the -- we all know, as I mentioned, that the major -- the main reason for Bcl-2 resistance is the upregulation of MCL-1. So we have demonstrated olverembatinib actually can indirectly downregulate MCL-1. We not only have preclinical data, but now have clinical data to demonstrate that combination of the olverembatinib with lisaftoclax can show the synergy, more importantly, not just the CML or Ph+ ALL, but the patients with AML or MDS and the Ph-neg. ALL, 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+ ALL. And again, with MDM2-p53 inhibitor, APG-115, now we have clinical data to demonstrate the safety efficacy, especially in those hard-to-treat soft tissue sarcoma patients. And we are also moving into the DLBCL, AML and MF. Part of the MOA for this combination is the synthetic lethality. Again, we are the only company worldwide have all 3 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 (sic) [ comprising ] 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 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 that with the overall R&D highlights and 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 these 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-up.

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-BTK R/R 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 sonrotoclax in terms of the only approved daily dosing up 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 all important favorable factors for the NRDL consideration. I think currently, as update, we have passed the initial review. We are on the final product list for the NRDL expert review right now. This year, the time line is actually a little bit ahead of previous time line as currently, the -- both the -- there are 2 groups, NRDL experts, officials and those of the health economics experts are conducting the meetings, reviews right now. So we may call 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. They 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 the reimbursement, but the ticket to enter the hospital. Majority of hospital in China rely on the NRDL approval to enter the hospital in terms of prescription. And in case of CLL/SLL, this is chronic dosing patients, reimbursement by NRDL means they can reduce their out-of-pocket payment by 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. Zhai?

Sorry, Brian. So regarding GLORA-4 study, right? Sorry, I addressed somebody else's question. So could you repeat the question?

No problem. Yes, no, I'm just curious how the enrollment is going in the global studies like POLARIS-1 and also the GLORA studies 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 tried to complete their 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 particular attention to that global registrational trial. Regarding GLORA-2, GLORA-3 and Dr. Dajun actually already announced yesterday, we already completed 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 the enrollment for the GLORA-2, which is a frontline CLL/SLL setting combination with azacitidine and with fixed duration. And of course, that one is not with the FDA because the control arm is the chemo-immunotherapy 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 to 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 to share. One is, this is the front line, okay? The frontline patient with high-risk MDS. In the trial design, similar to the VERONA, the combo with AZA versus AZA alone. And this has been cleared by FDA, EMA, PMDA and China. And globally, not because VERONA failed, but also another Bcl-2 inhibitor venetoclax 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 remains globally unmet medical need. And enrollment is doing well because experts around the world in MDS are really enthusiastic, all want to help patients with high-risk MDS. So overall, I think to summarize, we anticipate, as we said before, the enrollment for GLORA-4 and POLARIS-1, POLARIS-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 Nurix or B1 that have more -- better selectivity and stronger efficacy. But that's, again, it 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 really active. Some more so 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 to combine 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 a 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 addressed 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 that I'll just 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 MMR 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 these 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'll 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 is 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 that 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 the 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 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 ALL 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 exercises. 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 Gene 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 they -- 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, is to cover 80% of the market potential with 2 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 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 highlighted 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 T315I mutation and also the compound mutation. Because in the BCR-ABL gene, the mutation not just happened in one hotspot. The T315I is considered a gatekeeper mutation, differentiate those in terms of third-generation BCR-ABL inhibitor. But on top of that, there's also more than one mutation called the compound mutation in the same cell, okay? And currently, asciminib and also those TERNs or ELVN 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 occurs 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 T315I 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 ELVN or TERN-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, 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 III trials for the registration. So that's why we have to conduct the RCT. We have to have the control arm like bosutinib. 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 BCR-ABL inhibitor to a patient who failed after first line early, right? You don't want to wait until 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 of 4.5. So patients who can achieve a deeper 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 failed the frontline. It doesn't matter it's a TKI or asciminib 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, can you just comment about how that's perhaps changed since sonoro has entered the market? Are these 2 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 5-day ramp-up, as you've mentioned, how that's perhaps translating into more measurable real-world advantages in China.

Okay. Great question. So overall, Bcl-2 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 venetoclax and that daily dosing up was a key differentiation in the beginning. We are the only one approved to go to the clinical trial and approve the label with the clinical data. I think in the CLL/SLL patients, some of the early risk was in the tumor lysis syndrome. That's why venetoclax and also sonrotoclax went to this weekly dosing up, 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 sonrotoclax now, the differentiation in the chronic dosing patients like CLL is actually the safety, right? If the drug tolerated well with less tumor lysis syndrome, less bone marrow toxicity, primarily in our case is we have a shorter T1/2 that translate into better safety profile, less neutropenia, thrombocytopenia and also much less infection. Some of the hematology malignant patients in the clinic presented the 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, right? 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 multiple myeloma, the combination with antifungal drug is essential for those patients. I think the key differentiation, as we alluded to before, is less is more. So they compare -- even with sonrotoclax now on the market, you see from the label that they even have a higher risk of DDI than venetoclax, okay? So I think the differentiation in terms of daily dosing up convenience, better safety profile, tolerance and lower risk of DDI is important for these chronic dosing leukemia patients. I think 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 2 commercial assets and which ones you're perhaps most excited about?

To be honest, it's hard to say which one, it's all data-driven, right? But to your question, we are really happy to see we demonstrate clinical benefit in the pediatric soft tissue tumor setting, combined with, in our case, Bcl-2 inhibitor, right? So one of the challenges for the MDM2-p53 target, that's why currently no approved product yet is this negative feedback loop and also the requirement of 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, the clinical benefit and the MOA of synthetic lethality. On the other hand, even though from the competitive product, the Kartos compound also entered the Phase III registration trial with the add-on strategy of a JAK inhibitor in MF. And obviously, it's encouraging to see Ipsen enter the acquisition with potentially $1.75 billion. I think there is a potential maybe at the end of the tunnel, see that finally MDM2-p53 inhibitor may enter the market or registration path. For your question, I think among the pipeline, we have 5 of them right now. Each one of them have a unique different strength differentiation based on the current data. Obviously, the 2 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 that they currently, in addition to the 2 approved product in China, globally for registration trial, clearly the focus, right? We want to getting the first NDA filed with the FDA on those 2 products. But as you can see in the 5 clinical stage assets, 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 very exciting data and a 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 lisaftoclax. I think you were talking about ven-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 TLS 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.

Great question. Yes. Based on our preclinical data, we have reported using lisaftoclax in combination with olverembatinib able to overcome venetoclax resistance, which we have previously reported at the AACR. We also use very preliminary data we submit to this year ASH. And when the data mature, we have data demonstrated the combo able to overcome the venetoclax resistance. The data is preliminary, but very exciting. We submit the abstract to ASH. So that's just your question. We in the process globally, including in China or outside China in U.S., and we try our best effort try to enroll more venetoclax treatment failed patient population using different strategy based on the known resistant mechanism to target this ven-resistant AML population, either using the combo or our other compound, APG-1252. To address your question 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 (sic) [ endpoint ], we were able to submit the NDA and using the CRi as the primary endpoint and then continue to mature the OS data sometime next year.

I appreciate the detail. And then 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've powered the study for. And I was also curious because your MMR rates grow over time, 48, 96 weeks, how are you handling crossover from control arm ponatinib there? Are they -- 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 tried again to request the FDA finally give the green light, allow those patients who failed from the control arm and 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 allow the crossover, okay? And remember, the POLARIS-2 also have the arm B, mutation with T31 (sic) [ T315I ] mutation patient only that we can do the single-arm design with 48 patients, okay? So I think the total POLARIS-2 is 333 patients and enrolled 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, Veet on your OpEx trajectory and if you're getting to peak -- I know you have a lot of registration studies. Just maybe comment on where we are with the R&D spend and 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 would discuss 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, oh, go ahead, Dr. Yang and then I can...

No, no. Veet, you 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, maximal flexibility and optionality in terms of various alternatives to raising capital. Obviously, when it comes to commercialization, that requires expansion capital. And we believe as a company, we'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 9 registration trial and 4 global cleared by FDA and EMA, majority of these 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 growth revenue with 2 product sales in China. I think we're 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, position 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 really excellent 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.