Thank you, operator. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions.

These statements involve risks and uncertainties, and actual results may differ materially. For a full discussion of these risks, please refer to our filings and disclosures.

On today's call, I am joined by Dr. Dajun Yang, Chairman and CEO, who will provide an overview of recent developments and 2025 annual performance, as well as Dr.

Veet Misra, CFO, who will go through the financial highlights. The presentation will then be followed by a Q&A session.

During this Q&A session, the team will be joined by Dr. Yifan Zhai, Chief Medical Officer; Dr.

Shaomeng Wang, Co-Founder, Chief Scientific Advisor; Dr. Zhichao Si, Head of Commercial.

I will now turn the call over to Dr. Yang.

Thank you. Good morning.

I'm Dajun Yang, Chairman and CEO of the company. Today, I'm very happy to present our 2025 full-year financial results and a corporate update.

I will have the following agenda: business update, R&D highlights, financial results, and a Q&A session. First, on the business update, 2025 was a breakout year for Ascentage.

First, we have achieved excellent total revenue over 90% growth and total $82.1 million. Our year-end cash balance is about $353.2 million, cash runway through 2027.

I think in 2025, we are the first dual-listed biopharma company on NASDAQ following our Hong Kong Stock Exchange listing 2019. We successfully raised approximately $322.6 million through IPO and follow-on offering.

It's the first time we have a dual commercial product. Based on that, we established a fully functional, large-scale, and fast-growing commercial team, currently close to 300 staff.

We are on the path to be a premium global commercial hematology-oncology company. We also achieved many major R&D milestones.

These are the following examples. First, lisaftoclax approval as global first single-agent BCL-2 inhibitor after BTK treatment in CLL and SLL.

GLORIOSA-4 Phase III registrational trial received clearance globally, including FDA, EMA, and CDE. This is a truly unique opportunity, as we are the global Phase III registrational trial in high-risk MDS, the only one in that Phase III registrational stage.

POLARIS-1 for the Ph-positive ALL, the Phase III registrational trial also received clearance globally, including FDA, EMA, and CDE. Part 1 data also reported at the ASH, demonstrate strong 64% MRD-negative CR rate in the first-line Ph-positive ALL.

Olverembatinib granted the breakthrough designation for the first-line treatment of Ph-positive ALL by CDE. We're also really proud to have FDA and CDE IND clearance for our novel BTK degrader, APG3288.

Both lisaftoclax and olverembatinib entered 2025 CSCO guidelines. Multiple oral presentations at ASCO and ASH 2025.

We continue to lead in the global innovation for many of our products, including multiple presentations at ASH, AACR, ASCO, EHA, and other conferences. Also we published on many peer-reviewed top journals.

I think here is our summary of world-class, innovative, highly de-risked, and super late-stage pipeline. Here are the list of seven novel compounds.

The first two, olverembatinib as novel third-generation BCR-ABL inhibitor, and lisaftoclax as the novel BCL-2 selective inhibitor. Both have been marketed in China and also entered four global registrational trials cleared by FDA, EMA, and total we actually have nine registrational trials for multiple indications.

We also have several novel, potentially first-in-class compound targeting such as FAK, ALK, ROS1 triple kinase, and MDM2-p53, the dual BCL-2/XL, and the PRC2 third-generation like EED inhibitor. More importantly, we have newly cleared Phase I novel BTK degrader, APG3288.

All of these are running the trials in US and China and multiple countries. Many focus on hematology-oncology, but also have a potential and also in clinical-stage testing indications such as anemia.

We have build a really large commercial scale in China with dual product approved. Especially for our BCL-2 selective inhibitor, lisaftoclax was ahead of our schedule last year, and with two commercial product, we have build over 270 by the year-end commercial team, covered the 1,500 hospitals and more than 800 DTP pharmacies.

I think our dual-engine strategy worked well, as you can see our last year commercial revenue. I think that is transition for Ascentage from being rely on the investment, investors, and also BD income to the last year 100% sales of the commercial-stage product.

I think that's really important transition for the company to be able self-sustained with our own revenue to support our own R&D program. If you look at just olverembatinib alone, we have strong sales following full NRDL listing covering CML with, without mutation.

If you look at the total sales reaching $62.2 million, that represent 81% year-over-year growth. We continue cover more hospitals, DTP pharmacy, and also broader reach to the tier-1 hospitals.

With the full NRDL coverage and also translating into very long DOT that will support a sustained growth as the patient continue to use our drug over a long time. If you look at the lisaftoclax, first, this July approval was ahead of schedule, and we built a very fast and full functional commercial team dedicated to lisaftoclax.

The streamlined go-to-market strategy using the national commercial infrastructure really helped us to rapidly expand the sales force and the hospital coverage. Just the first 5 months, we have reached more than $10 million US sales.

This is, I think, is among top at least in the hematology-oncology product sales in the first couple months in China. Then let's go to the R&D highlights.

First, let's look at our lisaftoclax. It's actively advancing its global Phase III registrational trials.

First, our approval as a single agent for CLL/SLL after BTK inhibitor is really represented the first label for the BCL-2 selective inhibitor. As venetoclax was approved 2016, and continually the only single agent was limited to the 17p delete CLL and SLL.

The other CLL/SLL is all combination with the CD20 antibodies. Our GLORIOSA, GLORIOSA-2, and GLORIOSA-3 also received FDA, EMA, and CDE clearance.

More importantly, I think the GLORIOSA-4 is the first-line high-risk MDS in combination with AZA or without AZA, azacitidine, control arm. Both received FDA, EMA, and CDE clearance.

We'll continue pushing forward all these important global Phase III registrational trials. I want to share a few important clinical data with you.

First, with the single-agent approval based on the CC-201 registrational study, those patients actually have much poor baseline characteristics. First, the CDE actually give us very high bar about 4, 5 years ago, required all these CLL/SLL patients have to fail both BTK and CD20 antibody-based therapy.

Many of them have high-risk complex karyotype, and also many have multiple mutations. We achieved a really good efficacy as a single agent and demonstrated a favorable safety profile.

If you look at another key data in the AML and MDS, actually this is primarily US and Australia data with leading PI from the US, and this is actually has presented both at ASCO and ASH. If you look at our ORR as combination with AZA in the newly diagnosed AML patient, we achieved ORR 83%.

More importantly, in some cases, about 22 patients who are failed venetoclax, we also achieved 32% ORR. In the MDS, we have in the newly diagnosed 80%, and in the second-line R/R MDS, we have 50% ORR.

I think based on those excellent data and many other clinical data, FDA gives us clearance to conduct global Phase III registrational trial as the first-line for the high-risk MDS, and this has been cleared by FDA, EMA, and CDE, actually among close to 20 countries' regulatory agencies. We are active enroll patients in US, Europe, China, and throughout the world.

If successfully carry out, lisaftoclax can become the first BCL-2 inhibitor for the treatment of first-line high-risk MDS. This is really a global unmet medical need, as there's no target therapy approved in the last 20 years, and current therapy have much poor efficacy, and 5-year survival rate for high-risk patients is only about 16% to 24%.

We are also really proud this global effort is leading by Dr. Guillermo Garcia-Manero from MD Anderson and Dr.

Xiaojun Huang from Peking University People's Hospital and many, many excellent expert and PIs for MDS around the world. Based on the public information, we want to highlight few key difference of our drug versus venetoclax or sonrotoclax.

If we look at based on the similar registrational trial study, again this is not a head-to-head comparison, but a really similar patient population, including those in China. If you look at the SAE incidences, it's much higher for venetoclax or sonrotoclax, and infection rate also significantly higher.

That's consistent with clinical observation that lisaftoclax have better safety profile, better tolerance, and more importantly, we have better drug compatibility. CLL/SLL patients often are elderly and immunocompromised with frequent infections.

Commonly used antifungal drugs are strong 3A4 inhibitors but does not affect our lisaftoclax PK. If you look at the PK variability in combination with some strong 3A4 inhibitors, I think the impact for lisaftoclax is minimal.

Other two drugs either need about 8 times or 11 times need to be adjusted dose if they're combining those. That will strongly affect clinical combination studies.

Also in look at the P-gp or BCRP substrates or inhibitors, lisaftoclax is probably the one have minimal risk in those combination studies. No need to adjust dose with like many BTK inhibitors.

I think those are really unique advantage for lisaftoclax as the BCL-2 selective inhibitor. I also want to highlight a few important progress made and the summary here for olverembatinib.

Olverembatinib is approved with full coverage by NRDL. We see excellent commercial coverage and revenue growth last year.

Globally, we are conducting POLARIS-2 for the CML, and this single-agent study in RCT with the bosutinib as a control arm also received FDA, EMA, CDE, and the PMDA clearance. We are actively pursuing advancing the global enrollment.

POLARIS-1 is really important. This is the first time we got a clearance last year for the first-line Ph-positive ALL.

This also cleared by FDA, EMA, and CDE in China with the breakthrough designation. Part 1 of this trial, the same trial design, data was presented at ASH.

You can see the data from next couple slides. First, in the Part A of the Phase III registrational trial, in combination with low-intensity chemo as the first-line, we have achieved 64% MRD-negative CR rate.

This is almost double the same patient population for the ponatinib, which only have 34.4% MRD-negative CR rate. This actually is among all the BCR-ABL inhibitors the best one.

We actually almost double the best BCR-ABL inhibitor for the same patient population, and also demonstrate really well safety profile. Another data is looking the potential second-line treatment for the CML-CP patients.

This also again presented at ASH last year. We can achieve more than 50% I mean 70% CCyR rate, more than 40% MMR rate, and also have a really durable, sustained response.

Another important is in the blast crisis of the CML. I think we demonstrate in more than 64 patients with blast phase and also some serious cytogenetic abnormalities and complex karyotypes.

Those patients did very well and also into the sustained remission with improved survival and much reduced non-relapse mortalities. Another potential treatment is really for the combination with our olverembatinib, and in this case, it's actually in the pediatric patient population that in the first-line regimen in the Ph-positive ALL demonstrated really excellent efficacy and the safety profile.

I think this would be really important for some of the patients to receive the chemo-free and the two orally active agent with a long-term benefit. Olverembatinib as a multikinase inhibitor also demonstrate clinical benefit for some rare hematological malignancies, such as this really hard to treat myeloid/lymphoid neoplasm with FGFR rearrangement.

This actually take a while to recruit those patients, but most of them achieved an excellent response clinically. We continue to push our pipeline.

In the interest of time, we only show one example as our novel BTK degrader, APG3288. This actually we received almost the same time clearance by FDA and CDE.

Based on the preclinical data, I think we also did a comparison with B1 or Nurix BTK degrader, demonstrate good selectivity and potency. We'll push forward this compound in US and China for multiple indications.

I think in summary, lisaftoclax as a really safe and potent BCL-2 selective inhibitor, some refer BCL-2 inhibitor as a small molecule of PD-1. That really means it has multiple indications and also opportunity for multiple combinations.

I think more importantly, we are probably globally the only company has not just the BCL-2 selective inhibitor, but also olverembatinib, representing the best third-generation BCR-ABL inhibitor, and the MDM2-p53 inhibitor, and also the novel, new BTK protein degrader. As you can see, each one of these is a single agent or in combination have potential to treat a multiple B-cell malignancies, among many hematological malignancies.

Lastly, I think I will turn the financial results to our CFO, Veet. Veet,

please

go to the slide number 28. The [unclear]

yeah. Thank you so much.

So 2025 was a successful year for us as we established our commercial strength with now two approved novel oncology products. In 2025, our total revenue was US$82.1 million, excluding payments from Takeda as a comparison to last year, which represents a year-over-year increase of 90% on a constant exchange rate basis.

This high revenue growth rate was driven by our aforementioned dual-engine commercialization strategy, as articulated by Dr. Yang, and centered on olverembatinib and lisaftoclax.

Turning to olverembatinib and lisaftoclax individually, olverembatinib sales of US$62.2 million represents year-over-year growth of 81%. Sales of this product reflected first full year of NRDL inclusion, hospital and DTP market penetration, which drove increased volume uptake.

Turning to lisaftoclax, which was approved in July 2025, first 5-month sales of $10.1 million was attributed to our established commercial infrastructure that was built to scale ahead of approval and is anticipated to drive strong market penetration going forward. At the same time, we continue to adhere to a disciplined approach to efficiently manage and prioritize our operating expenses to support accelerated commercial activity, as well as our ongoing clinical studies, including global registrational trials.

As you can see, our year-over-year increase in R&D expense from US$130 million to $163 million year-over-year, which is tied to advancing ongoing global pivotal studies, represents a 20.1% growth rate to support trials that are expanding and moving forward. In addition, the increase in SG&A expenses, sales and distribution in 2025 from US$27 million to $51 million, was primarily driven for sales force expansion ahead of commercial launch of lisaftoclax, which is an efficient use of capital.

As you can see, the increase in these two major line expense items compared to our revenue growth demonstrates our disciplined approach. Finally, in terms of our cash balance, our 2025 year-end cash balance of US$353.2 million compared to US$172.8 million reported year-end 2024 is a result of product sales and two completed successful financings in 2025: our January 2025 NASDAQ IPO, as well as our follow-on offering in July 2025 on the heels of lisaftoclax approval, raising combined proceeds of US$322.6 million.

As a result, this allows us to maintain our estimate of cash runway through 2027, as we've stated before, which importantly funds us through multiple key registrational studies that are being conducted globally and execution of our overall commercialization strategy. Thank you.

I'll now turn it back to you, Dr. Yang.

Thank you, Veet. I also want to present our clinical catalysts and the milestone for 2026.

On the clinical development side, our major focus will be advance enrollment for the GLORIOSA and the GLORIOSA-4 registrational trial and also advance enrollment for olverembatinib in terms of POLARIS-2 trial and also POLARIS-1 trial. I think as we mentioned earlier with our team, I think the key word for 2026 is really the enrollment, enrollment, and enrollment.

I think we'll do our best to achieve and complete enrollment and then be able to file NDA in 2027. We'll continue to push the degrader, APG3288, global Phase I study in terms of safety, tolerability, PK, and the potential efficacy data.

Also advance our EED inhibitor, APG-5918, in both oncology and anemia. Of course, we'll continue to push other active compounds in clinical study in the US and China as well.

I think the major in terms of milestone for the clinical development are those highlighted here. On the commercial front, we will continue drive the sales growth for olverembatinib and also lisaftoclax to the tier-1 hospitals and more pharmacies.

For lisaftoclax, we will do our best for the benefit of patients, especially CLL/SLL, together to the NRDL coverage in China in 2026. I think the key driver for Ascentage to be a global player in hematology-oncology is really driven by the two novel and potentially best-in-class compound, olverembatinib and lisaftoclax.

We also have a dedicated hematology-oncology sales force, not just based on the really rapid scale in China, but more importantly, our global strategy positioning and the branding. I think with our world-class clinical execution and the proven track record of translating the clinical development into the novel commercial product and advance our best-in-class potential therapeutics in global registrational studies, I think with the dedication and effort from all our team and also our collaborators and PIs around the world, we'll really moving our pipeline to addressing the global unmet medical need, making Ascentage to become the global leader in this therapeutic areas.

Lastly, I think with the patient-centric innovation and global breakthrough therapies, and with currently seven active compounds, small-molecule drugs in active clinical trials, addressing multiple hematology malignancies from the CML, ALL to CLL, AML, MDS, multiple myeloma, and potentially some of the lymphomas and the anemias. Hopefully, with all your support, we can make 2026 another successful year for Ascentage.

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

Thank you.

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

Dajun and Veet, good to chat with you. Maybe just first, Dr.

Yang, you talk about how this year is really about enrollment, enrollment, enrollment. Can you give us a bit more color on where you are in terms of enrollment for your registrational studies, especially the GLORIOSA-4 study in MDS with lisaftoclax and also the POLARIS-1 study in Ph-positive ALL?

Related to those indications, how should we think about the next data milestones at the upcoming medical conferences later this year? Thanks.

Thank you, Brian. Really excellent question.

I think let me maybe addressing into two part. First, for the GLORIOSA-4, high-risk MDS, we are really happy to see this Phase III registrational trial protocol received clearance by not just FDA, EMA, CDE, and also among close to 20 countries' regulatory agency.

This is the first-line treatment for the treatment-naive newly diagnosed high-risk MDS. More importantly, this is now really the only Phase III registrational trial in the high-risk MDS globally.

We're really happy to receive the support from the PIs around the world, and they're really enthusiastic for this clinical trial to help patients globally with MDS. With the POLARIS-1, this is the first-line Ph-positive ALL.

As we also presented the Part 1 of the same protocol data at the ASH. The 3 months MRD-negative rate CR is 64%, almost double the ponatinib on the same patient population, about only 34%.

I think those two registrational trials are both for the first-line treatment, which will actually much easier enroll than some of the late-line protocols. Of course, also have a huge potential market return.

With those two first-line treatment, and you can see MDS, we are the only one front-runner in the Phase III registrational trial globally, there's almost no competition there. The POLARIS-1 is first-line for the Ph-positive ALL, also with excellent data, potentially the best-in-class for the Ph-positive ALL patient population.

I think the enrollment are doing well, and even though both only initiated late last year. We see so far the really excellent enrollment and really strong support from the healthcare providers around the world.

The POLARIS-1 only requires 3 months MRD-negative CR rate as a primary endpoint. Also we have a strong support from FDA and all the regulatory agencies to support the protocol of the GLORIOSA-4.

I think overall we will do our best to achieve complete enrollment. With the current timeline and the primary endpoint, we anticipate do the best we can and then to be able release the top-line data or complete enrollment, and then be able to file NDA in 2027.

Got it. Maybe just one more.

Just how do you think about the commercial growth opportunities for both olverembatinib and lisaftoclax franchise this year in China? Are there any specific drivers that you see today that your sales team is fully leaning on?

Then perhaps we actually have a follow-up after this. Thank you.

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

Yeah. Okay.

Thank you for question. If you look at the actual driver of growth in 2025 in China, I believe there are several key drivers.

If you look at olverembatinib and which really benefit for the broader reimbursement support affordability after NRDL inclusion, right, which Dr. Yang also mentioned, and also very strong patient affordability improvement.

Second, if you look at our annual report, we continue to expand the hospital and D2C pharmacy access with more than 800 hospitals and D2C pharmacy, which is significantly improved the accessibility by the year-end, which also includes more than 355 hospital with formulary access. Hospital listing is very important in China market.

Third, I believe if you look at the lisaftoclax, which was approved in China, and since July, and we got sales for 5 months. Lisaftoclax really give us a second growth engine after launch and generating more than 70 million RMB in the first 5 years on the market.

Fourth, I think we scaled our commercial organization. Dr.

Yang and Dr. Veet both mentioned, we scaled up our commercial organization meaningfully.

Our team actually almost tripled compared to 2025 compared to 2025 compared to 2024. This commercialization team grew into more than 270 people and covering more than 1,500 hospitals nationwide.

I believe that's the key driver for last year's commercial growth. Thank you.

Great. Then maybe just lastly, just want to touch on your BTK degrader here.

Dr. Yang, can you first give us a better sense of how you see differentiation compared to other BTK degrader that's out there?

Then as you think about your Phase I study, what will be good to see from this initial Phase I?

Brian, really good question. For the first maybe clinical part, I will have our Chief Medical Officer, Dr.

Zhai, to address. Yifan, can you hear?

If not, maybe let me try to answer your question. First, we have conduct very thorough of course it's currently preclinical data to compare our BTK degrader with B1 or Nurix.

I think based on this comparison, we selected our candidate compound moving to the Phase I. Based on the preclinical data at least, we show better selectivity and also more potency.

That's number one. Number two, I think as the BTK is validated target, the BTK degrader can take care many of the BTK inhibitors, covalent, noncovalent, mutation or not.

Basically have broad efficacy in the oncology space. I think most unique for Ascentage, once we go through the Phase I typical safety, tolerability, PK, and some signal of efficacy with the potential RP2D, we probably move very quickly into the potential single-agent indications for the fast-to-market approach.

The second part I think unique to Ascentage that we have a really excellent BCL-2 selective inhibitor. The combination of a BTK inhibitor or degrader and a BCL-2 inhibitor could really offer some of the hard-to-treat patients benefit.

In the case of the CLL/SLL, at least with the fixed duration, it's really a potential even in some case clinical cure. That means there's no progression after 5 years stop the treatment.

I think that will also offer additional benefit, especially for the young patient with the CLL/SLL. In combination with the BCL-2 maybe also can treat some hard-to-treat like DLBCL.

I think thirdly, I think also at this part of our moving forward strategy potential to maximize return, is that there are also many non-oncology indications for the BTK degrader in like autoimmune diseases. I think with all those three reasons, we are really looking forward to full speed to push this novel BTK degrader into the clinical development and many other potential combinations and the indications.

Great. Thanks for the color and thanks for taking our questions.

Thank you.

Hi. Thanks for taking my questions.

Maybe to start for olverembatinib, what is your market share in China versus asciminib and ponatinib? Which CML patients are you seeing the most adoption?

Then I guess, for second-half 2025, sales grew by about 7% versus first-half '25. What can we expect for the growth rate for olverembatinib in 2026?

Thank you.

Really good question. The 2025 was the first year for the NRDL coverage.

Especially for the with, without mutation. The patient population compare our first approved indication with T315I mutation only, we the patient population more than tripled.

That's number one. The NRDL coverage for this chronic patient is really significant, as they can averaging nationwide can reduce at least 70% the payment.

In certain better, economy the countries, I mean the province, the reduction payment can be reduced by 90%. That's really significant as this patient is taking the drug, a long time, right?

Really good a long DOT. The NRDL coverage in China for the CML patient, we see a really benefit important benefit.

The patient population in China as other late-line treatment, like you mentioned asciminib or ponatinib, both were only approved last year. Okay.

About, they don't have any establishment or the data from China. We also have, last 3, 4 years market use, even though for small dedicated mutation patient population.

Overall, the physicians and the patients are really well-educated, positioned. Once get into the full NRDL coverage.

For the both asciminib and ponatinib, they were not under NRDL coverage. Okay.

That's also limit the use of those two drug only got approved a year ago. They're not really a much sales affordability for those not under NRDL-covered the asciminib or ponatinib in China.

The moving forward for 2026, we see the benefit of NRDL will continue, as the price is good for 2 years. If we just look a little bit the next year ahead of NRDL renew, we're also really confident as the new policy from the NRDL is to maximize the support for the novel agent and also those unmet medical need.

I think olverembatinib is one of the examples falling into the category with the strong support by the NRDL. Also we currently the another important indication also really high prevalence disease is Ph-positive ALL.

In the real world, we do have many Ph-positive ALL patients benefit by the olverembatinib. The same time because they are not officially into the NRDL coverage, currently in those patient population, we still want to finish our registrational trial, be able to the got into the NRDL.

The moving forward, I think there's continue expansion and growth of the revenue for olverembatinib in China, both CML and the Ph-positive ALL.

Thank you for that, Dr. Yang.

Maybe just a follow-up. Clearly, there's a lot of focus on the CML treatment landscape, especially yesterday Merck announced acquisition of Curis for $6.7 billion.

How do you think olverembatinib would fit into the emerging treatment landscape in the US for CML? Then second question, which of your global pivotal trials across both olverembatinib and lisaftoclax can we expect to see data in 2027?

Thank you.

Great. Really excellent question.

Actually we are all very excited to see the acquisition of the Curis by Merck with obviously really good price, $6.7 billion in all cash. I think the positive side is really that means the CML market globally is actually quite big, right?

To be honest, a couple years ago when we were developing olverembatinib, there are some concerns from the investors that maybe this indication is small compared like a lung cancer, breast cancer. If you look at the history, the first-generation imatinib, Gleevec, actually just in the CML alone at the peak sales before patent expiration is almost $5 billion peak sales annually, right?

I think overall the current the CML market globally, the total annual sales is about $7 billion. Asciminib last year already reached more than $1 billion sales.

I think there's a estimate the potential just CML global market, the peak sales can reach over $14 billion. I think this is also supported by the Merck acquisition of Curis, primarily for the CML drug, CUDC-701.

That's really great news, great stimulation for the market, for the investors' confidence in this indication and novel drugs. To answer your question, I think we are really also happy we entered the option agreement with Takeda about 2 years ago, June 2024.

I think globally, Takeda will be our partner. I think as in the CML and the ALL space globally, Takeda is really one of the leading company, aside from Novartis.

I think Takeda will be our strong, the best commercial partner for olverembatinib moving forward. The third part of your question is about the registrational trial of the two drug, right?

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

I think we currently push forward really full speed, best effort for the GLORIOSA-4, the high-risk MDS registrational trial, and also both POLARIS-2 and the POLARIS-1 for the olverembatinib. I think POLARIS-2 or POLARIS-1, POLARIS-2 is 6 months MMR rate after the last patient for the potential accelerated approval.

The POLARIS-1 is 3 months MRD-negative CR rate. I think once we complete enrollment, those two probably most likely would have opportunity to file the NDA in 2027.

The GLORIOSA-4 actually also have good chance because we enroll patient really fast, as in this indication with BCL-2 inhibitor, we are the only registrational trial globally for high-risk MDS because many drug failed, including venetoclax trial was negative. We do see a really strong interest and really good enrollment in that space.

With the current protocol achieved, I think this is in my 20 years drug development record, is really the first time for the registrational trial of the same protocol approved, cleared by multiple regulatory agency in the same indication. As in our CLL, we actually did three different registrational trial because different landscape and the different regulatory requirement.

I think we're very happy to see the GLORIOSA-4 registrational trial enrollment is actually really promising, and with potentially also looking forward to have the NDA filing in 2027.

Perfect. Thank you.

Hi, Dr. Yang and Ascentage team.

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

Just continuing on the theme of the last question. Just was wondering if you could characterize olverembatinib's profile relative to Curis' 701, particularly around the 24 weeks or 6-month MMR rate, with your existing data.

Then just as a follow-up, on I know you have a POLARIS-2 study going, but just curious about potentially expanding into second-line or earlier lines in CML. What's the progress on that one?

Thank you.

Thank you. Really good question.

Obviously we're really happy to see Curis acquisition and also 11 data presented at the ASH last year. I think olverembatinib really have a unique advantage based on the clinical data, right?

We probably the same ATP-binding inhibitor as 11, and the Curis is more like asciminib as allosteric inhibitor. Do remember both drug are in Phase I or Phase I/II slash, and but they have much less patient number compared to olverembatinib.

At least based on current data, they're less than 100. Also the dose in terms of for the RP2D or registrational trial has not established for both drug.

At least based on the current published data, it's not clear they work on any the gatekeeper mutation, T315I, or those with compound mutations is not reported or based on the asciminib data required 5 times dose for those with T315I mutation. Clearly there's no long-term safety data or efficacy data, and there's no also a report on any efficacy in the Ph-positive ALL.

Specifically if you look at the you mentioned like MMR rate, I think one is much less patient population patient number, but more importantly, if you look at the line of prior treatment. We published the data on JAMA Oncology year ago and also have the presentation at ASCO and ASH that the patient population we treated in US primarily with PIs from the MD Anderson and others were heavily pretreated.

They are represented the CML patient of fourth or fifth line, and one-third of them has T315I mutation. I think all the BCR-ABL inhibitor, either kinase inhibitor or allosteric inhibitor, the response is really depend on the patient baseline characteristics and how many prior lines treatment and mutation profile.

I think the of course, this is not head-to-head comparison, but just with the current data, I think we really demonstrated very broad, very potent activities and also long-term safety profile and the efficacy as well. I think the another thing I think for both drugs, especially under the Project Optimus, FDA would require Curis compound and others have to do the RCT, right?

They have to do the RCT trial to get approval. In that case, they also must have a control arm.

It's hard to see what would be the control arm, but this are definitely required based on the Project Optimus, the optimal dose in terms of safety, efficacy, and the RCT design and the control arm. I think overall, we are really confident, especially with our partner, Takeda, we're going to position well for the late-line CML for those with mutation and also very active excellent data in the Ph-positive ALL.

We already published the ASH data for the second-line the CML patients. I think actually in China, the approval label is what we call the near second-line approval because it says two TKI resistant and/or intolerant.

I think we're really confident we will benefit patient for those earlier-line as well. Of course, we'll conduct the more studies, especially after we complete the registrational trial for olverembatinib.

Got it. If I may, squeeze in one more.

Lisa has a really strong start following 5 months of launch. We know that BeiGene has that BCL-2 inhibitor just approved recently as well.

Just curious how that would play into dynamics for Lisa's uptake in 2026. Thank you so much.

I think first in China, we were the first domestic BCL-2 inhibitor commercialized last year. We were at least 6 months ahead of BeiGene sonrotoclax approval in China.

That's number one. Number two, I think based on the current data, safety, and also another thing is the sonrotoclax dose ramp-up is similar to the venetoclax weekly dose ramp-up.

The starting dose for sonrotoclax is actually 1 milligram. The approved dose is 320 milligram.

From 1 milligram to 320 milligram, and with five different dose strengths and take nine steps, okay, to do the dose ramp-up. I think that's really not convenient for patients with CLL and SLL.

Also if you look at the overall safety profile, the SAE, even some of the deaths in that registrational trial and the infection rate and so on, lisaftoclax is probably the best among the currently three market BCL-2 inhibitor. Actually based on the published drug label, sonrotoclax actually have even worse DDI risk among the three drugs.

I think we are confident that we'll continue do well and expand commercial sales, coverage, and also especially the registrational trial globally for the MDS. Also our GLORIOSA-2 and GLORIOSA-3 also approved by CDE and other countries.

The GLORIOSA-2 will offer the patients with CLL the first-line treatment in combination with acalabrutinib in a fixed duration, the 18 months fixed duration with the CIT as a control arm. I think that actually is doing well in terms of enrollment.

The GLORIOSA-3 is the AML. We are also the only AML registrational trial approved by the CDE a year, more than a year ago, and currently actively enroll.

This is the same validated indication, validated protocol. We expect we will do well for both GLORIOSA-2 and GLORIOSA-3 in China and a few other countries.

Of course, they both are not for the US and Europe because the control arm or because the trial design. I think to answer your question, I think we will do well, not just because we are 6 months ahead of approval for sonrotoclax, but based on the really excellent drug properties and the clinical data and as well as the multiple indications, we are more in advanced position than sonrotoclax in China or globally.

Great. Thanks for taking our question.

Two questions from us. In terms of the China opportunity and your ongoing launch there, is there a target number of hospitals that you aim to have under formulary for both products that are there?

Just trying to get some visibility into the long-term opportunity and peak sales potential for both drugs. The second question, coming back to your BTK degrader, certainly focus on the oncology side of things, but do you have any plans or intention to go into non-oncology opportunities, such as I&I or CNS diseases?

Thank you.

For your first question, I think the hematology-oncology commercialization in China is really unique, because in China, those disease and treatment are highly concentrated to some of the top hospitals or cancer centers. Our aim is to cover at least 80% of the sales potential.

That represent probably around 2,000 hospitals, okay? We already covered about 1,500 hospitals, okay?

The commercial team for the hematology-oncology is really different than like a solid tumor, lung cancer, breast cancer, as those indications probably need easily probably 2 to 3,000 sales force to cover the 80% potential sales. That's the benefit to develop the hematology-oncology product in terms of commercialization in China.

I think we currently have 300 staff in the commercial team. We'll continue to expand that to about probably 400 to 500.

Then they with much deeper coverage probably close to about 2,000 hospitals. The second question, I think it's a very interesting.

As I mentioned, one of the reason we feel that BTK degrader even though we are not the first one, but it's not really too late. The first is at least is validated target.

Also the BTK degrader can take care many of the inhibitors, it doesn't matter it's covalent, noncovalent, mutation or not. That's one.

Second is, as your question pointed out, the BTK degrader, like some of the other BTK inhibitors, that actually have more probably potential in non-oncology, some of the autoimmune diseases. Also with just probably a little bit CNS penetration, which we have based on the preclinical data, those may actually to treat some of the CNS indications as well.

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

Hey, great. Thanks, Dr.

Yang, for the question. Just wanted to piggyback on some earlier comments on the BTK degrader, particularly the ability to combine with Lisa in earlier-line settings.

I guess the 30,000-foot view question here is do you think the CLL market is heading in the direction of an all-oral, time-limited therapy a la CLL 117 trial that we saw at ASH? How do you think that setup plays to Ascentage's favors here with BTK degrader and lisaftoclax?

Thanks very much.

Excellent question. I think obviously the BTK inhibitor is well-established for the CLL/SLL globally.

The current inhibitor already generated annual sales more than $14 billion. That's a huge benefit.

At the same time, as you pointed out, the CLL, especially some of the young patient with the CLL, they don't like to take either BTK or BCL-2 inhibitor for the lifetime, right? The fixed duration, especially the combination of the BTK currently mostly inhibitor with BCL-2 inhibitor, really offer the patient another option.

They don't have to take the drug a lifetime, right? The current data pointed out actually at least the combination BTK inhibitor primarily with the inhibitor offer a good benefit in terms of really durable PFS over 5 years, right?

The BCL-2, our drug, lisaftoclax, having very unique benefit in terms of other inhibitors, is that we don't have a DDI issue. We don't have DDI issue with BTK inhibitor, much less DDI risk with other potential antifungal drugs.

That's very important. Then on top of that, with the degrader, it's not too late because they take care any of the inhibitors' issues, mutation or not.

I think our plan, and hopefully we can demonstrate that with the clinical data, is that the BTK degrader combined with lisaftoclax, first is to offer the fixed duration and be able to have long-term benefit in terms of PFS. Then in certain cases, because you offer the best treatment regimen early on, then you may actually offer the clinical cure for some of the CLL patients.

That's in the CLL/SLL space. Number two is from the BTK degrader, I think another potential, especially in combination with the BCL-2 inhibitor, maybe offer some the hard-to-treat disease like DLBCL or in the case the BTK single agent failed the patients, right?

One of our strategy globally is our GLORIOSA trial, it's add-on strategy. Because the single agent alone of BTK inhibitor or degrader probably at least half of them cannot achieve the optimal response in terms of CR.

In that case, you combine with the BCL-2 inhibitor, what then offer the patient better response, deeper response, and potentially in terms of fixed duration to stop the treatment with a long PFS. I think Ascentage is really in a unique position to having both the BTK degrader and the BCL-2 inhibitor for those multiple indications.

Appreciate it.

Thank you.

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

First, our current partner agreement is for the option agreement, right? Because they have competitive product of ponatinib, that's based on the some of the antitrust rules.

There are cases before that in the antitrust issue that they may have to return the drug if there's that competition, the antitrust issue. The current agreement, but still is exclusive global partnership.

Basically, both Takeda and Ascentage are bound to have that partnership to work together. That's number one.

Number two, of course, they have to get either clear antitrust or to wait the patent expiration of ponatinib, which I believe is later this year or early next year. I think with that patent expiration, then there's no issue in terms of antitrust issue.

Thirdly, I think for your question, of course, first of all, we already a partner, we are strongly bind, exclusive. The same time, in terms of when to exercise the option, which I honestly cannot speak for my partner.

With the Merck acquisition of Curis for over $6 billion, I think that there's no reason that we do not work together and maybe work together early in terms of exercise the option as your question. I do think is a benefit to both parties that we push forward full speed on the olverembatinib commercialization for the global market.

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

I think we are really open and flexible. We as mentioned at the JPMorgan conference, we are open, flexible, be ready to enter any partnership that will benefit bring the synergy with our product and also the complementary resources to commercialization on the large scale and more global market.

Of course, the same time, we are within the timeframe of be ready commercialization in 2 years. Many the expert in the commercialization is that you need to be minimal ready 2 years ahead of your anticipate the commercialization.

I think we are in the position and actively looking for the Chief Commercial Officer. That's more I would say our dual strategy that combines business development partnership and also to build at least in US our commercialization capabilities.

They're not exclusive, they're really work hand-in-hand in parallel. I think either case will benefit strongly our lisaftoclax commercialization at least in US and also through the potential partners either US or global.

I think we are in a really good position in terms of clinical development, be ready for commercialization, and also looking for the partners that can bring the best value to this product and also patients globally.

Got it. Thank you very much.

Thank you.

thanks for taking the question. I had a question about the allosteric inhibitors, and that was answered earlier in the call.

What's the question? Oh,

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

okay. Now I think the current data, first asciminib as allosteric is doing well, right?

Last year, sales more than $1 billion. In certain countries like US also receive the accelerated approval, for the first-line CML.

Also, but the Curis compound 11 do not have data, at least clinical data, to show the activity in terms of T315I mutation, the gatekeeper mutation, and those with T315I mutation plus other mutations, the compound mutations. I think ponatinib, of course, there's patent and the safety issues.

Currently, our strong competitor to be honest, is considers asciminib. They are not active in about 40% of those late-line CML, which require 5 times dose or 5 times cost.

All the drugs based on current data does not show activity or strong activity as olverembatinib in Ph-positive ALL. I think those two based on the current clinical data which olverembatinib has advantage over those asciminib.

And 11 Curis first they are still early, require RCT trial and approval by the FDA. More importantly, I think the late-line we are definitely the best and the most potent one and broad activity against all mutations.

The early-line, I think we are doing the second-line trial. We do have data, early data, to support that.

I think they focus, if you look at the current market share, two of the second-line actually is taking the most market shares. Among the $7 billion annual sales, two of the second-line has been consistently taking each about $2 billion annual sales, okay?

Moving forward, I think the currently there's, including asciminib, there are five drugs with first-line label. For Curis or any other compound try to moving into the first-line is going to be uphill battle and they also take a long time and really costly.

I think our focus really moving forward, and also based on the data, is probably a olverembatinib could be the first choice of the TKI for the second-line patients. In that regard that we don't worry about the competition of the first-line, or actually more first-line treatment, the patient will funnel through to olverembatinib in terms of the best the second-line treatment.

Thanks for taking the question.

Thank you.

First, thank you all for attending and also really excellent insightful questions. This is a really timing in terms of the our annual report for 2025, representing the first year we are have a dual engine for commercialization, build a full-scale, functional sales force, and also the first time as a dual-listed, dual-primary listed company on NASDAQ.

Moving forward, we also see really strong confidence and broad potential in CML, ALL, and also really they probably cornerstone product for hematology oncology with our selective BCL-2 inhibitor. We are probably in a really best position in global novel product development that not just being the the first approval commercialized in China in those products and indications, but globally, we are the potentially best-in-class with clinical data in terms of safety, efficacy, and also in the registrational trial.

I think that's really unique position. At the same time, of course, there's a huge potential in terms of commercialization readiness in US and also looking forward to our the partners for the global market in expansion.

We are really excited with our strong achievement, the milestones, transformation year for 2025. Looking forward, we are more excited to see all the registrational trials advance well, looking forward to have be ready to have the commercialized in US, being the global leader in those therapeutic areas with best-in-class potential drugs for multiple hematology malignancies, and looking forward to working with you all and all the investigators and investors around the world to bring the best drug to benefit patients globally.

Thank you all. Have a good day.

Thank you.