Q2 2026 Ascentage Pharma Group International Earnings Call

Yifan Zhai: We cannot hear anyone.

Speaker #1: We cannot hear anyone.

Dajun Yang: Hello? Can you hear me?

Speaker #2: Hello? Can you hear me?

Speaker #3: Hello, and welcome to the 2026 Interim Financial Results. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question-and-answer session.

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

Speaker #3: Also, as a reminder, this conference is being recorded. If you have any objections, please disconnect at this time. With that, I would like to turn the call over to Sumedh Neni.

Speaker #3: You may begin.

Speaker #2: 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 Sankaraneni, Director of Investor Relations and Corporate Strategy at Ascentage.

Sumedh Sunkaraneni: 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 am 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 30 June 2026.

Speaker #2: 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.

Speaker #2: For discussion of these risks, please refer to our disclosures. Joining me today are Dr. Gajan Yank, our Chairman and Chief Executive Officer; Dr. Faisal Miarra, our Chief Business Officer; Mr. Jim Ziegler, our Chief Commercial Officer; Dr. Ithan Zai, our Chief Medical Officer; and Dr. Veet Misra, our Chief Financial Officer.

Speaker #2: Yesterday, we issued a press release with our unaudited financial results for the 6-month ending June 30, 2026. That release and the slide presentation accompanying this call are available in the investor relations section of our website.

Sumedh Sunkaraneni: 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. Tsai will also join us for part of the Q&A session. We will then open the line for your questions. I would now like to turn the call over to our CEO, Dr. Dajun Yang. Dr. Yang, you may begin.

Speaker #2: Turning to our agenda, Dr. Yang will open with a business update, and we will hear briefly from Dr. Miara and Mr. Ziegler on the business development and commercial priorities behind our global hematology franchise.

Speaker #2: Dr. Yang will then cover our R&D highlights, and Dr. Misra will review the financials. Dr. Zai will also join us for part of the Q&A session.

Speaker #2: We will then open the line for your questions. I'd now like to turn the call over to our CEO, Dr. Gajan Yang. Dr. Yang, you may begin.

Speaker #4: 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.

Dajun Yang: Thank you, Samet, and thank you all for joining us. The H1 of 2026 advanced a single objective, building Ascentage into a leading global, fully integrated hematology oncology company. We are a company that discovers, develops, conducts global clinical trials, and now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide. We are currently advancing nine global registration trials, four of which are cleared by both the FDA and the EMA. The total revenue grew to USD 44.5 million, up 29% year over year, of which were product sales of USD 41.6 million on a constant exchange rate basis. We are reaffirming cash runway through the end of 2027. Importantly, and playing a role to achieving our global strategic objectives, we strengthened our leadership with the appointments of Dr. Faiçal Miyara as Chief Business Officer and Mr. Jim Ziegler as Chief Commercial Officer.

Speaker #4: We are a company that discovers, develops, conducts global clinical trials, and is now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide. We are currently advancing nine global registrational trials, four of which are cleared by both the FDA and the EMA.

Speaker #4: The total revenue grew to $44.5 million, up 29% year over year, of which product sales were $41.6 million, on a constant exchange rate basis.

Speaker #4: And we are reaffirming cash runway through the end of 2027. Importantly, and playing a role in achieving our global strategic objectives, we strengthened our leadership with the appointments of Dr. Faisal as Chief Business Officer and Mr. Jim Ziegler as Chief Commercial Officer. Both are with us today and will be sharing preliminary thoughts.

Dajun Yang: Both are with us today and will be sharing preliminary thoughts. Let us look at the next slide. This slide, we have two approved products and a late-stage pipeline that is highly de-risked. Olverembatinib, our third-generation BCR-ABL inhibitor, has been approved CML CP in China since 2021. Tens of thousands patients have been treated today. The longest patient on our drug has been near almost 10 years now. We have real-world long-term safety and efficacy data that really few companies at our stage can point to. We also have global registration trials, including FDA and EMA clear, that are 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.

Speaker #4: So let's look at the next slide. On this slide, we have two approved products. And the late-stage pipeline, that's highly de-risked. Over and above TINIP, our third-generation BCI-ABL inhibitor, has been approved for CML-CP in China since 2021.

Speaker #4: Tens of thousands of patients have been treated to date; the longest patient on our drug has been on it for nearly 10 years now. We have real-world, long-term safety and efficacy data that companies and our stage can really point to.

Speaker #4: We also have global registration trials ongoing, including those that are FDA- and EMA-cleared. Our plan is to commercialize above and beyond TINIP in the United States and the major pharma markets.

Speaker #4: The Silver class, our selective BCL-2 inhibitor, is approved as a single agent in post-BDK CRL SAL. Globally, we are the second selective BCL-2 inhibitor to reach the market after decades have passed.

Speaker #4: However, in the single-agent post-BDK CRL, we are actually the first to get approved to the market. The Silver class has a unique daily dose range up.

Dajun Yang: However, in the single agent post-BTK CLL, we are actually the first to get approved to the market. Lisaftoclax has a unique daily dose turn up. We are the only one approved with that label. Enhanced 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 two, we also have five additional clinical stage assets all conducting trials in US and China and the rest of world. APG-2449 is a triple kinase inhibitor covering FAK, ALK, ROS1. The MDM2 inhibitor, APG-115, and also targeting both BCL-2 and BCL-xL, APG-1252, and EED inhibitor APG-5918, and also the newer one joining this year to the US and China phase I trial is the APG-3288 BTK degrader.

Speaker #4: We are the only one approved with that label. Enhanced safety and drug-drug interaction observed today are much reduced compared to other BCL-2 inhibitors.

Speaker #4: It also has FDA- and EMA-cleared global registration trials, GLORA and GLORA-4. Behind those two, we also have five additional clinical-stage assets that are conducting trials in the US, China, and the rest of the world.

Speaker #4: APG-2449 is a triple kinase inhibitor covering FAK, ALK, and ROS1. The MDR253 inhibitor is APG-115, which also targets both BCL2 and XL; APG-1252. The EED inhibitor is 591A, and also, the newer one joining this year in the US and China Phase 1 trial is the APG-3288 BDK degrader.

Speaker #4: In light of our mission to build Ascentage into a leading global hematology-oncology company, we have strengthened our leadership team in the two areas that determine whether our franchise reaches patients outside China: global business development and commercialization.

Dajun Yang: In light of our mission to build Ascentage into a leading global hematology oncology company, we have strengthened our leadership team in the two areas that determine whether a franchise reaches patients outside China, global business development and commercialization. I am 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 attracted them to Ascentage. Faiçal, let me turn it over to you.

Speaker #4: I'm really pleased to welcome Dr. Faisal Miarra as our Chief Business Officer and Mr. Jim Ziegler as our Chief Commercial Officer. Both bring deep experience directly relevant to the next stage of Ascentage's growth.

Speaker #4: I would like to give each of them a moment to introduce themselves and share what attracted them to Ascentage. Faisal, let me turn it over to you.

Speaker #5: Thank you, Dr. Yang. My name is Faisal Miarra. I'm the current Global Chief Business Officer at Ascentage. I have over 20 years in oncology business development, search and evaluation, and I have also been involved in venture investing across leading companies in the pharmaceutical industry.

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

Speaker #5: I was in, as you see at the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen, as well as mid-sized biotech like Ketamine and IO Biotech.

Speaker #5: I was also instrumental in the deal, or the M&A, that happened between Ketamine and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executive teams at IO Biotech and Ipsen, and when I was at Eli Lilly, I advanced arbitrage concerns as a lead oncology product or antibodies and co-initiated the Pfizer Center of Therapeutic Innovation.

Speaker #5: So, I'm very, very pleased to join this very, very good team at Ascentage, and then we'll talk about our pipeline. It's very, very outstanding. With that, I'll leave it to Jim to give you some information on the Chief Commercial Officer.

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

Speaker #4: Thank you, Faisal, 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.

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

Speaker #4: 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.

Speaker #4: My immediate focus is on building the foundation for potential commercialization of our products, including commercial strategy, market access, and the associated capabilities we will need as our registrational programs advance in the United States and other key markets.

Speaker #4: 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.

Dajun Yang: 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 anchor it, and everything behind them is designed to add to our best-in-class portfolio. Turning first to lisaftoclax, our cornerstone asset. Lisaftoclax was approved in July last year for the treatment of adult patients with CLL/SLL who have previously received at least one system therapy, including BTK inhibitors. Actually, we conducted registration trial for the patients who have failed BTK inhibitors. For that indication, we are actually global first one. More importantly, we are running four global registration trials, two of them cleared by FDA and EMA, each of them will have a transformative therapy globally. I think the most important one among the four registration trials for the global strategy is the GLORA-4.

Speaker #4: Our development strategy is the engine for our full global commercialization strategy. Two approved hematology assets are anchored, and everything behind them is designed to add to our best-in-class portfolio.

Speaker #4: Turning first to the Silver Class, our cornerstone asset. The Silver Class was approved in July last year for the treatment of adult patients with CLL/SLL who have previously received at least one cytotherapy, including BTK inhibitors.

Speaker #4: Actually, we conducted a registration trial for patients who have failed BDK inhibitors. So for that indication, we are actually the first globally. But more importantly, we are running four global registration trials; two of them have been cleared by both the FDA and EMA.

Speaker #4: Which of each of them will have transformative therapy globally? I think the most important one among the four registration trials for the global strategy is the GLORA-4.

Speaker #4: In the frontline, high-risk MDS, evaluate the Silver class in combination with azacitidine versus azacitidine alone. This has been cleared by the FDA, EMA, China CDE, and also PMDA, in close to 20 countries.

Dajun Yang: In the frontline, high-risk MDS evaluates lisaftoclax in combination with azacitidine versus azacitidine alone. This has been cleared by FDA, EMA, China CDE, and also PMDA in close to 20 countries. Let me also highlight a few key differentiation with two other currently on the market BCL-2 inhibitors. As you can see, lisaftoclax was the only one designed with daily dosing up in the beginning, and the only one approved with only three dose strengths and five daily dose ramp-up plan, and then reach the target dose, 600 milligram, and continue. As you can see, venetoclax was first approved about 10 years ago. It has a five-week dose ramp-up. The other one just approved, sonrotoclax, early this year, with a five-week dosing. I mean, the weekly dosing up by the nine dose cohorts, okay? Because sonrotoclax start with 1 milligram. Initially in the trials, it was nine weeks.

Speaker #4: Let me also highlight a few key differentiations with two other currently on-the-market BCI2 inhibitors. As you can see, the Silver class was the only one designed with daily dosing from the beginning.

Speaker #4: And the only one approved was only three dose strengths and five daily dosing ups planned, and then reached the target dose of 600 milligrams and continued.

Speaker #4: As you can see, the vanilla class was first approved about 10 years ago and has a five-week dose run-up. The other one, just approved—the renal class—early this year, also has five-week dosing. I mean, the daily, weekly dosing is outlined by the line dose cohorts, okay, because the certain class started with one milligram initially in the trials. It was nine weeks—I think they combined two into one week—so each week they have to do the run-up two times, and then a total of nine dose levels to reach the target dose.

Dajun Yang: I think they combined two into 1 week. So, each week, they do the ramp-up two times, and then total nine dose levels to reach the target dose. I think that's very important for the patients with the CLL/SLL, the convenience, and also reduce the time of hospitalization. Let's also look at the summary of favorable safety profiles and the better drug combinability. We try to compare in the same setting, same patient population, but also be clear, this is not head-to-head comparison. But if we look at the overall, the safety profile in terms of infection and the PK variabilities, lisaftoclax is probably the best one among the three. If we look at the SAE instance, this overall is also much lower and no drug-related deaths reported to date.

Speaker #4: I think that's really important for the patients with CRL-SAL—the convenience, and also reducing the time of hospitalization. Let's also look at the summary of favorable safety profiles and better drug compatibility.

Speaker #4: We try to compare in the same setting, same patient population, but also be clear this is not a head-to-head comparison. But if we look at the overall, the safety profile in terms of infection and the PK variabilities, the silver class is probably the best one among the three.

Speaker #4: If we look at the ACE instance, the Silver class is also much lower, and no drug-related deaths were reported today. And in the TK variability, I think that we, you know, the other two are strong.

Dajun Yang: In the TK variability, I think that the other two are strong, the only three or four inhibitors, and we show minimal fluctuation in plasma concentration compared to other two. I think that also, those adjustments required compared to the other two in terms of DDI issue. I think for the chronic dosing patient, like many hematology malignancies, safety and tolerance and drug-drug interaction risk are important differentiation. Let's also look at the key data in the US trials. In the MDS, lisaftoclax as studied in frontline produced overall response rate 80% and 50% in relapse RR MDS patient. More importantly, we have a 40% CR rate. 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.

Speaker #4: The only three or four inhibitors, and we showed minimum fluctuation in plasma concentration compared to the other two. I think also the low dose adjustment is required compared to the other two and, you know, in terms of the DDI issue.

Speaker #4: I think for the chronic dosing patient, like many hematology malignancies, safety and tolerance and drug-drug interaction risk are important differentiators. Let's also look at the key data.

Speaker #4: In the U.S. trials, okay, in the MDS, the SAILOR class with azacitidine in frontline produced an overall response rate of 80%, and 50% in relapsed or MDS patients.

Speaker #4: And more importantly, we have a 40% CR rate, okay, and the time to response is also really short. Here, we also highlight two representative real-world cases in high-risk MDS.

Speaker #4: Since it was launched last year in China, in the first case, a 71-year-old patient achieved CR after two cycles with rapid hematological recovery. In the second case, a patient had a poor response and failed the venetoclax class, and then achieved CRi within just 14 days after switching from the venetoclax class.

Dajun Yang: In the first case, a 71-year-old patient achieved a CR after 2 cycles with a rapid hematological recovery. In the second case, a patient with poor response and failed venetoclax, 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/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's important all those trials actually with the patient in US and Australia. This is not the clinical data from China. As we previously indicated, in the case of patient who failed the venetoclax, which is truly a mathematical need globally, we still see a 31.8% overall response rate with no cases of tumor lysis syndrome.

Speaker #4: These cases provide encouraging indications of clinical activity, including in patients previously exposed to the venetoclax class. Let's also look at the AML case. The overall CR/CRi rate was 72%, with a 61% MRD-inactive rate.

Speaker #4: Response was 100% with patients with MPM1 mutation, and 83% in the IDH2 mutation. I think it's important—all those trials actually with patients in the US and Australia.

Speaker #4: This is not the clinical data from China. As we previously indicated, in the case of patients who failed the venetoclax class, which is truly a market lead globally, we still see a 31.8% overall response rate.

Speaker #4: With no cases of tumor lysis syndrome. Same target, same pathway, and the class remains active, I think—at least, you know, based on the current clinical data of resistance to BCL2 inhibitor, the majority are not due to new mutations.

Dajun Yang: Same target, same pathway, and the lisaftoclax remains active. I think at least based on the current clinical data of the resistance to BCL-2 inhibitor, majority are not due to new mutations, but MCL-1 upregulation and some also with the BCL-XL upregulation. So I think that explains partially why the same AML patient failed venetoclax. The lisaftoclax can still achieve activity. So I think that those reflect the key differentiation in the downstream resistance profile and represent meaningful clinical opportunity. But of course, more importantly, with the better safety profile and the lower risk of DDI, also provide more opportunity for combination. In our case, combination with olverembatinib would overcome venetoclax resistance in AML. Turning to the second pillar of product strategy, olverembatinib.

Speaker #4: But MCL1 upregulation, and some also with BCL-XL upregulation. So I think that explains partially why the same, you know, AML patient who failed the venetoclax decitabine class can still achieve activity.

Speaker #4: So I think those reflect key differentiation in the downstream resistance profile and represent meaningful clinical opportunity. But of course, more importantly, with the better safety profile and the lower risk of DDI, it also provides more opportunity for combination and, in our case, combination risk or alternative to overcome venetoclax resistance in AML.

Speaker #4: Turning to the second pillar of product strategy, or alternative, I also want to highlight why we believe this can be a best-in-class, third-generation BCL-2 inhibitor for patients with CML in the second line or later settings.

Dajun Yang: I also want to highlight why we believe this can be a best-in-class third-generation BCR-ABL inhibitor to patients with CML in the second-line or late settings. This has already been approved and highly de-risked asset with several years of clinical and real-world use in China. We receive a validation from Takeda as they hold exclusive option to license olverembatinib outside Greater China and certain other territories. This was entered with Takeda about 2 years ago. Globally, the most important study for the CML is POLARIS-2. Part A enroll chronic phase 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.

Speaker #4: This has already been approved and highly de-risks the asset, with several years of clinical and real-world use in China. We received validation from Takeda, as they hold an exclusive option to license or co-develop outside Greater China and certain other territories.

Speaker #4: This was entered with Takeda about two years ago. Globally, the most important study for CML is Polaris-2. Part A enrolls chronic phase patients who have received at least two prior TKIs, randomized or as an alternative against bosutinib.

Speaker #4: This is clear by FDA and EMA. And there's also Part B, which evaluates our alternative in patients with the T315i mutation. As you know, bosutinib doesn't have activity, so that's the single-arm trial.

Speaker #4: Overall, you can see this is a difficult second-line patient population, which we believe our alternative can be most differentiated in. Besides the CML, our alternative also has strong activity in Ph-positive ALL, so Polaris-1 is also important. This is our global Phase 3 study in newly diagnosed Ph-positive ALL, again both cleared by the FDA, EMA, and CDE, and also with Breakthrough Therapy designation in China.

Dajun Yang: 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 ALL. So POLARIS-1 is also important. This is our global Phase III study in newly diagnosed Ph-positive ALL. Again, both cleared by FDA, EMA, and CDE, and also with breakthrough therapy designation in China. We have already shown strong Part A data at ASH as an 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. Elias Jabbour at MD Anderson. This actually was conducted 4 or 5 years ago. Dr. Elias Jabbour, as you know, is a leading investigator in CML and also Ph-positive ALL. In this particular study, we enroll 62 heavily pretreated CML CP patients.

Speaker #4: We have already shown strong Part A data at ASH as an oral presentation last year, and we continue to advance the global study. Let's look at some of the important breaking studies led by Dr. Ali Jabou at MD Anderson.

Speaker #4: This actually was conducted four or five years ago, and Dr. Ali Jabou, as you know, is a leading investigator in CML and also Ph-positive AL.

Speaker #4: In this particular study, we enroll 62 heavily pretreated CML CP patients. More than half have achieved at least have received at least four prior TKI.

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

Speaker #4: There are like four or fifth line and half of them have received the ponotinib. And third of them have T315 mutation. I think with this really you know poor baseline patient population we achieved the MMR as a single agent 42.9% in ponotinib resistant patients 33% in acetaminophen resistant patients and more importantly 27% in patient who failed both ponotinib and acetaminophen basically those are the patient with any with no other options but single agent or alternative have pretty good efficacy.

Speaker #4: I think this treatment again strengthens, you know, 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 patient has been using our alternative for almost 10 years, since October 2016. And in this particular patient trial, the longest patient treated in the US is over three years, with a manageable safety profile.

Dajun Yang: In this particular patient trial, the longest patient treated in the US 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 in this year reported, in a prospective control data, in the second line, late-line setting, showing a clear benefit from switching to olverembatinib, a type of evidence that remains uncommon in this patient population. I think the differentiation, you can see, is really dramatic, right? 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 two TKI.

Speaker #4: Let's turn to slide 16. I want to share some more recent data. I think one case is the second-line trial strategy, where the alternative demonstrated a 47.6% MMR rate as a single agent.

Speaker #4: More importantly, new data just last in this year, reported in a prospective controlled study in the second-line or later-line setting, showed a clear benefit from switching to or using an alternative.

Speaker #4: The type of evidence 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 or alternative, the MMR rate remains only 10%.

Speaker #4: I think that's a huge benefit in terms of, for the patients in late-line CML. Those patients actually, you know, have been treated with at least two TKIs, some of those also with asciminib or alternatives. The six-month MMR rate was 54%, and then even higher at 57% at 12 months.

Dajun Yang: Some of those also with asciminib. Olverembatinib delivered 6 months 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. Also important safety profile in terms of AEs. Let's turn into slide 17. I think that the benchmark is important because the landmark changed over the last 2 years. I think in addition to at least 2 years ago, the only competitive product we consider is the asciminib, but now there is two drug turns, 701 and 11001, in the study in the US. First, I think the most important one, we are the only one have long-term evidence that other program doesn't yet have, as those are still in the phase I or early phase II.

Speaker #4: Those that didn't switch remain at only a low 20% response. I think, you know, as you can see, there's a huge benefit for patients if they switch to the alternative.

Speaker #4: And also, importantly, the safety profile in terms of AEs. Let's also turn to slide 17. I think the benchmark is important because of the landmark change over the last two years.

Speaker #4: I think, in addition to at least two years ago, the only competitive product we considered was acetaminophen. But now there are two drug terms, 701 and 11001, in the study in the US.

Speaker #4: Okay. But first, I think the most important point is that we are the only ones who have long-term evidence, which other programs don't yet have, as those are still in phase one or early phase two.

Speaker #4: And we have, you know, six years of follow-up for patients who are in the second line, and 10 years for the first line in the phase one trial.

Dajun Yang: We have 6 years follow-up for patients who are in the second line, and 10 years for the first line, the phase I trial. We are the only one have controlled the comparative data set. Those are new requirement from FDA in terms of Project Optimus. So you have to run the RCT trial in order to getting the NDA approved. Another important differentiation in the CML patient population is really the baseline, right? You can see the patient treated with olverembatinib are more late-line, heavily pretreated, and also with the mutations. I think those data clearly demonstrated olverembatinib as the potential drug of choice in the second line of CML of the patient who failed the most advanced available TKI. I think I will show you a few more study in the control in more details on the next slide.

Speaker #4: And we also are the only ones who have controlled the comparative data set. Okay, those are new requirements from the FDA in terms of Project Optimus.

Speaker #4: So you have to run the RCD trial in order to you know getting the NDA approved. Another important differentiation in the CML patient population is the the really the baseline right so you can see the patient treated with or alternative are more late line you know heavily pretreated and also with mutations I think they those data clearly demonstrated or alternative as the potential the drug of a choice in the second line of CML.

Speaker #4: After the patient who failed the most advanced available TKI. And I think I will show you a few more studies in the control in more detail on the next slide.

Speaker #4: Slide 18 is a real-world analysis of 69 blast crisis CML patients who went on transplant, and 26 were treated with other alternatives, and 43 were treated with first- and second-generation TKIs.

Dajun Yang: Slide 18 is a real-world analysis of 69 blast crisis CML patients who went on transplant, and 26 was treated with the olverembatinib, and 43 with the first and the second generation TKI. 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 the no relapse mortality 11% versus 23%. These are the two separate patient cohorts in a retrospective real-world analysis, not a randomized comparison. But again, demonstrate important differentiation of olverembatinib in larger patient population on the 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.

Speaker #4: So the OR alternative group entered transplant in deeper molecular remission. MMR rate was 53.8% versus only 16%, and the CMR rate was 23% versus 4.7%. The OR alternative also had a more favorable survival outcome: one-year overall survival of 89% versus 71%, and the no-relapse mortality was 11% versus 23%.

Speaker #4: These are two separate patient cohorts in a retrospective, real-world analysis. Not a randomized comparison, but again, they demonstrate important differentiation or alternatives in a large patient population.

Speaker #4: And how to treat CML patients. Let's also take a look at the combination strategy. In the patient in the polaris one in with low intensity chemotherapy in front line I think the polaris one three key important differentiation that the the data one this is front line newly diagnosed PH positive AL in most cases around the world chemotherapy still required because the aggressiveness nature of the PH positive AL in the registration trial design we conduct the part A with the low intensity chemo as you can see this demonstrate MRD inactive CR rate about 63%.

Dajun Yang: One, this is a frontline newly diagnosed Ph-positive ALL. In most cases around the world, chemotherapy is still required because of the aggressiveness nature of the Ph-positive ALL. In the registration trial design, we conduct the part A, with the low-intensity chemo. As you can see, this demonstrate MRD negative CR rate about 63%. This is almost double the ponatinib in the same patient population, the PhALLCON trial, about 34%. Of course, in the trial data, the imatinib only 17%, dasatinib is only about 20-plus percent. So this clearly demonstrate, in the registration trial study, olverembatinib is the best among the current treatment option. We also try to enter the chemo-free registration trial.

Speaker #4: This is almost double the polarity in the same patient population as the FALCON trial, about 34%. Of course, in the real—in the trial data, the imaginable is only 17%, the certain is only about 20-plus percent.

Speaker #4: So this clearly demonstrates in the registration trial setting that our alternative is the best among the current treatment options. We are also trying to enter a chemo-free registration trial. Currently, we have data from the oral report at ASCO by Dr. Elijah Boo from MD Anderson, demonstrating that if you combine with Bruno, we can achieve an 80% MRD inactive rate and a 91% CR/CRI.

Dajun Yang: Currently, we have data from the oral report at the ASCO by Dr. Elias Jabbour around MD Anderson, demonstrate that if we combine with the blinatumomab, we can achieve 80% MRD negative rate and a 91% CR/CRi. We also demonstrate importantly in the pediatric RR Ph-positive 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 achieve 89% overall response rate after cycle 2, day 15, and all complete response in oral chemo-free regimen. I think that this combination data is key because this is two already active agent, chemo-free, in the pediatric ALL setting. Moving on to the APG-115, another asset in our portfolio, small molecule targeting MDM2/p53. It actually holds six FDA ODD, and two rare pediatric disease designation.

Speaker #4: We also demonstrate, importantly, in the pediatric RR PH-positive ALL patients, actually those data have been available and were first reported two years ago. We continue to see benefit of safety and overall response. I think, very impressively, we achieved an 89% overall response rate after cycle two, day 15, and all complete responses in an oral chemo-free regimen.

Speaker #4: I think this combination data is key because this is two orally active agents, chemo-free, in the pediatric AL setting. Moving on to APG-15, another asset in our portfolio, a small molecule targeting MDM2 and PP3.

Speaker #4: It actually holds six FDA ODDs and two rare pediatric disease designations. This has actually been in our portfolio for a while, as there is no approved product yet globally targeting the MDN2 PP3.

Dajun Yang: This actually has been conducted in our portfolio for a while, as there's no approved product yet globally, targeting the MDM2/p53. As you know, p53 is one of the most important tumor suppressor gene. But I think that you do see some recent progress that Ipsen acquired Kartos MDM2 inhibitor, and with actually pretty decent $450 million up front and up to $1.75 billion, including milestones for phase III program in myelofibrosis. I think that there is a probably potential for the MDM2/p53 inhibitor combined with the JAK inhibitor in that actually trial as an add-on strategy. I think that data is encouraging. We'll also currently do that trial with MF patients. So, again, this remain wholly owned by us. And in the ASCO, we presented encouraging data for APG-115 in combination with the Giosova in the pediatric soft tissue sarcoma patients.

Speaker #4: As you know, PP3 is one of the most important tumor suppressor genes. But I think you do see some recent progress, that Ipsen achieved—acquired a CATOS MDN2 inhibitor, and with actually pretty decent $450 million upfront and up to $1.75 billion including milestones for a Phase III program in myelofibrosis.

Speaker #4: I think there is probably potential for the MDN2 PP3 inhibitor combined with the JAK inhibitor in that ACTUAL trial as an add-on strategy. I think that data is encouraging. We are also currently doing that trial with MF patients.

Speaker #4: So again, this remains wholly owned by us, and in the ASCO we presented encouraging data for APG-15 in combination with the serva class in pediatric soft tissue sarcoma patients.

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

Speaker #4: Globally, pediatric rhabdomyosarcoma and other soft tissue sarcomas are truly a major unmet medical need. In that setting, we demonstrate good combination safety and an impressive 23.5% response rate, and also a 70% disease control rate.

Speaker #4: I think those are encouraging data in the clinic that demonstrate the already active agent from Ascentage. I think in the interest of time I'll try to focus mostly on the key data, and here's a slide to show you that the cornerstone asset of VCR2 inhibitor resolver class is combinable with three other targeted small agents already active.

Speaker #4: I think, as we all know, as mentioned, the main reason for BCL2 resistance is the upregulation of MCL1. So, we have demonstrated that our alternative actually can indirectly downregulate MCL1.

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

Speaker #4: We not only have preclinical data, but now have clinical data to demonstrate that combination of the—or alternative with the server class—can show the synergy. More importantly, not just in CML or Ph-positive AL, but also in patients with AML or MDS and the Ph-negative AL, especially for those patients who fail the vanilla class in AML. And we have clinical data to demonstrate that, in addition to what we showed before in the Ph-positive AL.

Speaker #4: And again, with MDN2 PP3 inhibitor APG-15, now we have clinical data to demonstrate the safety and efficacy, especially in those hard-to-treat soft tissue sarcoma patients. We are also moving into the DLBCL, AML, and MF. Part of the MOA for this combination is the synthetic lethality. Again, we are the only company worldwide to have all three assets wholly owned by Ascentage.

Speaker #4: In the interest of time, I don't have much, you know, data to show, but I can tell you that our BTK degrader APG-3288 has advanced well in the Phase 1 setting in both the US and China.

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

Speaker #4: Across the B cell malignancies who previously exposed to BDK inhibitors, I think we can stay tuned for the progress for both oncology and the non-oncology indications with the BDK degrader.

Speaker #4: I think that's all the highlights of R&D, and let me turn the call over to our CFO, Dr. Vid Misera, for the review of our financial results.

Veet Misra: Great. Thank you, Dr. Yang. Good morning, everyone. Turning to our financial results, the H1 of 2026 was another period of continued commercial growth and investment behind our global development programs. Total revenue was USD 44.5 million, compared to USD 32.6 million in the H1 of 2025, representing an increase of USD 11.9 million or 29.3% on a constant exchange rate basis. Product sales growth has been our main driver, as indicated by USD 41.6 million of product sales compromising our total revenues. During the H1, we continued 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 USD 102.8 million, compared to USD 73.8 million in the H1 of 2025, representing an increase of USD 29 million or 32% on a constant exchange basis.

Speaker #1: Great. Thank you, Dr. Young. 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.

Speaker #1: 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.

Speaker #1: Product sales growth has been our main driver, as indicated by, you know, $41.6 million of product sales comprising our total revenues. During the first half, we continued to expand our commercial reach and invest behind both products.

Speaker #1: 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.

Speaker #1: Representing an increase of $29 million, or 32%, on a constant exchange basis. As planned, this was our expenditure to execute on our high priority to advance enrollment in multiple global registration trials.

Veet Misra: As planned, this was our expenditure, to execute on our high priority to advance enrollment in multiple global registration trials. Selling and distribution expenses were $33.4 million, compared with $19.2 million in the H1 of 2025, representing an increase of $14.2 million or 64.3% increase. This was driven by marketing and commercial investment behind our products. Administration expenses were $17.5 million compared to $13.9 million in the same period last year, primarily due to RSU expense. Turning to our balance sheet, we are pleased to report cash balances were $279.4 million as of 30 June 2026, as well as reaffirming our cash guidance runway through 2027, as we have said before. This funds us through multiple key registrational studies ongoing globally.

Speaker #1: 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 a 64.3% increase.

Speaker #1: 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.

Speaker #1: Primarily due to RSU expense. Turning to our balance sheet, we're pleased to report cash balances were $270.3 million as of June 30th, 2026, as well as reaffirming our cash guidance runway through 2027.

Speaker #1: As we've said before, this funds us through multiple key registrational studies ongoing globally. To emphasize, we are funding nine registrational programs, and are currently taking initial steps to build a commercial organization in the US. We remain on target for investments required at the appropriate time to fulfill our global strategic objectives.

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

Speaker #1: Thank you, and with that, I'll turn the call back to Dajun for his closing remarks. Dr. Young.

Speaker #2: Great. Thank you Vid. So I think they with the overall R&D highlight and the financial update as you can see our last slide to show we have seven active products in the clinic with two of them already landed approved in China and but more importantly with this already active target agent we cover all majority of him malignancies from the CL AL to the CML AML MDS and also with clinical activities in potentially multi myeloma and the DRBCL.

Dajun Yang: Great. Thank you, Vi. I think that with the overall R&D highlight and the financial update, as you can see our last slide, to show we have seven active products in the clinic, with two of them already landed, approved in China. More importantly, with these already active target agent, we cover all majority of heme malignancies, from the CLL, ALL, to the CML, AML, MDS, and also with clinical activities in potentially multiple myeloma and 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 is all for the brief update with the key data and the financial results. Thank you all for joining us, and also our team.

Speaker #2: I think moving forward, our goal is to focus on the current global registration trials and reach the NDA stage, and build a strong commercialization team outside China as well.

Speaker #2: And to become a global player in the hematologic malignancies globally. I think that's all for the brief update with the key data and the financial results. Thank you all for joining us, and also our team. I think now we are open for the Q&A.

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

Speaker #1: Thank you.

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

Speaker #3: At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen.

Speaker #3: When it is your turn, you will receive a message on your screen from the host allowing you to talk. You will then hear your name called. Please accept, unmute your audio, and ask your question.

Speaker #3: We will wait one moment to allow the queue to form. Our first question will come from the line of Brian Chang with J.P. Morgan.

Speaker #3: Please unmute your line and ask your question.

Speaker #4: Hey guys thanks for taking out questions this morning. And Fazlan James welcome to the team. Just to start off in China you know can you talk about how we should think about the NRDL listing for specifically Lysaptoclax later this year can you talk a little bit about you know 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 follow up.

Brian Chang: Hey, guys. Thanks for taking our questions this morning. Franklin 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 is the progress that you have been seeing in China, how should we think about the next update related to the NRDL listing? Then we have a couple follow up. Thank you.

Speaker #4: Thank you.

Speaker #2: Thank you, Brian. Really good question. So, Lysaptoclax was approved in China in July last year. We are the first domestic BCL-2 inhibitor approved in China.

Dajun Yang: Thank you, Brian. A very good question. lisaftoclax was approved in China July last year. We are the first domestic BCL-2 inhibitor approved in China, also we are the only one, the first one, approved in terms of post-BTK, RR CLL/SLL patients in the registration trial. That was a tough trial, but we demonstrated good safety efficacy, we clearly show the differentiation versus venetoclax or darnotclax in terms of the only approved daily dose turn up with a clear safety profile and a lower risk of DDI. I think if you are looking not just at clinical data, but the NRDL reimbursement, less hospitalization, less risk, 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.

Speaker #2: And also, we are the only one, the first one approved in terms of post-BDK, R/R CLL/SLL patients. In the registration trial, that was a tough trial, but we demonstrated good safety and efficacy, and we clearly showed the differentiation versus venetoclax or serentoclax in terms of the only approved daily dose and up.

Speaker #2: With a clear safety profile and lower risk of DDI, I think if you're looking at not just clinical data but also the NRDL reimbursement—you know, less hospitalization, less risk, and also convenience—all are important favorable factors for the NRDL consideration.

Speaker #2: 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.

Speaker #2: This year, the timeline is actually a little bit ahead of the previous timeline. Currently, there are two groups—NRDL experts, officials, and those health economics experts—who are conducting meetings and reviews right now.

Dajun Yang: This year, the timeline is actually a little bit ahead of previous timeline. As currently, there are two groups, NRDL experts, officials, and those health economics experts are conducting the meetings, reviews right now. So we may call up to a meeting with the experts later this month or early September. Then with the final, we are very confident we will get NRDL coverage for these indications in China. The concern we have or worry is working with the expert is the final price. Of course, venetoclax is already covered for different indication AML in China. It is probably a benchmark. I think we are confident we will have coverage for this indication, which is important in China. The NRDL is not just a reimbursement, but the ticket to enter the hospital. Majority of hospital in China rely on the NRDL approval to enter the hospital in terms of prescription.

Speaker #2: 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 this indication in China.

Speaker #2: Probably the only concern we have when working with the expert is the final price. But of course, Venetoclax is already covered for a different indication, AML, in China, which is probably a benchmark. But I think we are confident we'll have coverage for this indication.

Speaker #2: Which is important in China, the NRDL is not just a reimbursement, but the ticket to enter the hospital. The majority of hospitals in China rely on NRDL approval to enter the hospital in terms of prescription.

Speaker #2: And in case of CRL SL this is a chronic dosing patients reimbursement by NRDL means they can reduce their you know pay you know out of pocket payment but the average two third 60 70% in certain regions the NRDL coverage can up to 90%.

Dajun Yang: 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 two-third, 60% to 70%. In certain regions, the NRDL coverage can up to 90%, so I think that is a huge benefit to the patients in chronic leukemia setting.

Speaker #2: I think that's a huge benefit to patients in the chronic leukemia setting.

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

Speaker #4: Great. Maybe just also turning to your ongoing clinical studies—curious if you can talk about what's going on with the Polaris One and Glor trials specifically. How's enrollment looking, and do you have any sense of how we should think about the timing of the next data readout and the potential pathway to NDA filing?

Speaker #4: How should we think about the timing of those milestones?

Speaker #2: So, I think for those questions, maybe we have our CMO, Dr. Dai, on the call. Maybe Dr. Dai can give some answers first. Dr. Dai?

Dajun Yang: I think for those questions, maybe we have our CMO, Dr. Dai, on the call. Maybe Dr. Dai can give some answer first. Dr. Dai?

Speaker #5: Sorry, Brian. So regarding the Growth Force study, right? Sorry, I heard somebody else's question. Could you please repeat the question?

Yifan Zhai: Sorry, Frank. Regarding GLORA-4 study, right? Sorry, I was addressing somebody else's question. Could you

Brian Chang: Yeah

Yifan Zhai: repeat the question?

Brian Chang: No problem. Yeah, 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 when we are going to get the final data cut to file for the NDA?

Speaker #4: No problem. Yeah, no, just curious how you know how the enrollment is going in the global studies like Polaris One and also the global studies.

Speaker #4: For Lysaptoclax you know how's enrollment going and do you do you have a better sense of how you know when we're going to get the final data cut you know to file for the NDA?

Speaker #5: So regarding all those global registration trials, the team works very hard and tries to complete their enrollment as soon as possible. So it's still under the plan. In particular, the Growth Force study perhaps is under the radar, and everybody is paying particular attention to that global registration trial.

Yifan Zhai: Regarding all those global registrational trial, the team work very hard and try to complete the enrollment as soon as possible. It is 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 Q2, Q3, and actually already announced yesterday, we already complete the enrollment for Q2. I am waiting for the data review mature on Q3, also very close, and the remaining, we plan to complete the enrollment either by the end of this year or the early next year.

Speaker #5: Regarding GLOR 2, GLOR 3—the announcement was actually made yesterday that we have already completed the enrollment. For GLOR 2, we are waiting for the data to mature. GLOR 3 is also very close, and for the remaining, we plan to complete the enrollment either by the end of this year or early next year.

Brian Chang: Great. Thank you.

Speaker #4: Great. Thank you.

Speaker #2: Maybe let me add a few points to what Ifan said. So, you know, we have said yesterday in the Hong Kong call that we completed the enrollment for the GLOR2, which is frontline CRL SL setting combination with other setting and with fixed duration.

Dajun Yang: Maybe let me add a few points to what Yifan said. We have said yesterday in the Hong Kong call that we completed the enrollment for the GLORA-2, which is a frontline CLL/SLL setting, combination with azacitidine, and with fixed duration. Of course, that one is not with the FDA because of the control arm is the chemoimmunotherapy. That is also over 400 patient enrollment, demonstrating our capability in the clinical operation. 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 are a few key points also important to share. One is, this is the frontline. The frontline patient with high-risk MDS. In the trial design, similar to the VERONA, the combo with the Aza versus the Aza alone.

Speaker #2: And of course, that one is not with the FDA because the control arm is the chemoimmunotherapy. But that's also over 400 patients enrolled, demonstrating our capability in clinical operations.

Speaker #2: And GLOR 3 is the AML combo with ASA versus ASA alone. We are in the final stage of closing the enrollment. The GLOR 4, obviously in the high-risk MDS, many people are watching closely. I think a few key points are also important to share.

Speaker #2: One is, this is the frontline, okay? The frontline patient with high-risk MDS. In the trial design, similar to the Verna, that combo with ASA versus ASA alone.

Speaker #2: And this has been cleared by FDA, EMA, PMDA, and in China. And globally, not because Verna failed, but also another BCR2 inhibitor—Verna class is not on the MDS, not on the registration trial.

Dajun Yang: This has been cleared by FDA, EMA, PMDA, and China. Globally, not because VERONA failed, but also another BCL-2 inhibitor, venetoclax, is not on the MDS, not on the registration trial. Globally, we are the only phase III registration trial for the high-risk MDS. There is no target drug approved in the high-risk MDS in the last 20 years. This remains globally an 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. 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. The good problem to have, we are looking for potentially three NDAs to file the second half of next year.

Speaker #2: And globally, we are the only Phase 3 registration trial for high-risk MDS. There's no targeted drug approved in high-risk MDS in the last 20 years.

Speaker #2: So this remains globally a mathematical need, and the enrollment is doing well because experts around the world in MDS are really enthusiastic and all want to help patients with high-risk MDS.

Speaker #2: So overall, I think to summarize, we anticipate, as we said before, the enrollment for Glor 4 and Polaris 1 plus 2 could complete by late this year or early next year.

Speaker #2: And it's a good problem to have. We're looking to potentially file three NDAs in the second half of next year.

Speaker #4: Great. And if I can squeeze one point 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 you know investors can make a good comparison against other BTK degraders do you have a benchmark internal benchmark of efficacy early on and thanks for taking our questions today.

Brian Chang: Great. 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 an internal benchmark of efficacy early on? Thanks for taking our questions today.

Speaker #2: Yeah, I think in all of that, the BTK as a target is really competitive, really crowded, and there are many inhibitors, covalent and non-covalent, on the market, and some are doing really well.

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

Speaker #2: But the BTK degrader does have advantages, at least with some of the current, even up to Phase 3 data. So we conducted careful preclinical studies to compare our drug, 3288, with the other two from Nurix or B1, and ours has better selectivity and stronger efficacy.

Speaker #2: But that, again, is in the preclinical setting. Currently, I think in the Phase 1, we're moving along very well in terms of dose escalation for safety, but more importantly, first, those are all BTK-exposed patients.

Speaker #2: Okay. It doesn't matter, covalent or non-covalent, and we want to show some response in those patient populations first, right? That's important; that's the key differentiation for the degrader. Second, we probably will take some patient populations—the indications where currently BTK inhibitor is not really active—so more importantly, combination with our BCR2 inhibitor.

Dajun Yang: Second, we probably will take some patient population, the indications that currently BTK inhibitor is not very active. More importantly, combination with our BCL-2 inhibitor, I think that one example in that setting may be the DLBCL, because so far, the BTK inhibitor hasn't shown good activity as a single agent in that DLBCL setting. Of course, there are also a lot of data that combined with the BCL-2 may have better readout in this patient population. Another potential one, but we don't have data to share yet, is in the non-oncology indication. I think that there are many autoimmune indications could be benefit with the BTK degrader.

Speaker #2: I think the one example in that setting may be DLBCL. So far, the BTK inhibitor hasn't shown good activity as a single agent in that DLBCL setting.

Speaker #2: And of course, there are also a lot of data to combine with BCR2 that may have, you know, better readout in this patient population. Another potential one, but we don't have data to share yet, is in the non-oncology indication.

Speaker #2: I think there are many autoimmune indications that could benefit from the BDK degrader.

Speaker #4: Great. Thank you, Sachin, and congrats on the progress.

Brian Chang: Great. Thank you, Dajun, and congrats on the progress.

Speaker #2: Thank you.

Dajun Yang: Thank you.

Speaker #1: Your next question will come from the line of Byron Amin with Piper Sandler. Please unmute your line and ask your question.

Operator: Your next question will come from the line of Byron Ammon with Piper Sandler. Please unmute your line and ask your question.

Speaker #3: Yeah. Hi, team. Thanks for taking my questions. Maybe if I could just start with the POLARIS-1 and POLARIS-2 trials—can you just provide us with an update in terms of when we can expect data from both studies?

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

Speaker #2: Again, for that question, Ifan, our CMO, can address it first.

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

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

Speaker #5: We just addressed the same question. Let me repeat it. So currently, we're very active in rotations and plan to complete the enrollment either by the end of this year or early next year.

Speaker #5: Plan to submit the NDA next year.

Speaker #2: Yeah. I think they just add a little bit for the Polaris 2—the filing NDA is six months MMR rate after the last patient in.

Dajun Yang: Yeah, I think that they just add a little bit. For the POLARIS-2, the filing NDA is a 6-month MMR rate after the last patient in. Of course, we already demonstrated very strong data in the MMR rate for this patient population and we are confident on that. But the key, of course, is the finishing enrollment. For the POLARIS-1, the filing of NDA with FDA is the 3 months MRD negative CR rate. 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 two NDAs second half of next year.

Speaker #2: So, of course, we already demonstrate very strong data in the MMR rate for this patient population, and we're confident on that. But the key, of course, is to finish enrollment.

Speaker #2: And for the Polaris-1, the filing of the NDA with the FDA is for the three-month MRD-negative CR rate. So, I think, again, the target enrollment is on track, and with these six-month or three-month endpoints for the NDA filing, we're looking for potential filing of those two NDAs in the second half of next year.

Speaker #3: Great. And maybe just to follow up on a couple of questions. For Oliver and Batneb, when could we expect to see TK make a decision on this option, on the license?

Byron Ammon: Great. Maybe just follow up on a couple of questions. For olverembatinib and ponatinib, when could we expect to see Takeda make a decision on its option on the license? That is the first question on the global license. 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. 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?

Speaker #3: 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 paid hospitals in China?

Speaker #3: 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 this year, and are you planning to evaluate also in the MS setting?

Dajun Yang: Maybe I will answer your last question first. The 3288 is still ongoing in the phase I trial, US, China. I think because this is a dose escalation, and the cutoff for the ASH already ended, so we do not anticipate to present 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. Again, we are conducting several autoimmune indications, demonstrate good preclinical activities. Because of the non-oncology trials, in the phase I health volunteer, you do need a placebo control, right? So that is 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.

Speaker #2: Maybe I'll answer your last question first. So, the 3288 is still ongoing in the Phase 1 trial in the US and China. I think because this is dose escalation and the cutoff for the ASH has already passed, we don't anticipate presenting Phase 1 data this year at ASH.

Speaker #2: But the progress is doing well. Perhaps we can have some to share, maybe at IHA next year in terms of timing for the phase 1 data.

Speaker #2: And again, we are conducting several autoimmune indications that demonstrate good preclinical activities. And because the non-oncology trials in the Phase 1 healthy volunteer study do need a placebo control.

Speaker #2: Right. So that's where we are working to get the IND filed for the non-oncology indications, including the MS. But that data will come a little bit later because we're making it placebo-controlled.

Speaker #2: 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, we entered the global exclusive partnership option agreement two years ago in 2024, and that is again exclusive global outside China and some territories. For that, Takeda, back two years ago, paid $100 million upfront and made a $75 million equity investment.

Dajun Yang: But we do anticipate the IND to be filed soon with the autoimmune indications. For your first question, I think the Takeda deal, as you know, that we entered the global exclusive partnership option agreement 2 years ago, 2024, and that is, again, exclusive global outside China and some territories. For that, Takeda, about 2 years ago, paid $100 million upfront and $75 million equity investment. There is also a total up to $1.2 billion aggregate when they exercise the option and a certain milestone payment. Also they tier the royalty rate from 12% to start up to 19%. I think globally, Takeda is a key player in the CML and ALL, after Novartis, obviously. But I think we do believe Takeda is important and a global partner for commercialization olverembatinib and ponatinib.

Speaker #2: And there's also a total up to 1.2 billion aggregate when the excess option and a certain milestone payment. And also the tiered royalty rate from 12% to start up to 19%.

Speaker #2: I think you know, globally, Takeda is a key player in the CML and AL space, you know, after Novartis obviously. But I think we do believe Takeda is an important and global partner for commercialization over maternal, and one of the main reasons for the option agreement is obviously to have a competitive product patented.

Dajun Yang: One of the main reason for the option agreement is obviously to have a competitive product, ponatinib, and the potential antitrust issue. But ponatinib patent will expire early next year. I think that is the key component in the option accesses. 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 still have a second half of time to report.

Speaker #2: And the potential antitrust issue, but the 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 was signed, with the Takeda team. So we are actually working closely together to advance all the enrollment and a lot of KOL outreaches and planning for the commercialization.

Speaker #2: With Gene on board, we are looking forward to working together ahead of the launch with the Takeda team, for the great, you know, potential of Olmatrel in the global market.

Speaker #2: I think you have one more question about the hospital, right? I think that currently, we are doing well in terms of getting the hospital covered.

Speaker #2: I think we 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 the build up close to 400 commercial forces in China.

Dajun Yang: But we are on the track currently bringing the total commercial team about 300, and the goal is to build close to 400 commercial forces in China. I think it is not just the number 400 staff in the commercial team, but more importantly, is to cover 80% of the market potential with the two product in China. I think that is where the 2,000 hospitals number we try to achieve. We are on the track to achieve that with the expanding the commercial team and also the leadership, both in US and China.

Speaker #2: I think it's not just the number—you know, 400 staff in the commercial team—but more importantly, it's to cover 80% of the market potential with the two products in China.

Speaker #2: I think that's where the, you know, 2,000 hospitals number we try to achieve. We are on track to achieve that with the expanding commercial team and also the leadership, both in the US and China.

Speaker #3: Great. Thank you.

Byron Ammon: Great. Thank you.

Speaker #2: Thank you.

Dajun Yang: Thank you.

Speaker #3: Your next question will come from the line of Jeet Mukherjee with U.S. Bancorp BTIG. Go ahead with your question.

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

Speaker #1: Great. Thank you for taking the question. Maybe just to dig a little bit further into some of these upcoming readouts. Just how should we think about setting expectations for Polaris 1, 2, and GLORIA 4?

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

Speaker #1: And then, you know, just turning to Oliver and Batneb—you highlight some of your competitors on slide 17. But if you could just provide some further detail or perspective on what you see as the biggest differences for your molecule versus those competitor agents, on both efficacy as well as safety.

Speaker #1: Thank you.

Dajun Yang: Really great question. But first, based on the preclinical data, our drug is probably among all the TKIs or all 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 happen 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 is also more than one mutation, called a compound mutation, in the same cell. Currently, asciminib, and also those 701 or 11001 do not have those strong data. So olverembatinib is the most potent one and also most active one against wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of lay line CML patients.

Speaker #2: Really great question. But first, based on the preclinical data, our drug is probably, among all the TKIs or all the staff inhibitors, the most potent one against the T315 mutation.

Speaker #2: And also the compound mutation, because in the BCR-ABL gene, the mutation does not just happen in one hotspot. The T315i is considered a gatekeeper mutation. Differentiate those in terms of third-generation BCR-ABL inhibitor.

Speaker #2: But on top of that, there's also more than one mutation, called a compound mutation, in the same cell. Okay. And currently, kinome, and also those terms or 11, do not have those strong data.

Speaker #2: So, overmatinib is the most potent one, and also the most active one against a wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of late-line CML patients.

Speaker #2: So currently, even though CinnaB has proof label in with only US to treat the patient with T315 mutation, but they need a five-time dose.

Dajun Yang: Currently, even though asciminib have approved label, which is only US, to treat the patient with the T315I mutation, but they need a five-time dose, right? Five-time dose, and also in US, that is five times the cost, almost USD 1 million. So I think that in the lay line CML patients with mutations, we do show probably the most potent one. And 11001 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 US, because the Project Optimus, we have those data four or five years ago with the MD Anderson, that we have patient basically unmet medical need, right? Patient who fail both ponatinib and asciminib are the patient with no other treatment options.

Speaker #2: Right. Five-time dose, and also in the US, that's five times the cost—almost a million dollars. So I think that in the late-line CML patients with mutations, we do show probably the most potent one, okay.

Speaker #2: And 11 or turns 701 now with Merck do not have those data. And they also are mostly in the early, you know, phase one or two.

Speaker #2: And in the US, because of Project Optimus, you know, we have those data from four or five years ago with MD Anderson. We have, you know, patients basically on mathematical need.

Speaker #2: Right. Patients who fail both patented and cinemab are the patients with no other treatment options. But because of Project Optimus, if they do not allow the single agent, single arm period of phase two trials for registration, you know...

Dajun Yang: But because of the Project Optimus, FDA do not allow the single-agent, single-arm pivotal phase II trials for the registration. So that is why we have to conduct the RCT. We have to have the control arm, like venetoclax. I think that none of those competitive product have those data or registration trial agreement with the FDA yet. In the real world, the consensus among the CML experts community is you want to give the best BCR-ABL inhibitor to the patient who failed after first-line early, right? You do not want to wait until after four or five lines. You want to give the strong one so the CML patient who achieve deeper response, like MMR, MRD, negative CR, or the MR4 or DMR or 4.5.

Speaker #2: So that's why we have to conduct the RCT. We have to have the control arm, like wasutanib. I think that none of those, you know, competitive products have those data or registration trial agreement with the FDA yet.

Speaker #2: In the real world, the consensus among the CML expert community is that you want to give the best BCR-ABL inhibitor to the patient who fails after first-line therapy, early.

Speaker #2: Right. You don’t want to wait after four or five lines—you want to give the strong one. So, the CML patient who achieves a deeper response, like MMR, MRD, you know, an active CR, or the MR4, or DMR 4.5.

Speaker #2: So, patients who can achieve a deeper response early would be able to achieve TFR, and in certain cases, maybe, you know, drug-free for many years—defined as a clinical cure.

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

Speaker #2: I think that's important. That's why we have a second line data we have the real world data perspective comparative study to demonstrate the over maternal could be the choice of patient who failed front line doesn't matter is a TKI or a cinemab or any other you know allostatic inhibitor.

Speaker #2: That's the goal. That's the key differentiation we have been showing, presented with the clinical data.

Speaker #1: Thank you. Appreciate it.

Jeet Mukerji: Thank you. Appreciate it.

Speaker #2: Thank you.

Dajun Yang: Thank you.

Speaker #3: Your next question will come from the line of Gregory Renza with Truist Securities. Please unmute and ask your question.

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

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

Speaker #4: Greg, good morning, and thank you, Ascentage, for taking my question, and congrats on the progress. My question just to start is on the SAPTACLAX.

Speaker #4: Certainly, when it comes to the commercial trajectory over this year, could you just comment about how that perhaps changed since SONRO has entered the market?

Speaker #4: Are these two drugs competing directly, or is SAPTACLAX, certainly as approved in the post-BTK monotherapy setting, just producing more of a meaningfully different initial patient mix?

Speaker #4: And maybe just comment a bit on the five-day ramp-up, as you've mentioned, and how that's perhaps translating to more measurable real-world advantages in China.

Speaker #4: Thank you.

Speaker #2: Okay. Great question. So, overall, BCI-2 is a very tough target, right? And we have been working on that in the lab for 30 years, and clinically for 21 years.

Dajun Yang: Okay. Great question. Overall, BCL-2 is a very tough target, right? We have been working on that in the lab for 30 years, clinically for 21 years, advanced three products in the clinic, but only the venetoclax made to the market. Again, we always compare with the venetoclax, and that daily dose enough was the 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 CLL/SLL patients, some of the early risk was in the tumor lysis syndrome. That is why venetoclax, and also sonrotoclax went to this weekly dose enough, right? And require hospitalization and close monitoring because of tumor lysis risk.

Speaker #2: Advanced three-product interclinic, but only the so-far cost made to the market. But again, we always compare with another class. And that daily dose enough was a key differentiation in the beginning, where the only one approved to go to the clinical trial and approve the label with the clinical data.

Speaker #2: I think in the CR SL patients, some of the early risk was tumor lysis syndrome. That's why Venetoclax and also SONRO class went to this weekly dose enough.

Speaker #2: Right. And require hospitalization and close monitoring because of tumor lysis risk. But on the other hand, because the VEN class is already on the market—same with the SONRO class—now, the differentiation in the chronic dosing patient, like a CRL, is actually the safety.

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

Speaker #2: Right. If the drug is tolerated well, with less tumor lysis syndrome and less bone marrow toxicity—primarily, in our case, we have a shorter T half—that translates into a better safety profile, less leukopenia, thrombocytopenia, and also much less infection.

Speaker #2: Some of the hematology malignant patients in the clinic, their first presentation is actually an infection, like high-risk MDS, right? And then they found out, actually, the bone marrow is the one that has the cancer cells.

Speaker #2: So, the patient with high risk of infection—it's important you have a lower risk of DDI drug to combine with, right? Not just combine with azacitidine, which is standard of care for high-risk MDS right now, but also, in some cases of marrow disease, especially like multiple myeloma, the combination with antifungal drugs is essential for those patients.

Dajun Yang: Not just to combine with azacitidine, standard of care for high-risk MDS right now, but also in some case of marrow disease, especially the multiple myeloma, the combination with antifungal drug is essential for those patients. I think the key differentiation, as we alluded to before, is less is more. So they compare even with the sonrotoclax now on the market, you see from the label that they even have a higher risk of DDI than venetoclax. Okay? I think that the differentiation in terms of daily dose enough, 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 it reaches to the market.

Speaker #2: I think the key differentiation, as we alluded to before, is "less is more." So, compared even with the SONRO class now on the market, you see from the label that they even have a higher risk of DDI than the vanilla class.

Speaker #2: Okay. So I think the differentiation in terms of daily dosing, enough convenience, better safety profile, tolerance, and lower risk of DDI is important for these chronic dosing leukemia patients.

Speaker #2: I think those are the ones we remain confident will show the, you know, benefit to patients globally once they reach the market.

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

Speaker #4: That that's really helpful. Thank you Dr. Yang and maybe just a question on on the pipeline that you spoke highly of APG-115 and and and that development flexibility that you have with the program as well as 3288 and certainly the synergy potential there with with your portfolio.

Speaker #4: 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?

Speaker #4: Thank you.

Speaker #2: To be honest, it's hard to say which one is our 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, BCI-2 inhibitor.

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

Speaker #2: Right. So one of the challenges for the MDN253 target, that's why currently no approved product yet, is this negative feedback loop and also the requirement of combination.

Speaker #2: We have tried multiple, you know, including the combo with Keytruda in the Phase 2 setting in multiple tumor indications, but we haven't really seen the signal for the registration path.

Speaker #2: Before. But currently we do see now with this combination with the BCI 2 inhibitor clinical benefit and the MOA of synthetic lysality. On the other hand even though it's from the competitive product the colors you know colors compound you know also enter the phase three registration trial with the add on strategy of you know JAK inhibitor in MF.

Dajun Yang: On the other hand, even those from the competitive product, the Kartos compound also entered the phase III registration trial with the add-on strategy of a JAK inhibitor in MF. Obviously, it's encouraging to see Eisai enter the acquisition with potentially $1.75 billion. I think there is a potential, maybe at the end of the tunnel, see finally the MDM2/p53 inhibitor may enter the market or a registration pass. 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 one, the EED inhibitor 5918. We will show the data at the ASH this year. We have completed close to 100 patient phase I trial in informal setting. We are very excited to show this data at the upcoming ASH, that's already submitted.

Speaker #2: And obviously, it's encouraging to see Ipsen enter the acquisition with the potential $1.75 billion. I think there is potential—maybe at the end of the tunnel—to see that finally, an MDM2/3 inhibitor may enter the market or registration path.

Speaker #2: For your question, I think among the pipeline, we have five of them right now. Each one of them has a unique and different strength or differentiation based on the current data.

Speaker #2: Obviously, the two new ones, the ED inhibitor 5918—we will show the data at ASH this year. We have completed, you know, close to a 100-patient Phase I trial in the lymphoma setting. We are very excited to show this data at the upcoming ASH; that's already submitted.

Speaker #2: And for the ED inhibitor, there's also potential in, you know, prostate cancer and some other settings of solid tumors. I think there's a lot of potential in the ED; we're the first one in China, globally the second in the oncology setting, and I think there is a lot of potential in the ED in both hematologic and solid tumors.

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

Speaker #2: And of course, the BDK degraders 3288 is also very exciting in terms of oncology and non-oncology. I think they currently, in addition to the two approved products in China, are globally in registration trials. Clearly, that’s the focus.

Speaker #2: Right. We want to, you know, get the first NDA filed with the FDA and those two products. But as you can see, among the five clinical-stage assets, at least those three I mentioned clearly show a leading advantage globally with clear clinical data. I think those are still early, not reaching the registration trial yet.

Dajun Yang: 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 the favor is hard to say. It is all data-driven, but I think all these three do have very exciting data and a path to registration.

Speaker #2: So, I think we have sufficient resources in terms of budget and clinical team to advance those trials. Again, which one is a favorite is hard to say.

Speaker #2: It's all data-driven. But I think all these three do have very exciting data and the path to registration.

Speaker #4: Yeah. Maybe just to add to that you know as it relates to our presence in China our legacy in China we have you know we're one of the few companies that can de-risk and gain you know real information about how to tactically prioritize our portfolio.

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

Speaker #4: And what to take and execute, you know, in other countries and globally. So I think that that's important to keep in mind about us.

Speaker #4: That's great. Thank you, gentlemen, for all the color, and congratulations again.

Gregory Renza: That is great. Thank you, gentlemen, for all the color, and congratulations again.

Speaker #1: Your next question will come from the line of Mayank Mamtani with B. Riley Securities. Please go ahead with your question.

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

Speaker #2: Yes, Dean. Thanks for taking a question, and I appreciate the helpful detail. A couple of quick questions on Zapflex. I think you were talking about when failure patients' development is being explored.

Mayank Namtani: Yes, team. Thanks for taking our questions and appreciate the helpful detail. A couple of quick questions on lisaftoclax. You were talking about venetoclax 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? On GLORA-4, if you could maybe comment on your expectation for CR rate and TLS, and how maybe the interim OS analysis will be handled in the study if there's anything early built in there. Then I have a follow-up question on POLARIS.

Speaker #2: Could you maybe just touch on you know how quickly you can generate data there? What is the you know patient pool look like? And then on Glora 4 if you could maybe comment on your expectation for you know CR rate and TLS and and how maybe the interim OS analysis would be handled in the study if you if there's anything early built in there.

Speaker #2: And then I have a follow-up question on Polaris.

Dajun Yang: The first question, I think maybe Yifan can answer.

Speaker #3: So, the first question, I think maybe Ifan can answer.

Yifan Zhai: Very great question. Yes, based on our preclinical data, we have reported using the lisaftoclax in combination with olaparib able to overcome venetoclax resistance, which we have previously reported at the ACR. We also use very preliminary data we submitted to this year ASH, and when the data mature, we have data demonstrate the combo able to overcome the venetoclax resistance. The data is preliminary but very exciting, and we submit the abstract to ASH. That's just your question. We in the process in globally, including in China or alpha China in US, 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 venetoclax-resistant MMR population, either using the combo or our other compound APG-1252.

Speaker #5: Very great, great question. Yes. Based on our preclinical data, we have reported using the septal class in combination with overampotenab, able to overcome many class resistance, which we have previously reported at the ACR. We also used very preliminary data we submitted to this year’s ASH, and when the data mature, we have data demonstrating the combo is able to overcome the many class resistance.

Speaker #5: The data is preliminary, but very exciting. We submitted the abstract to ASH, so that addresses your question. We are in the process globally, including in China, outside China, and in the US, and we are making our best effort to enroll more patients with multi-class treatment failure, using different strategies based on the known resistance mechanisms to target this event-resistant AML population.

Speaker #5: Either using the combo or our other compound, ABG-1252. To address your question, the 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.

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

Speaker #5: But but as we I mentioned earlier we plan to complete the enrollment either by the end this year or early next year. Because based on the current design and the dual primary incubator we we we are able to submit the NDA and using the CRA as the primary endpoint.

Yifan Zhai: continue to mature the OS data sometimes next year.

Speaker #5: And then continue to mature the OS data, sometimes next year.

Mayank Namtani: Thank you. I appreciate the detail. 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 have powered the study for. I was also curious because your MMR rates grow over time, 48, 96 weeks, how are you handling crossover from control arm ponatinib there? Do they have option to get your drug, or are they moving on to other trials? What sort of longer-term efficacy we can get there?

Speaker #2: Thank you. I appreciate the detail. And then, a similar kind of question on Polaris too—you know, on the treatment effect for the 24-week MMR rate. If you could maybe just comment on, you know, what you powered the study for.

Speaker #2: And I was also curious, because, you know, MMR rates grow over time—you know, 48, 96 weeks. How are you handling crossover from the control arm and ATNA there?

Speaker #2: Are they do they have option to get the get your drug or or they're moving on to other other trials and and what sort of longer term efficacy we can get there?

Yifan Zhai: Very good question. Based on the current study design, at the beginning, FDA denied our study design to allow patients crossover from the control arm to the investigation arm. Later on, we tried again to request the FDA, finally gave the green light, allow those patient fail from the control arm crossover to olverembatinib. That will make the study more attractive, number 1. Number 2, regarding the endpoints. Currently, we use the 24 weeks, at the 24 weeks MMR rate as the primary endpoint. The basic study design is the power enough and double the MMR rate compared to control arm.

Speaker #5: Very good question. So, based on the current study design, at the beginning actually FDA denied our study design to allow patient crossover from the control arm to the investigational arm.

Speaker #5: But later on, we tried again to request the FDA finally give the green light to allow those patients who failed from the control arm to crossover to olverembatinib.

Speaker #5: So that will make the study more attractive number one. Number two regarding the the endpoints. So currently we use the the 24 weeks at the 24 weeks MMR rate as the primary endpoints.

Speaker #5: So, the basic study design is powered enough and doubled the MMR rate compared to the control arm.

Speaker #2: Okay.

Mayank Namtani: Okay.

Dajun Yang: Also, just to add on, the design of the POLARIS-2, because of the Project Optimus, you have to do the RCT, and you have to have a control arm. In that particular setting, FDA did agree this is a 2 to 1 ratio. Also allow the crossover. Remember, the POLARIS-2 also have the arm B, the mutation with T315I mutation patient only, that we can do the single arm design with the 48 patients. I think that the total POLARIS-2 is 333 patients and enroll well, the 6 months MMR rate for the initial filing of the NDA with the FDA.

Speaker #3: And also, just to add, on the design of the POLARIS-2, in terms of—because of Project Optimus, right? You have to do the RCT and you have to have a control arm.

Speaker #3: But in that particular setting, FDA, you know, did agree this is a 2:2:1 ratio. So, and also allowed the crossover, okay? And remember, the Polaris-2 also has the Arm B—the mutation with T315I mutation patients only—that we can do the single-arm design with 48 patients.

Speaker #3: Okay. So I think the total number of patients in POLARIS-2 is 333, and enrollment is going well. Then, the six-month MMR rate is for the initial filing of the NDA with the FDA.

Speaker #2: Awesome. Thank you. And last one for Veet, if I may—just if you could comment, Veet, on your OPEX trajectory, and you know, if you're getting to peak soon. I know you have a lot of registration studies, so 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.

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

Speaker #2: Thanks for taking your question.

Speaker #3: Yeah great question my honk. So so as I said we we reaffirmed our our cash runway and we're you know happy that we've been adhering to our forecasted spending you know given the scale of our studies.

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

Speaker #3: You know globally multiple countries and you know we're at we're at a point now what we wanted to do for this year was to you know de-risk the balance sheet in 2025 so that we can you know execute on enrollment and this year is the year of execution enrollment is going well you know Dr. Yang and Dr. Xie 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.

Speaker #3: So so all that is going as 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 for the data as well as our multiple NDA filings.

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

Speaker #3: So those are the key expected milestones we have with the cash on our balance sheet.

Speaker #2: Got it. Thank you Veet.

Mayank Namtani: Got it. Thank you, Vi.

Speaker #3: Of course.

Veet Misra: Of course.

Speaker #1: Your final question will come from the line of Michael King with Rodman & Renshaw LLC. Please unmute and ask your question.

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

Speaker #4: Thanks for taking the question. Congratulations on the progress, guys. I wanted to drill down a little bit further on the balance sheet question.

Michael G. King Jr.: Thanks for taking the question. Congrats on the progress, guys. Maybe wanted to drill down a little further on the balance sheet question. If you could talk a little further about capital allocation, because you guys do have a fairly hefty burn rate, and even with the Takeda opt-in, you are going to require a lot of capital.

Speaker #4: You know, if you could talk a bit further about capital allocation, because you guys do have a fairly hefty burn rate. And even with the Takeda opt-in, you know, you're still going to require a lot of capital in highly competitive markets, even with differentiated products.

Michael G. King Jr.: In highly competitive markets, even with differentiated products, you do have entrenched competition. I am just wondering if you feel any urgency to do additional partnerships or other types of arrangements where you could lay off some of the capital allocation demands.

Speaker #4: You do have entrenched competition, so I'm just wondering if you feel any urgency to do additional partnerships or other types of arrangements where you could lay off some of the capital allocation demands.

Speaker #3: Yeah, maybe I can start, or go ahead, Dr. Yang.

Veet Misra: Yeah. Maybe I can start. Or go ahead, Dr. Yang, and then I can

Dajun Yang: No, you go ahead.

Speaker #4: No, no, you go ahead.

Speaker #3: Yeah, in terms of, you know, 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.

Veet Misra: Yeah. In terms of allocation of our total budget to programs, we haven't given that level of attribution. As I stated, we have prioritized so that we can align our spend with expected major milestones and catalysts. Obviously that's what we want 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. 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. Of course, with Faiçal on board, the optionality as it relates to potential partnerships when it makes sense as well.

Speaker #3: So obviously that's the that's what we wanted established. What we have done is you know 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.

Speaker #3: 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 Fazel on board, the optionality as it relates to potential partnerships—when it makes sense—as well.

Speaker #3: So, we are not under pressure to pursue one particular path, which is exactly where we want to be at this point.

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

Speaker #4: Yeah, I think I fully agree. Just to add one more point: our current cash runway, as we have stated before consistently, can support our R&D plan through the end of 2027.

Dajun Yang: Yeah, I think I fully agree. Just add one more point, that our current cash runway, as we stated before consistently, can support our R&D plans through the end of 2027. More importantly, with nine registration trial and four global clear by FDA and EMA, majority of this enrollment are already done. Actually, that's why you see the first 6 months, we have R&D expense of more than 30% increase, primarily due to this heavy enrollment. But the good news is that most part of the cost is already at least more than halfway done. Of course, we remain open, flexible for many options for the fundraising, and also partnership, other source of income. On top of our positive continued growth revenue with the two product sales in China. I think we are really unique.

Speaker #4: More importantly, with, you know, not in registration trial and for global clear by FDA and EMA, the majority of these enrollments are already done. You know, actually, that's why you see the first six months, you know, we have earned expenses—you know, more than a 30% increase—primarily due to these, you know, heavy enrollments.

Speaker #4: But the good news is that most of, you know, part of the, you know, cost is already at least more than halfway done.

Speaker #4: Right. Of course, we remain open and flexible for many, you know, options for fundraising and also partnership and other sources of income, on top of our, you know, positive, continual growth in revenue with two product sales in China.

Speaker #4: I think we're really unique. It's not just because we have, you know, legacy and resources in China, but also steady and growing revenue income from China, and looking forward to the global commercialization and the revenue as well.

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

Michael G. King Jr.: Well, thanks for taking the questions.

Speaker #4: Thanks for taking the questions. Thank you, Mike.

Dajun Yang: Thank you, Mike.

Speaker #1: That concludes the question-and-answer portion of today's call. I will now hand the call back to management for closing remarks.

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

Speaker #4: Thank you all for joining us. I think this internal report again positions us well to be the global player, you know, in the hematologic malignancies.

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

Speaker #4: And more importantly, we are well advanced in terms of all the key registration trials, with the target to complete them by the end of the year or early next year.

Speaker #4: But more importantly, we are in the position—if you look at some of the competitors or the really excellent biotech companies this time last year, okay.

Speaker #4: So I told my team and many investors that Ascentage will be a different company by this time next year. Okay. So we're looking forward to your support, and looking forward to working with our team, investors, and HCPs globally to bring those novel, safe applications and drugs into the global market to help patients with unmet medical needs globally.

Dajun Yang: Thank you all for your attention and support.

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