Thank you, operator. Good morning, everyone.

Thank you for joining today. Welcome to Ascentage Pharma's 2026 interim results and business update call.

I'm Sumedh Sukhatme Nene, 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 six months ending June 30th, 2026. That release and the slide presentation accompanying this call are available in the Investor Relations section of our website.

Turning to our agenda, Dr. Yang will open with a business update, and we will hear briefly from Dr.

Miyara and Mr. Ziegler on the business development and commercial priorities behind our global hematology franchise.

Dr. Yang will then cover our R&D highlights, and Dr.

Misra will review the financials. Dr.

Zhai will also join us for part of the Q&A session. We will then open the line for your questions.

I'd now like to turn the call over to our CEO, Dr. Dajun Yang.

Dr. Yang, you may begin.

Thank you, Sumedh. Thank you all for joining us.

The first half of 2026 advanced a single objective: building Ascentage into a leading global, fully integrated hematology oncology company. We are a company that discovers, develops, conducts global clinical trials, and now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide.

We are currently advancing nine global registrational trials, four of which are cleared by both the FDA and the EMA. The total revenue grew to $44.5 million, up 29% year over year, of which were product sales of $41.6 million on a constant exchange rate basis.

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.

Faouzi as Chief Business Officer and Mr. Jim Ziegler as Chief Commercial Officer.

Both are with us today, and will be sharing preliminary thoughts. Let's look at the next slide.

This slide we have two approved products and the late-stage pipeline that's highly de-risked. Olverembatinib, our third-generation BCR-ABL inhibitor, has been approved CML CP in China since 2021.

Tens of thousands of patients have been treated today. The longest patient on our drug has been 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 registrational trials, including FDA and the EMA cleared, that's an ongoing.

Our plan is to commercialize olverembatinib in the United States and the major pharma markets. Lisaftoclax, our selective BCL-2 inhibitor, is approved as a single agent in post-BTK CLL/SLL.

Globally, we are the second selective BCL-2 inhibitor to reach to the market after decades have passed. However, in the single agent post-BTK CLL, we're actually the first to get approved to the market.

Lisaftoclax have a unique daily dose ramp-up. We're 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 the EMA cleared global registrational trials, GLORIOSA and GLORIOSA-4.

Behind those two, we also have five additional clinical-stage assets, all are conducting trials in U.S. and China and the rest of the world: APG-2449 is a triple kinase inhibitor covering FAK, ALK, ROS1; and the MDM2-p53 inhibitor APG-115; and also targeting both BCL-2 and XL, APG-1252; and the EED inhibitor 5918; and also the new one joining this year to the U.S.

and China phase 1 trial is APG3288, BTK degrader. In light of our mission to build Ascentage into a leading global hematology oncology company, we have strengthened our leadership team in the two areas that determine whether a franchise reaches patients outside China: global business development and commercialization.

I'm really pleased to welcome Dr. Faiçal Miyara as our Chief Business Officer and Mr.

Jim Ziegler as our Chief Commercial Officer. Both bring deep experience directly relevant to the next stage of Ascentage's growth.

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

Thank you, Dr. Yang.

My name is Faiçal Miyara. I am the current Global Chief Business Officer at Ascentage.

I have a 20 years-plus in oncology business development, search and evaluation, and I also was involved in venture investing across leading pharmaceutical industry. I was in, as you see in the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen, as well as mid-sized biotech like Cullinan and IO Biotech.

I was also instrumental in the deal or the M&A that happened between Cullinan and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executive teams at IO Biotech and Ipsen.

When I was at Eli Lilly, I advanced Erbitux and Cyramza as a lead oncology products or antibodies, and co-initiated the Pfizer Center of Therapeutic Innovation. I'm very, very pleased to join this very, very good team at Ascentage.

We'll talk about our pipeline; it's a very, very outstanding. With that, I'll leave it to Jim to give you some information on the Chief Commercial Officer.

Thank you, Faouzi. Good morning, everyone.

I am also very pleased to join the Ascentage team. I've spent more than 25 years building and leading commercial organizations with broad experience in hematology, oncology, and specialty products across both large-cap and small-cap biopharmaceutical companies.

What attracted me to Ascentage is the opportunity to take a deep, late-stage hematology oncology portfolio with two already-approved products and help translate this clinical foundation into a global commercial organization. My immediate focus is on building the foundation for potential commercialization of our products, including commercial strategy, market access, and associated capabilities we will need as our registrational programs advance in the United States and other key markets.

I look forward to providing updates on our progress over time. I'll now turn the call back to Dajun.

Thank you both. Let's look at our R&D highlights.

Our development strategy is the engine for full global commercialization strategy. Two approved hematology assets 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 systemic therapy, including BTK inhibitors.

Actually, we conducted registrational 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 registrational 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 registrational trials for the global strategy is the GLORIOSA-4 in the frontline high-risk MDS, evaluates lisaftoclax in combination with azacitidine versus azacitidine alone.

This has been cleared by FDA, EMA, China CDE, and also PMDA in close to 20 countries. Let me also highlight a few key differentiations with two other currently on the market BCL-2 inhibitors.

As you can see, lisaftoclax was the only one designed with daily dose ramp-up in the beginning and the only one approved with only three dose strengths and five daily dose ramp-up plan, and then reach the dose of target dose 600 milligram and then continue. As you can see, the venetoclax was first approved about 10 years ago, has a five-week dose ramp-up.

The other one just approved, sonrotoclax, early this year, was a five-week dosing—I mean, the daily weekly dose ramp-up by the nine dose cohorts, okay, because sonrotoclax start with 1 milligram. Initially in the trials, was nine weeks.

I think they combined two into one week, each week they have do the ramp-up two times and then total nine dose levels to reach a target dose. I think that's really important for the patients with CLL/SLL, the convenience and also reduce the time of hospitalization.

Let's also look at the summary of favorable safety profiles and the better drug compatibility. We try to compare in the same setting, the same patient population, but also be clear, this is not head-to-head comparison.

If we look at the overall 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, lisaftoclax also much lower, and no drug-related death reported to date.

In the PK variability, I think that the other two are strong, the only 3A4 inhibitors. We show minimal fluctuation in plasma concentration compared to the other two.

I think that also no dose adjustment required compared to the other two, in terms of DDI issue. I think for the chronic dosing patient like many hematology malignancies, safety and tolerance and drug-drug interaction risk are important differentiation.

Let's also look at the key data in the U.S. trials, okay.

In the MDS, lisaftoclax with azacitidine in frontline produced overall response rate 80% and 50% in relapse/refractory MDS patient. More importantly, we have 40% CR rate, okay, and the time to response also really short.

Here we also highlight two representative real-world cases in high-risk MDS since it was launched last year in China. In the first case, a 71-year-old patient achieved CR after two cycles with rapid hematological recovery.

In the second case, a patient with poor response and failed venetoclax then achieved the CRi in 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 patient in U.S.

and Australia. This is not clinical data from China.

As we previously indicated, in the case of patient who failed venetoclax, which is truly unmet medical need globally, we still see a 31.8% overall response rate with no cases of tumor lysis syndrome. Same target, same pathway, and 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 BCL-xL upregulation. I think that explain partially why the same AML patient failed venetoclax, lisaftoclax can still achieve activity.

I think those reflects key differentiation in the downstream resistant profile and represent meaningful clinical opportunity. Of course, more importantly, with the better safety profile and the lower risk of DDI also provide more opportunity for combination.

In our case, combination with olverembatinib would overcome venetoclax resistance in AML. Turning to the second pillar of product strategy, olverembatinib.

I also want to highlight why we believe this can be a best-in-class third-generation BCR-ABL inhibitor to patients with CML in the second-line or late settings. This has already been approved and highly de-risked asset with several years of clinical and real-world use in China.

We receive a validation from Takeda as they hold the exclusive option to license olverembatinib outside Greater China and certain other territories. This was entered with Takeda about two years ago.

Globally, the most important study for the CML is POLARIS-2. Part A enroll chronic phase who has received at least two prior TKI, randomized olverembatinib against bosutinib.

This is cleared by FDA and the EMA. There's also Part B, which evaluate olverembatinib in patients with T315I mutation.

As bosutinib doesn't have activity, so that's the single-arm trial. Overall, you can see this is a difficult second-line patient population, which we believe olverembatinib can be most differentiated.

Besides the CML, olverembatinib also have strong activity in Ph-positive ALL. POLARIS-1 is also important.

This is our global phase 3 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 showed strong Part A data at ASH as oral presentation last year, and we continue to advance the global study. Let's look at the important bridging study led by Dr.

Elias Jabbour at MD Anderson. This actually was conducted four, five years ago.

Dr. Elias Jabbour, as is a leading investigator in CML and also Ph-positive ALL.

In this particular study, we enrolled 62 heavily pretreated CML CP patients. More than half have received at least four prior TKI, they're fourth or fifth-line, and half of them have received the ponatinib, and a third of them have T315I mutation.

I think with this really poor baseline patient population, we achieved the MMR as a single agent, 42.9% in ponatinib-resistant patients, 33% in asciminib-resistant patients, and more importantly, 27% in patients who failed both ponatinib and asciminib. Basically, those are the patients with no other options, but single-agent olverembatinib have pretty good efficacy.

I think this treatment, again, strength the overall differentiation and the clinical efficacy versus ponatinib and asciminib. Also, we have a pretty long-term safety profile.

In China, the longest patient have been using olverembatinib almost 10 years since October 2016. In this particular patient trial, the longest patient treated in the U.S.

is over three years with manageable safety profile. Let's turn to slide 16.

I want to share 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 and 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 remained only 10%.

I think that's a huge benefit for the patients in the late-line CML. Those patients actually have been treated with at least two TKI, some of those also with asciminib.

Olverembatinib delivered six months MMR rate 54%, and then even higher at 57% in 12 months. Those who didn't switch remained only low 20% response.

I think, as you can see, this 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 the benchmark is important because the new market change over the last two years.

I think at least two years ago the only competitive product we consider is the asciminib, but now there is two drug: TERN-701 and 1101 in the study in the U.S., okay. First, I think most important one, we're the only one have long-term evidence that other program doesn't yet have, as those are still in the phase 1 or early phase 2.

We have six years follow-up for patients who are in the second-line and 10 years for the first-line of the phase 1 trial. We're the only one have the comparative data set, okay.

Those are new requirement from FDA in terms of Project Optimus, 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 mutations. I think that those data clearly demonstrated olverembatinib as the potential drug of choice in the second-line of CML after patient who failed the most advanced available TKI.

I think I will show you a few more study in the control in more details on the next slide. Slide 18 is a real-world analysis of 69 blast crisis CML patient who went on transplant, and 26 was treated with olverembatinib and 43 with first and second-generation TKI.

The olverembatinib group entered transplant in deeper molecular remission: MMR rate 53.8% versus only 16%, and CMR rate 23% versus 4.7%. The olverembatinib also have more favorable survival outcome: one-year overall survival of 89% versus 71%, and no-relapse mortality 11% versus 23%.

These are the two separate patient cohorts in a retrospective real-world analysis, not a randomized comparison. Again, demonstrate important differentiation of olverembatinib in large patient population and hard-to-treat CML patients.

Let's also take a look at the combination strategy in the patient in the POLARIS-1 with low-intensity chemotherapy in frontline. I think the POLARIS-1 three key important differentiation the data.

One, this is frontline newly diagnosed Ph-positive ALL. In most cases around the world, chemotherapy still required because the aggressiveness nature of the Ph-positive ALL.

In the registrational trial design, we conduct the Part A with the low-intensity chemo. As you can see, this demonstrated 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.

This clearly demonstrate in the registrational trial setting, olverembatinib is the best among the current treatment option. We also try to enter the chemo-free registrational trial.

Currently, we have data from the oral report at the ASCO by Dr. Elias Jabbour from MD Anderson demonstrate that if combined with blinatumomab, we can achieve 80% MRD-negative rate and 91% CR/CRi.

We also demonstrate importantly in a pediatric R/R Ph-positive ALL patients. Actually, those data have been reported first time two years ago.

We continue to see benefit of safety and overall response. I think really impressively, we achieve 89% overall response rate after cycle two day 15, and all complete response in a oral chemo-free regimen.

I think this combination data is a key because this is two orally active agent chemo-free in the pediatric ALL setting. Moving on to the APG-115, another asset in our portfolio, small molecule targeting MDM2-p53.

It actually holds six FDA ODD and the two rare pediatric disease designation. This actually has been in our portfolio for a while, as there's no approved product yet globally targeting the MDM2-p53, as p53 is one of the most important tumor suppressor gene.

I think you do see some recent progress that Ipsen acquired Kartos' MDM2 inhibitor and with actually pretty decent $450 million upfront and up to $1.75 billion including milestones for a phase 3 program in myelofibrosis. I think there is probably potential for the MDM2-p53 inhibitor combined with JAK inhibitor in that actual trial as add-on strategy.

I think that data is encouraging, while also currently do that trial with MF patients. Again, this remain wholly owned by us.

In the ASCO, we present encouraging data for APG-115 in combination with lisaftoclax in the pediatric soft tissue sarcoma patients. Globally, pediatric rhabdomyosarcoma and other soft tissue sarcomas truly unmet medical need.

In that setting, we demonstrate good combination safety and impressive 23.5% response rate and also 70% disease control rate. I think those are encouraging data in the clinic demonstrate the orally active agent from Ascentage.

I think in the interest of time, I try to focus on mostly the key data. Here's a slide to show you that the cornerstone asset of BCL-2 inhibitor lisaftoclax combinability with three other targeted small agent, all are orally active.

I think we all know, as mentioned, that the main reason for BCL-2 resistance is the upregulation of MCL-1. We have demonstrated olverembatinib actually can indirectly downregulate MCL-1.

We not only have preclinical data, but now have clinical data to demonstrate that combination of the olverembatinib with lisaftoclax can show the synergy, more importantly not just CML or Ph-positive ALL, but the patient with 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're also moving into the DLBCL, AML, and MF.

Part of the MOA for this combination is the synthetic lethality. Again, we are the only company worldwide have all three assets wholly owned by Ascentage.

In the interest of time, I don't have much data to show, but I can tell you that our BTK degrader, APG3288, have advanced well in the phase 1 setting in both the U.S. and China across the B-cell malignancies who previously exposed BTK inhibitors.

I think we can stay tuned for the progress for both oncology and non-oncology indications with the BTK degrader. I think that's all the highlight of our R&D.

Let me turn the call over to our CFO, Dr. Veet Misra, for the review of our financial results.

Veet?

Great. Thank you, Dr.

Yang. Good morning, everyone.

Turning to our financial results, the first half of 2026 was another period of continued commercial growth and investment behind our global development programs. Total revenue was $44.5 million, compared to $32.6 million in the first half of 2025, representing an increase of $11.9 million or 29.3% on a constant exchange rate basis.

Product sales growth has been our main driver, as indicated by $41.6 million of product sales comprising our total revenues. During the first half, we continue to expand our commercial reach and invest behind both products, while maintaining a disciplined approach to managing operating expenses and advancing our global clinical programs.

Research and development expenses were $102.8 million, compared to $73.8 million in the first half of 2025, representing an increase of $29 million or 32% on a constant exchange basis. As planned, this was our expenditure and to execute on our high priority to advance enrollment in multiple global registration trials.

Selling and distribution expenses were $33.4 million, compared with $19.2 million in the first half of 2025, representing an increase of $14.2 million or 64.3% increase. This was driven by marketing and commercial investment behind our products.

Administration expenses were $17.5 million, compared to $13.9 million in the same period last year, primarily due to RSU expense. Turning to our balance sheet.

We're pleased to report cash balances were 270 point $279.4 million as of June 30th, 2026, as well as reaffirming our cash guidance runway through 2027, as we've said before. This funds us through multiple key registrational studies ongoing globally.

To emphasize, we are funding nine registrational programs and are currently taking initial steps to building a commercial organization in the U.S. and remain on target for investments required at the appropriate time to fulfill our global strategic objectives.

Thank you. With that, I'll turn back the call to Dajun for his closing remarks.

Dr. Yang?

Great. Thank you, Veet.

I think with all our R&D highlight and 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 this orally 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 registrational trials and reach to the NDA stage and build a strong commercialization team outside China as well, and to become a global player in the heme malignancies globally. I think that's all for the brief update with key data and financial results.

Thank you all for joining us and also our team. Then I think now we're open for the Q&A.

Sumedh?

Hey, guys. Thanks for taking our questions this morning.

Faouzi and James, welcome to the team. Just to start off in China, can you talk about how we should think about the NRDL listing for specifically lisaftoclax later this year?

Can you talk a little bit about what's the progress that you have been seeing in China, and how should we think about the next updates related to the NRDL listing? Then we have a couple follow-up.

Thank you.

Thank you, Brian. Really 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 R/R CLL/SLL patients in the registrational trial. That was a tough trial, but we demonstrated good safety, efficacy, and we clearly showed the differentiation versus venetoclax or sonrotoclax in terms of the only approved daily dose ramp-up with a clear safety profile and the lower risk of DDI.

I think if looking not just clinical data, by the NRDL reimbursement, less hospitalization, less risk, and also convenience are all important favorable factors for the NRDL consideration. I think currently, as update, we have passed the initial review.

We are on the final product list for the NRDL expert review right now. This year, the timeline is actually a little bit ahead of previous timeline.

Currently, there are two groups: NRDL experts, officials, and those health economics experts are conducting the meetings, reviews right now. We may call up to a meeting with experts later this month or early September.

Then we're very confident we will get NRDL coverage for these indications in China. The probably only concern we have or worry is working with the expert is the final price.

Of course, venetoclax already covered for different indication, AML in China, 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 reimbursement, but the ticket to enter the hospital. Majority hospital in China rely on the NRDL approval to enter the hospital in terms of prescription.

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%, 70%.

In certain regions, the NRDL coverage can up to 90%. I think that's a huge benefit to the patients in chronic leukemia setting.

Great. Maybe just also turning into your ongoing clinical studies.

Curious if you can talk about what's going on with POLARIS-1 and GLORIOSA trials, specifically how's enrollment looking like, and just any sense of how we should think about the timing of the next data readout and potential pathway to NDA filing? How should we think about the timing of those milestones?

I think for those questions, maybe we have our CMO, Dr. Zhai, on the call.

Maybe Dr. Zhai can give some answers first.

Dr. Zhai?

Sorry, Brian. Regarding GLORIOSA-4 study, right?

Sorry. I thought Justin [ph] somebody else's question.

Could you

please

repeat the question?

No problem. No, just curious how the enrollment is going in the global studies like POLARIS-1 and also the GLORIOSA studies for lisaftoclax.

How's the enrollment going? Do you have a better sense of when we're going to get the final data cut to file for the NDA?

Regarding all those global registrational trial, the team work very hard and try to complete the enrollment as soon as possible. It's still under the plan.

In particular, the GLORIOSA-4 study perhaps is under the radar, and everybody pay particular attention to that global registrational trial. Regarding GLORIOSA-2, GLORIOSA-3, Dajun actually already announced yesterday, we already complete the enrollment for GLORIOSA-2, waiting for the data mature.

GLORIOSA-3 also very close, and the remaining we plan to complete the enrollment either by the end of this year or the early next year.

Great. Thank you.

Maybe

let me add a few points to what Yifan said. We have said yesterday in the Hong Kong call that we complete the enrollment for the GLORIOSA-2, which is frontline CLL/SLL setting, combination with azacitidine and with fixed duration.

Of course, that one is not with FDA because the control arm is the chemoimmunotherapy. That's also over 400 patient enrollment demonstrate our capability in the clinical operation.

GLORIOSA-3 is the AML combo with Aza versus Aza alone. We're in the final stage to closing the enrollment.

The GLORIOSA-4, obviously, in the high-risk MDS, many people watching closely. I think a few key points also important to share.

One is this is the frontline, okay, the frontline patient with high-risk MDS in the trial design, similar to the VERONA, the combo with Aza versus Aza alone. This has been cleared by FDA, EMA, PMDA, and China.

Globally, not because VERONA failed, but also another BCL-2 inhibitor, sonrotoclax, is not on the MDS, not on the registrational trial. Globally, we are the only phase 3 registrational trial for the high-risk MDS.

There's no target drug approved in the high-risk MDS in the last 20 years. This is remained globally unmet medical need.

Enrollment is doing well because experts around the world in MDS are really enthusiastic, all want to help patients with high-risk MDS. Overall, I think to summarize, we anticipate, as we said before, the enrollment for GLORIOSA-4 and POLARIS-1, POLARIS-2 could complete by late this year or early next year.

The good problem to have, we're looking for potentially three NDA to file the second half next year.

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 a benchmark, internal benchmark, of efficacy early on? Thanks for taking our questions today.

I think you all know that the BTK as a target is really competitive, very crowd. There's many inhibitors, covalent, non-covalent, on the market.

Some are doing really well. The BTK degrader do have advantage, at least with some of the current up to even phase 3 data.

We conduct carefully preclinical data to show our drug, 3288, versus other two from Nurix or BeOne that have more better selectivity and stronger efficacy. That's, again, is in the preclinical setting.

Currently, I think in the phase 1, we moving along very well in terms of dose escalation for safety. More importantly, first, those are all BTK-exposed patients, okay?

Doesn't matter covalent or non-covalent. We want to still some response in those patient population first, right?

That's important. That's the key differentiation for the degrader.

Second, we probably will take some patient population, the indications, that currently BTK inhibitor is not really active and some also importantly combination with our BCL-2 inhibitor. I think one example in that setting may be the DLBCL.

Because so far the BTK inhibitor hasn't showed good activity as a single agent in that DLBCL setting. Of course, there are also a lot of data to combine with BCL-2 may have better read-out in this patient population.

Another potential one, but we don't have data to share yet, is in the non-oncology indication. I think there are many autoimmune indications could be benefit with the BTK degrader.

Great. Thank you, Dajun.

Congrats on the progress.

Thank you.

Hi team. Thanks for taking my questions.

Maybe if I could just start with the POLARIS-1 and POLARIS-2 trials, can you just provide us with an update in terms of when we can expect data from both studies?

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

Just address the same question. Let me repeat it.

Currently, we are very actively enroll patients and plan to complete the enrollment either by the end of this year or the early next year. Plan to submit the NDA next year.

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.

Of course, we already demonstrated very strong data in the MMR rate for this patient population, and we're confident on that. The key, of course, is to finish enrollment.

For the POLARIS-1, the filing of NDA with FDA is the three months MRD-negative CR rate. I think, again, the target enrollment is on track, and with this six months or three months endpoint for the NDA filing, we're looking for potential filing of those two NDAs second half next year.

Great. Maybe just follow up on a couple of questions.

For olverembatinib, when could we expect to see Takeda make a decision on its option on the license? That's 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 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 APG3288. Could we see first data at ASH this year?

Are you planning to evaluate also in the MS setting?

Maybe I'll answer your last question first. The 3288 is still ongoing in the phase 1 trial, U.S., China.

I think because this is dose escalation and the cutoff for the ASH already ended, we don't anticipate to present phase 1 data this year at the ASH. The progress are doing well.

Perhaps we can have some to share maybe EHA next year in terms of timing for the phase 1 data. Again, we are conducting several autoimmune indications demonstrate good preclinical activities.

Because the non-oncology trials in the phase 1 healthy volunteer, you do need the placebo control, right? That's where we are working with to getting IND filed for the non-oncology indications, including the MS.

That data will come from a little bit behind because making the placebo control. We do anticipate the IND to be filed soon with the autoimmune indications.

For your first question, I think the Takeda deal, as that we entered the global exclusive partnership option agreement two years ago, 2024. That is, again, exclusive global outside China and some territories.

For that, Takeda back two years ago paid $100 million upfront and $75 million equity investment. There's also a total up to $1.2 billion aggregate when they exercise the option and certain milestone payment.

Also the tiered royalty rate from 12% to start up to 19%. I think, globally, Takeda is a key player in the CML and ALL, after Novartis, obviously.

I think we do believe Takeda is important and global partner for commercialization olverembatinib. One of the main reason for the option agreement is, obviously, they have competitive product, ponatinib, and the potential antitrust issue.

Ponatinib patent will expire early next year. I think that's the key component in the option exercise.

Also, we do work closely since the option agreement signed with Takeda team. We are actually working closely together to advance all the enrollment and a lot of KOL reach and planning for the commercialization.

With Jim on board, we do looking forward working together ahead of the launch with 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're doing well in terms of getting the hospital covered. I think we do still have a second half time to report, but we are on the track currently bring the total commercial team about 300, and the goal is to build close to 400 commercial forces in China.

I think it's not just the number, 400 staff in the commercial team, but more importantly is to cover 80% of market potential with two product in China. I think that's where the 2,000 hospitals number we try to achieve.

We are on the track to achieve that with the expanding the commercial team and also the leadership both in U.S. and China.

Great. Thank you.

Thank you.

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 GLORIOSA-4? Then, just turning to olverembatinib, you highlight some of your competitors on slide 17, but if you could just provide some further detail or perspective on what you see are the biggest differences for your molecule versus those competitor agents on both efficacy as well as safety.

Thank you.

Really great question. First, based on the preclinical data, our drug is probably among all the TKIs or all 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 gatekeeper mutation differentiate those in terms of third-generation BCR-ABL inhibitor.

On top of that, there's also the more than one mutation called the compound mutation in the same cell, okay? Currently, asciminib and also those TERN-701 or 1101 do not have those strong data.

Olverembatinib is the most potent one and also most active against wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of late-line CML patients.

Currently, even though asciminib have approved label with only U.S. to treat the patient with T315I mutation, but they need a five-time dose, right?

Five-time dose and also in U.S. that's five times the cost, almost $1 million.

I think in the late-line CML patients with mutations, we do show probably the most important one, okay? And 1101 or TERN-701, now with Merck, do not have those data, and they are also mostly in the early phase 1 or 2.

In the U.S., because of Project Optimus, we have those data four, five years ago with MD Anderson that we have patient basically unmet medical need, right? Patient who failed both ponatinib and asciminib are the patient with no other treatment options.

Because the Project Optimus, FDA do not allow the single-agent, single-arm, pivotal phase 2 trials for the registration. That's why we have to conduct the RCT.

We have to have the control arm like bosutinib. I think none of those competitor products have those data or registration trial agreement with FDA yet.

In the real world, the consensus among the CML experts community is you want to give the best BCR-ABL inhibitor to patient failed after first-line early, right? You don't want to wait after four or five line.

You want to give the strong one, the CML patient who achieve deep response, like MMR, MRD, negative CR or the MR4 or DMR 4.5. Patient who can achieve deep 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's important. That's why we have a second-line data, we have the real-world data, prospective comparative study to demonstrate the olverembatinib could be the choice of patient who failed the frontline.

Doesn't matter it's a TKI or asciminib or any other allosteric inhibitor. That's the goal.

That's the key differentiation we have been showing presented with clinical data.

Thank you. Appreciate it.

Thank you.

Great. Good morning, and thank you, Ascentage team, for taking my question and congrats on the progress.

My question just to start is just on lisaftoclax. Certainly, when it comes to the commercial trajectory over this year, could you just comment about how that's perhaps changed since Sonrotoclax has entered the market?

Are these two drugs competing directly, or is lisaftoclax certainly as approved in the post-BTK monotherapy setting just producing a more of a meaningfully different initial patient mix? Maybe just comment a bit on the five-day ramp-up as you've mentioned, how that's perhaps translating to more measurable real-world advantages in China?

Thank you. A

great question. Overall, BCL-2 is a really tough target, right?

We have been working on that in the lab for 30 years, clinically for 21 years, advanced three products into clinic, but only lisaftoclax made to the market. Again, we always compare with venetoclax, and that daily dose ramp-up was a key differentiation in the beginning.

We're the only one approved to go to the clinical trial and approve the label with the clinical data. I think in the CLL/SLL patients, some of the early risk was in the tumor lysis syndrome.

That's why venetoclax and also sonrotoclax went to this weekly dose ramp-up, right, and require hospitalization and close monitoring because tumor lysis risk. On the other hand, because venetoclax already on the market, same with sonrotoclax now, the differentiation in the chronic dosing patient like 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 half-life that translate into better safety profile, less neutropenia, thrombocytopenia, and also much less infection. Some of the hematology malignancy patients in the clinic presented first is actually the infection, like high-risk MDS, right?

Then they found out actually the bone marrow is the one has the cancer cells. The patient with high risk of infection, it's important you have lower risk of DDI drug to combine with, right?

Not just combine with azacitidine, standard of care for high-risk MDS right now, but also in some case of marrow disease, especially 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.

They compare even with sonrotoclax now on the market you see from the label that they even have higher risk of DDI than venetoclax, okay? I think the differentiation in terms of daily dose ramp-up, convenience, better safety profile, tolerance, and lower risk of DDI is important for this chronic dosing leukemia patients.

I think that those are the one remain confident will show the benefit to the patients globally once it reached to the market.

That's really helpful. Thank you, Dr.

Yang. Maybe just a question on the pipeline.

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

Thank you.

To be honest, it's hard to say which one, it's all data-driven, right? To your question, we're really 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 challenge 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 2 setting, multiple tumor indications, but we haven't really see the signal for the registration path before.

Currently, we do see now with combination with the BCL-2 inhibitor clinical benefit and the MOA of synthetic lethality. On the other hand, even though it's from the competitor product, the Kartos' compound also entered the phase 3 registration trial with the add-on strategy of JAK inhibitor in MF.

Obviously, it's encouraging to see Ipsen entered the acquisition with potentially $1.75 billion. I think there is potential maybe at the end of the tunnel to see the finally MDM2-p53 inhibitor may enter the market or registration path.

For your question, I think among the pipeline, we have five of them right now. Each one of them have unique different strengths 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 1 trial in lymphoma setting.

We are very excited to show this data at the upcoming ASH, that's already submitted. For the EED inhibitor, there's also potential in prostate cancer, in some other settings of solid tumor.

I think there's a lot of potential in the EED. We are the first one in China, globally the second in oncology setting.

I think there's 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 currently, in addition to the two approved product in China, globally four registration trial clearly the focus, right? We want to getting the first NDA filed with FDA those two product.

As you can see, on the five clinical-stage asset, at least those three I mentioned clearly show the leading advantage globally with clearly clinical data. I think those are still early, not reaching the registration trial yet, I think we have sufficient resources in terms of budget and the clinical team to advance those trials.

Again, which one is favor, it's hard to say, it's all data-driven, but I think all these three do have really exciting data and a path to registration.

Maybe just to add to that, as it relates to our presence in China, our legacy in China, we're 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. I think that's important to keep in mind about us.

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

Yes, team. Thanks for taking our questions and appreciate the helpful detail.

A couple of quick questions on lisaftoclax. I think you're talking about ven failure patients development being explored.

Could you maybe just touch on how quickly you can generate data there? What does the patient pool look like?

Then on GLORIOSA-4, if you could maybe comment on your expectation for CR rate and TLS, and how maybe the interim OS analysis would be handled in the study if there's anything early built in there? Then I have a follow-up question on POLARIS.

The first question, I think maybe Yifan can answer.

Great question. Yes, based on our preclinical data, we have reported using lisaftoclax in combination with olverembatinib able to overcome venetoclax resistance, which we have previously reported at the AACR.

We also use very preliminary data we submit to this year ASH, and when the data mature, we have data demonstrate that the combo able to overcome the venetoclax resistance. The data is preliminary, but very exciting.

We submit the abstract to ASH. That's address your question.

We in the process in globally, including in China or outside China in U.S., and we try our best effort try to enroll more venetoclax treatment-failed patient population using different strategy based on the known resistant mechanism to target this ven-resistant AML population either using the combo or our other compound, APG-1252. To address your question, GLORIOSA-4 study, as we mentioned, because this is a double-blind randomized study, we cannot analyze the data early is 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 because based on the current design and the dual primary endpoint, we are able to submit the NDA and using the CR rate as the primary endpoint, and then continue to mature the OS data and sometimes next year.

Thank you. I appreciate the detail.

Then on a similar kind of question on POLARIS-2, on the treatment effect for 24-week MMR rate, if you could maybe just comment on what you've powered the study for? I was also curious because your MMR rates grow with time, 48, 96 weeks.

How are you handling crossover from control arm ponatinib there? Do they have option to get your drug, or they're moving on to other trials, and what sort of longer-term efficacy we can get there?

Very good question. 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 investigation arm.

Later on, we try again to request, and FDA finally give the green light allow those patient failed from the control arm crossover to olverembatinib. That will make the study more attractive.

Number one. Number two, regarding the endpoints, currently we use the 24 weeks, at the 24 weeks MMR rate as the primary endpoints.

The basic this study design is the power enough and double the MMR rate compared to control arm.

Also just add one, the design of the POLARIS-2 in terms of because of the Project Optimus, right, you have to do the RCT, and you have to have a control arm. In that particular setting, FDA did agree this is a 2-to-1 ratio, and also allow the crossover, okay?

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 48 patients, okay? I think the total POLARIS-2 is 333 patients and enroll well, and then the six months MMR rate for the initial filing of the NDA with FDA.

Awesome. Thank you.

Last one for Veet, if I may. Just if you could comment, Veet, on your OpEx trajectory, and if you're getting to peak.

I know you have a lot of registration studies. Just maybe comment on where we are with the R&D spend and what you expect to see with the pipeline over the next 12 months.

Thanks for taking our questions.

Great question, Mayank. As I said, we reaffirmed our cash runway, and we're happy that we've been adhering to our forecasted spending, given the scale of our studies, globally, multiple countries.

We're 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 discussed that.

I think, as it relates to the expenses for the studies, we're now, given we're at the late stages of enrollment, we're now kind of at the peak as it relates to OpEx spend. All that is going as planned and expected.

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

Got it. Thank you, Veet.

Of course.

Thanks for taking the questions. Congrats on the progress, guys.

Maybe I wanted to drill down a little bit further on the balance sheet question. If you could talk a bit about a little further about capital allocation, because you guys do have a fairly hefty burn rate, and even with the Takeda opt-in, you're going to require a lot of capital in highly competitive markets, even with differentiated products.

You do have entrenched competition. 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?

Maybe I can start. Or go ahead, Dr.

Yang, and then I can... No,

no, Veet, you go ahead.

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 wanted to establish. What we have done is, with the dual listing steps we've taken is allow ourselves, we believe, within as reasonable as possible, maximal flexibility and optionality in terms of various alternatives to raising capital.

Obviously, when it comes to commercialization, that requires expansion capital. 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 Faouzi on board, the optionality as it relates to potential partnerships when it makes sense as well. We are not in a pressure for one particular path, which is exactly where we want to be at this point.

I think fully agree. Just add one more point that our current cash runway, as we stated before consistently, can support our R&D plan through the end of 2027.

More importantly, with nine registrational trial and four global cleared by FDA and the EMA, majority of this enrollment already done, as that's why you see the first six months, we have our R&D expense, more than 30% increase, primarily due to this heavy enrollment. The good news is that the mostly part of the costs is already at least more than halfway done, right?

Of course, we remain open, flexible for many options for the fundraising, and also partnership, other source of income, on top of our positive continue grow revenue with two product sales in China. I think we're really unique, it's not just because we have legacy and resources in China, but also steady growing revenue income from China and looking forward for the global commercialization and revenue as well.

Great. Thanks for taking the questions.

Thank you, Mike.

Thank you all for joining us. I think this interim report, again, position us well to be the global player in the heme malignancies.

More importantly, we are advanced well in terms of all the key registrational trials, and then with the target to complete them by the end of year or early next year. More importantly, we're in the position, if you look at some of the competitor or the really excellent biotech company this time last year, okay, I told my team and many investors, Ascentage will be a different company by the time next year, okay?

We're looking forward to your support and looking forward to working with our team, investors, and the HCP globally to make those novel, safe, efficacious drug into the global market to help patients with unmet medical need globally. Thank you all for your attention and support.