Ascentage Pharma Group International ($6855)

Good day, everyone, and welcome to Ascentage Pharma's 2025 Annual Results Earnings Call. [Operator Instructions] As a reminder, today's call is being recorded. Thank you for joining us. I will now turn the call over to [ Julie Chen ], Senior Director of Investor Relations for the safe harbor statement. Julie, please go ahead.

Thank you, operator. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions. These statements involve risks and uncertainties and actual results may differ materially. For a full discussion of these risks, please refer to our filings and disclosures. On today's call, I am joined by Dr. Dajun Yang, Chairman and CEO, who will provide an overview of recent developments and 2025 annual performance. As well as Dr. Veet Misra, CFO, who will go through the financial highlights. The presentation will then be followed by a Q&A session. During the Q&A session, the team will be joined by Dr. Yifan Zhai, Chief Medical Officer; Dr. Shaomeng Wang, Cofounder, Chief Scientific Adviser, Dr. Zhichao Si, Head of Commercial, I will now turn the call over to Dr. Yang.

Thank you. Good morning. I'm Dajun Yang, Chairman and CEO of the company. Today, I'm very happy to present our 2025 full year financial results and a corporate update. I will have the following agenda, business update, R&D highlights, financial results and the Q&A session. First, on the business update, 2025 was a breakout year for Ascentage. First, we have achieved excellent total revenue over 90% of growth and totaled $82.1 million. Our year-end cash balance is about $353.2 million, cash runway through 2027. I think 2025, we are the first dual listed biopharmaceutic company on NASDAQ following our Hong Kong Stock Exchange listing 2019. We successfully raised approximately [ $326 billion ] through IPO and a follow-on offering. It's the first time we have a dual commercial product, based on that, we established a fully functional large scale and fast-growing commercial team, currently close to 300 staff. We are on the path to be a premium global commercial hematology oncology company. We also achieved many major R&D achieved milestones, these are the following examples. First, the [ SOFR ] approval as a global first single-agent Bcl-2 inhibitor after BDK treatment in CLL and SLL. GLORA-4 Phase III registrational trial received clearance globally, including FDA, EMA and CDE. This is a truly unique opportunity as we are the global Phase III reduction trial in high-risk MDS, the only one in the Phase III registry stage. For Lars, for the PH part AL, the Phase III registration trial also received clearance globally, including FDA, EMA and CDE. [ HARDI ] data also reported at ASH demonstrated strong 64% and MRD-negative CR rate in the first-line PSL. Or imbatentiv granted a breakthrough destination for the first-line treatment of PG AL by CDE. We are also very proud to have FDA and CDE IND clearance for our normal BDK degrader APG-3288. Both the server class and over martini entered 2025 Cisco guidance, multiple oral presentations at ASCO and ASH 2025. We continue to lead in the global innovation for many of our products including multiple presentations at ASH, AACR, ASCO, EHA and other conferences. And also, we published many peer-reviewed top journals. I think here is our summary of world-class innovative, highly derisked and super late-stage pipeline. We have the list of 7 novel compounds. The first 2, Olverembatinib, as a novel third-generation vital inhibitor and restore class as the normal Vista inhibitor. Both have been marketed in China and also entered for global registration trial cleared by FDA EMA, and total, we actually have 9 registration trial for multiple indications. We also have several novel potentially first-in-class compound targeting such as the FAK ALK, ROS1, Triple Conix and MD2II, the DuraFit XL and the PRC2 third generation like the EED inhibitor. And more importantly, we have newly cleared Phase 1 novel BDK degrader, APG-3288. All of these are running the trials in U.S. and China and in multiple countries, mainly focus on hematology/oncology, but also have a potential and also in the clinical state testing indications such as anemia. So we have built a very large commercial scale in China with a dual product approved especially for our [ BGI/inhibitor ] self class was ahead of our schedule last year. And with the 2 commercial products, we have built over 270 by the year-end commercial team covered 1,500 hospitals and more than 800 GDP pharmacies. I think our dual engine strategy working well. As you can see, our last year commercial revenue, I think that's a transition for Ascentage from being you rely on the investment investors and also BD income to the last year, 100% sales of the commercial stage product. I think that, that's a really important transition for the company to be able to self-sustain with our own revenue to support our own R&D program. If you look at just our Mateon, we have a strong sale following 4 NRDL listing covering CML with without mutation. So if you look at the total sales, reaching $62.2 million, that represents 81% year-over-year growth. and they will continue to cover more hospitals, DTV pharmacy and also a broader reach to the Tier 1 hospitals. And with the full NRDL coverage and also translating into very long DOT that will support sustained growth as the patient continue to use our drug over a long time. If you look at the reserve class, first, this July approval was ahead of schedule. And we built a very fast and full functional commercial team dedicated to the supercars. So the streamline go-to-market strategy using the national commercial infrastructure really helped us to rapidly expand the sales force and hospital coverage. So just the first 5 months, we have reached more than USD 10 million sales. This is, I think, is among to, at least in the hematology oncology product sales in the first couple of months in China. And then let's go to the R&D highlights. First, let's look at our discover class is actively advancing its global Phase III registrational trials. First, our approval as a single agent for CLL, CSL, after BTK inhibitor is already represented the first label for the Bcl-2 select inhibitor. As you know, venetoclax was approved 2016. And continually, the only single agent was limited to the [indiscernible] , CLL and SLL, the other CLL is all combination with CD20 antibodies. Our GLORA-2 and GLORA-3 also received FDA EMA and the CD clearance. And more importantly, I think that the GLORA-3 is the first-line high-risk MDS in combination with AZA or without azacitidine control arm, both received -- I mean, received the FDA, EMA and the CD clearance will continue pushing forward all these important global Phase III rejection trial. I want to share a few important clinical data with you. First, with the single agent approval, based on the CC201 regutration study, those patients actually have a much poor baseline characteristics. First, the CV actually give us a very high bar about 4, 5 years ago, required all these CRS patients have to fill both BTK and CD20 antibody-based therapy. Many of them have a high-risk complex [indiscernible] and also many have multiple mutations. So we achieved a very good efficacy as a single agent and demonstrate a favorable safety profile. If you look at another key data in the AML and MDS. Actually, this is primarily U.S. and Australia data with the leading PI from the U.S. And this actually has presented both at the ASCO and ASH. If you look at our ORR as a combination with ASA, in the naive, the Unidas -- AML patients, we achieved ORR 83%. And more importantly, in some cases, about 22 patients who have failed in the class. We also achieved 32% or in the MDS, we have in the newly diagnosed 80%. And in the second line, our MDS, we have 50% or I think based on those excellent data and many other clinical data, FDA gives us clearance to conduct global Phase III rejection trial as the first line for the high-risk MDS. And this has been cleared by FDA, EMA and CD Among close to 20 countries, regulatory agencies. So we are actively enrolled patients in U.S., Europe, China and throughout the world. So if success has carry out, the [ sofa ] can become the first vest inhibitor for the treatment of first-line high-risk MDS. This is really a global mathematical need as there is no target serve approved in the last 20 years. And current therapy have much poor efficacy and 5-year survival rate for high-risk patients is only about 16% to 24%. We are also very proud these global efforts leading by as [indiscernible] Monero from [indiscernible] and Dr. [indiscernible], from picking University People's Hospital and many, many excellent expert PIs for MDS around the world. Based on the public information, we want to highlight a few key differences of our drug versus another class or surrender class. If we look at -- based on the same similar registration trial study, again, this is not a head-to-head comparison, but a really similar patient population, including those in China. So if you look at the SAE instance is much higher for -- or surrender class and the infection rate also significantly higher. So that's consistent with the clinical observation that these costs have a better safety profile, better tolerance. And more importantly, we have a better drug combinability. CLL patients often or elderly and immunocompromised with frequent infections. Common used antifungal drugs are strong 3A4 inhibitors. And but does not affect our reserve class PK. So if you look at the PK variability in combination with some strong 3A4 inhibitors. I think that the impact for the superclass is minimal for other two drugs either need about 8x or 11x need to be an adjusted dose if they are combining those. That will strongly affect clinical combination studies. And also look at the PDP or BCRP substrates or inhibitors, the surplus is probably the one of a minimal risk in those combination studies. No need to adjust those with like many BTK inhibitors. I think that those are very unique advantage for the server class 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 we see acenecommercial coverage and the revenue growth last year. Globally, we are conducting POLARIS-2 for the CML and this single-agent study RCT with the Boseto control arm also received FDA, EMA, CDE and the PMDA clearance. So we are actively pursuing advancing the global enrollment. POLARIS-1 is very important. This is the first time we got a clearance last year. For the first line Post -- and this is also clear by FDA, EMA and the city in China with a breakthrough destination. Part of one of this trial, the same trial design data was presented at ASH. And you can see the data from the next couple of slides. First, in the Part A of the Phase III registration trial in combination with low-intensity chemo as the first line, we have achieved 64% margin [indiscernible]. This is almost double the same patient population for the ponatinib, which only have 34.4% MRD negative CR rate but this actually is among all the visa inhibitors, the best one. So we actually almost double the currently the best desal inhibitor for the same patient population and also demonstrate very well safety profile. Another data is looking at a potential second line treatment for the CML CP patients. This also, again, presented at the ASH last year. We can achieve more than 50% -- I mean, 70% state, 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 space and also some serious cytogenetic anomalies and comprise terotypes. And those patients did very well and also into the sustained remission with improved survival and a much reduced not relapse mortalities. Another potential treatment is really for the combination with our Olverembatinib. And in this case, it's actually in the pediatric patient population that is a first-line regimen in the PH positive demonstrated ready acid efficacy and the safety profile. I think that this would be really important for some of the patients to receive the team of 3 and the 2 orally active agent with a long-term benefit. Olverembatinib as multiple kinase inhibitors also demonstrate clinical benefit for some rare hematological malignancies such as this is very hard to treat millimole plasm with the FGFR rearrangement. And this actually takes a while to recruit those patients, but most of them achieve the accident response, clinically. And we continue to push our pipeline. In the interest of time, we only show you one example as our novel BTK degrader APG-3288. This actually we reserve almost the same time clearance by FDA and CDE. And based on the preclinical data, I think we also did a comparison with Ben or Nurix BDK deviator demonstrate good selectivity and potency. And we're pushing forward this compound in U.S. and China for multiple indications. I think in summary, these costs as a very safe and potent Bcl-2 inhibitor, -- some refer Bcl-2 inhibitor as a small molecule of PD-1 that really means it has multiple indications and also opportunity for multiple combinations. But I think more importantly, we probably globally the only company has not just the Bcl-2 inhibitor, but also on bartender representing the best third generated visa ARPO inhibitor and MD2 PPI inhibitor and also the novel new PDK protein be greater. As you can see, each one of these is a single agent or in combination, have potential to treat a mutiple resell malignancies among many hematological malignancies. Lastly, I think I will turn the financial results to our CFO, Veet. We -- we also go to the Slide #28.

Thank you so much. Yes. So 2025 was a successful year for us as we established our commercial strength with now 2 approved novel oncology products. In 2025, our total revenue was USD 82.1 million, excluding payments from Takeda as a comparison to last year, which represents a year-over-year increase of 90% on a constant exchange rate basis. This high revenue growth rate was driven by our aforementioned dual-engine commercialization strategy as articulated by Dr. Yang and centered on Olverembatinib and Lisaftoclax. Turning to Olverembatinib and Lisaftoclax individually, Olverembatinib sales of USD 62.2 million represents year-over-year growth of 81%. Sales of this product reflected first full year -- first full year of NRDL inclusion, hospital and DTP market penetration, which drove increased volume uptake. Turning to Lisaftoclax, which was approved in July 2025. First 5-month sales of $10.1 million was attributed to our established commercial infrastructure that was built to scale ahead of approval and is anticipated to drive strong market penetration going forward. At the same time, we continue to adhere to a disciplined approach to efficiently manage and prioritize our operating expenses to support accelerated commercial activity, as well as our ongoing clinical studies, including global registrational trials. As you can see, our year-over-year increase in R&D expense from USD 130 million to USD 163 million year-over-year, which is tied to advancing ongoing global pivotal studies represents a 20.1% growth rate to support trials ongoing to -- that are expanding and moving forward. In addition, the increase in S&D expenses, sales and distribution in 2025 from USD 27 million to USD 51 million was primarily driven for sales force expansion ahead of commercial launch of Lisaftoclax, which is an efficient use of capital. So as you can see, the increase in these 2 major line expense items compared to our revenue growth demonstrates our disciplined approach. Finally, in terms of our cash balance, our 2025 year-end cash balance of USD 353.2 million compared to USD 172.8 million reported year-end 2024 is a result of product sales and two completed successful financings in 2025. Our January 2025 NASDAQ IPO as well as our follow-on offering in July 2025 on the heels of Lisaftoclax approval, raising combined proceeds of $322.6 million. So as a result, this allows us to maintain our estimate of cash runway through 2027, as we've stated before, which importantly funds us through multiple key registrational studies that are being conducted globally and execution of our overall commercialization strategy. Thank you. I'll now turn it back to you, Dr. Yang.

Thank you, Veer. I also want to present our clinical catalysts and milestones for 2026. On the clinical development side, our major focus will be an advanced enrollment for the GLORA and GLORA-4 reiterated trial and also advanced enrollment for Olverembatinib in terms of POLARIS-2 trial and also POLARIS-1 trial. I think as we mentioned earlier with our team, I think the keyword for 2026 is really the enrollment and home. I think we'll do our best to achieve a complete enrollment and then be able to file in 2027. We'll continue to push the greater APG-3288 global Phase I study in terms of safety, tolerability, PK and potential efficacy data and then also advance our ED inhibitor APG-5918 in both oncology and anemia. Of course, we'll continue to push other active compounds in clinical study in U.S. and in China as well. But I think the major in terms of milestone for the clinical development, those highlights here. On the commercial front, we will continue to drive the sales growth for our Olverembatinib and also the Lisaftoclax to the Tier 1 hospitals and more pharmacies. And for the subclass, we will do our best for the benefit of patients, especially CRS, together to the NRDL coverage in China in 2026. I think that the key driver for advantage to be a global player in hematology/oncology is really driven by the 2 novel and potentially best-in-class compound Olverembatinib and Lisaftoclax. We also have a dedicated hematology oncology sales force not just based on the really rapid scale in China, but more importantly, our global strategy positioning and branding I think with our world-class clinical execution and a proven track record of translating the clinical development into the novel commercial product and advance our best-in-class potential therapeutics in global regulation studies. I think with the dedication and the effort from all our team and also our collaborators and the PIs are around the world, we're really moving our pipeline to addressing the global medical need making advantage to become the global leader in these therapeutic areas. Lastly, I think with the patient-centric innovation and global breakthrough therapies and with currently 7, we'll call the 7 magnificent, 7 active compound, small molecule drugs in active clinical trials, addressing multiple hematology malignancies from the CML ALL to CLL, AML, MDS, modern myeloma and potentially some of the lymphomas and anemias. Hopefully, with the oil support, we can make another successful year for advantage. Thank you all for your attention. And now we will be happy to answer any questions you may have. Thank you.

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

Maybe just first, Dajun, you talked about how this year is really about on [ Roman and Roman ]. Can you give us a bit more color on where you are in terms of enrollment for your registrational studies, especially the GLORA-4 study in MDS with Lisaftoclax and also the POLARIS-1 study in ALL. And related to those indication, how should we think about the next data milestone at the upcoming medical conferences later this year?

Thank you, Brian, very excellent question. I think let me maybe address this to 2 parts. First, for the GLORA-4, high-risk MDS. We are very happy to see this Phase III, which trial protocol received clearance by not just the FDA, EMA, CD and also moms [ 20 ] countries agency. And this is the first-line treatment for the naive or treatment-naive unit diagnosed high-risk MDS. And more importantly, this is not really the only Phase III reduction trial in the high-risk MDS globally. And we are very happy to receive the support from the PIs around the world. and they're very tucatic for this clinical trial to help patients globally with MDS. And with the POLARIS-1, this is the first line PSL. As you know, we also presented a part 1 of the same protocol data at ASH the 3 months margin active rate CR is 64%, almost double the [ ponatinib ] and the same patient population about only [ 34% ]. So I think that the -- those 2 registration trials both for the first-line treatment, which will actually much easier enroll than some of the late line protocols. And of course, also have a huge potential market return. And with those 2 first-line treatment, and you can see MBS, we are the only 1 from the runner in the Phase III edition trial globally. There's almost no competition there. The POLARIS-1 is the first line for the PH-sealso with excellent data, potentially the best-in-class for the PH patient population. So I think the enrollment are doing well. And even though both only initiated late last year. But we see so far the very excellent enrollment and very strong support from the health care providers around the world, and the POLARIS-1 only requires 3 months MRD-negative CR for -- as a primary endpoint. And also, we have a strong support from FDA and all the regulatory agencies to support the protocol of the GLORA-4. I think that the -- overall, we will do our best to achieve complete enrollment. And with the current -- the time line and the primary endpoint, we anticipate to do the best we can and then to be able to release the top line data or complete enrollment and then be able to file NDA for -- in 2027.

Got it. And maybe just one more. Just how do you think about the commercial growth opportunities for both Olverembatinib and Lisaftoclax franchise this year in China. Are there any specific drivers that you see today that your sales team is fully leaning on? And then perhaps we actually have a follow-up after this.

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

Yes. Okay. Thank you for the question. And -- if you look at the actual driver of growth in 2025 in China, I believe there are several key drivers. And first of all, if you look at Olverembatinib and which really benefit from the for the broader reimbursement support affordability after IND inclusion, which Dr. Yang also mentioned and also very strong patient affordability improvement. And second, if we look at our annual report, we continue to expand the hospital and D2C pharmacy access with more than 800 hospitals and D2C pharma, we significantly improved the accessibility by the year-end which also includes more than 355 hospital with formulary access in hospital listing is a very important Italemarket. And third, I believe if you look at the Lisaftoclax, which was approved in China, and since July, and we got sales for 5 months. And the cyber class, I mean, really give us a second growth engine after launch and generating more than RMB 70 million in the first 5 years on the market. And fourth, I think we scale the commercial organization and Dr. Yang and Dr. Veet with both mentioned, we scaled up our commercial organization, admittedly, our team actually owns tripled compared to 2025 -- compared to -- 2025 compared to 2024. And this commercialization team growing more than 270 people and converting more than 1,000 and 500 hospitals net-wise. I believe that's the key driver for the last year's commercial growth. Thank you.

Great. And then maybe just lastly, I just want to touch on your BTK degrader here. Dr. Yang, can you first give us a better sense of how you see differentiation compared to other BTK grade that's out there? And then as you think about your Phase I study, what would be good to see from this initial Phase I?

Brian, very good question. For the first maybe clinical part, I will have our Chief Medical Officer, Dr. Zhai to address. Yifan, can you hear? So if not, maybe let me try to answer your question. So first, we have conducted a very thorough of course, is currently preclinical data to compare our BTK integrator with Ben or Nurix. I think that based on this comparison, we selected our candidate compound moving into the Phase I and based on the preclinical data, at least, we show better selectivity and also more potency. That's number one. Number two, I think that the -- as the BTK is a validated target, the BTK degrader can take many of the BTK inhibitors covalent, non-covalent mutation or not basically have a broad efficacy in the oncology space. I think the most unique for Ascentage. Once we go through the Phase I, typical safety, tolerability, PK and some signal of efficacy with the potential RP2D, we probably move very quickly into the potential single-agent indications to -- for the fast-to-market approach. The second part, I think, are unique to Ascentage that we have a very excellent Bcl-2 inhibitor. So the combination of BD inhibitor or degrader and the Vicat inhibitor could already offer some of the hard-to-treat patients benefit. And in the case of the CSL with a fixed duration is really potential even in some case conical cure. That means there's no progression after 5 years treatment, I mean, stop treatment I think that, that will also offer additional benefit, especially for the young patients, which is the CRS. And in combination with the Bcl-2, maybe also can treat some harder trade like DLBCL. I think thirdly, I think also at this part of our moving forward strategy, potential, the maximal return is that there are also many non-oncology indications for the BTK degrader like autoimmune diseases. I think with all the -- those 3 reasons, we are really looking forward to full speed to push this novel BDK degrader into the kinetic development and many other potential combinations and indications.

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

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

The 2025 was the first year for the NRDL coverage. And especially for the with or without mutation. And so the patient population compare our first approval indication with [ T315 ] mutation only we -- the patient population more than triple. That's number one. The NRDL coverage for this chronic patient is really significant as they can average nationwide can reduce at least 70% the payment -- and in certain better economy -- the countries, I mean, to province, the reduction payment can be reduced by 90%. So that's really significant as these patients are taking the drug a long time, right, very good long DOT. So the NRDL in China for the CML patient we see really benefit important benefit. The patient population in China as other late-line treatment, like you mentioned, a cinema or phenomena, 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. But overall, the physicians and the patients are really well-educated position once getting into the full NRDL coverage. For both asciminib and ponatinib they were not under NRDL coverage, okay? So that's also limit the use of those two drugs only have got approved a year ago. So they are not really much sales affordability for those other and covered the cinema or ponatinib in China. Then moving forward for 2026, we see the benefit of NRDL will continue as the price is good for 2 years. And if we just looking a little bit next year, ahead of NRDL renewal, we're also very confident as the new policy from the is to maximize the support for the novel agent and also those unmet medical needs I think [ is 1 ] of the examples falling into the category with a strong support by the NRDL. And also, we currently, another important indication, also really high-prevalence disease is [ Porto ] in the real world, we do have many PS post patients benefit by the rate. But at the same time, because they are not officially into the NRDL coverage. So currently, in dose patient population, we still want to finish our rerating trial, be able to guide into the deal. So moving forward, I think that there's a continued expansion and the growth of the revenue for a martini in China, both the CML and the [ PHP ].

And maybe just a follow-up. Clearly, there's a lot of focus on the CML treatment landscape, especially yesterday, Merck announced acquisition of turns for $6.7 billion. How do you think Olverembatinib would fit into the emerging treatment landscape in the U.S. for CML. And then second question, which of your global pivotal trials across both ovaremvatinib and Lisaftoclax? Can we expect to see data in 2027?

Really asking question. And actually, we are all very excited to see the acquisition of the terms by Merck with, obviously, a very good price, $6.7 billion in all cash. I think the positive side is really that means the CMO market globally is actually quite a big right? So to be honest, a couple of years ago, when we were developing over matinib, there are some concerns from the investors that maybe this indication is small compared like a long tenor breast cancer. But if you look at the history, the first generation, the email actually, just in the CML alone, the peak sale before partner expiration is almost [ 5 billion peso ] annually, right? So I think overall, the current CML market globally, the picket is about, I think, the total annual sales is about $7 billion. And as sentiment last year already reached more than [ 1 million ] loss. So I think there's an estimate the potential just a CML global market, the [ pixel ] can reach over $14 billion. So I think this is also supported by the Merck acquisition of terms primarily for the CML drug, turn CML. So that's a very great news, great stimulation for the market, for the investors confidence in this indication on novel drugs. To answer your question, I think we are very also happy we entered the option agreement with Takeda about 2 years ago, June 2024 I think globally, Takeda will be our partner. I think as you know, in the CML and the AR space globally, Takeda is really 1 of the leading company aside from the Novartis. I think that Takeda will be our strong, the best commercial partner for Olverembatinib moving forward. The third part of your question is about the registration trial of the 2 drugs, right?

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

Yes. I think we currently pushing forward really full speed for the best effort for the GLORA-4 the high-risk MDS regain trial and also both POLARIS-2 and POLARIS-1 for the over martini. I think the POLARIS-2 or POLARIS-1, POLARIS-2 is a 6-month MMR rate after the last patient for the potential accelerated approval. And the POLARIS-1 is 3 months MRD-negative CR rate. So I think once we complete enrollment, those 2 probably most likely would have an opportunity to file the NDA in 2027. The GLORA actually also have a good chance because we enter, I mean we enroll patients very fast. As in this indication with the Bcl-2 inhibitor, we are the only registration trial globally for high-risk because many drugs fell, including Werner trial was native. So we do see very strong interest and very good enrollment in that space. And with the current protocol achieved I think that this is -- in my 20 years of drug development record is really the first time for the registration trial of the same protocol approved, clear by multiple regulatory agency in the same indication. As you know, in our CRO, we actually did 3 different registration trial because of different landscape and the different regulatory requirements. So I think we're very happy to see the GLORA-4 registrating trial enrollment is actually really promising and we potentially also looking forward to have the NDA filing in 2027.

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

Congrats on the progress. This is Supawat on for Greg. Just continuing on the theme of the last question. Just I was wondering if you could characterize Olverembatinib's profile relative to [ 10701 ], particularly around the 24 weeks or 6 months, rate with your existing data? And then just as a follow-up, so on -- I know you have a POLARIS-2 study going, but just curious about potentially expanding into second line earlier lines in CML. What's the progress on that one?

Thank you. Very good question. Obviously, we are very happy to see turns acquisition and also 11 data presented at the ASH last year. But I think Olverembatinib have a unique advantage based on the clinical data, right? So we probably the same ATP binding inhibitor as 11 and the turn is more like a cinema as an allosteric inhibitor. But do remember, both the drugs are in [ Phase I or Phase II ]. But they have much less patient number compared to onrateAnd at least based on the current data, they are less than 100. And also, the dose in terms of the [ RB3D or regulation ] trial has now established both drugs. And this is based on the current paper data -- it's not clear they're working on any gatekeeper mutation, [ TC1 ] or those with the compound mutations is not reported or based on the sentiment data require 5 dose for those with TC onetime mutation. So clearly, there's no long-term safety data or efficacy data. And there's no also report on any efficacy in the PEGs. And specifically, if you look at the -- you mentioned like MMR rate I think 1 is much less patient number. But more importantly, if you look at the line of prior treatment, we published the data on Jama oncology a year ago and also have the presentation at ASCO and ASH that the patient population we treated in U.S. primarily with the PIs from the MDS and others were heavily pretreated. They are representing the CML patient for a fifth line and 1/3 of them has T3 onetime mutation. So I think you know all the desirable inhibitor either kinase inhibitor are sterinhibitor, the response is really dependent on the patient based on our characteristics. How many prolines treatment and mutation profile. So I think that the -- of course, this is not to have comparison. But just with the current data, I think we really demonstrate very broad reporting activities and also long-term safety profile and the efficacy as well. So I think that the -- another thing I think for both drugs, actually under the product uptimes, FDA would require turns compound when others have to do the RCT, right? They have to do the RCD trial to get approval. And in that case, they also must have a control arm. So it's hard to see what will be the control on, but these are definitely required based on the project optimist, the optimal dose in terms of safety efficacy and the RCT design and the control arm. So -- but I think overall, we are really confident, especially with our partner, Takeda. We're going to position well for the line CML for those with the mutation and also very active excellent the data in the PH ALL. And we're already conducted published 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 uses 2 TKI resistant and are intolerant. So I think we are really confident we will benefit patients for those early line as well. But of course, we'll conduct the more studies, especially after we complete the redaction trial for Olverembatinib.

Got it. If I may squeeze in 1 more. Lisa has really strong start following 5 months of launch. But we know that V1 has the Bcl-2 inhibitors just approved recently as well. Just curious how that would play into dynamics for Lisa's uptake in 2026.

Yes, I think that the first in China, we were the first domestic Bcl-2 inhibitor commercialized last year. So we were at least 6 months ahead of B1 surrender class approval in China. That's number one. Number two, I think based on the data currently in safety and also another thing is the surrender class, those are not is similar to the node class weekly dose up. And the starting dose for surrender class is actually 1 milligram. And the approval of those is 320 milligram. So from 1 milligram to 320 milligram and with the 5 different dose strengths and taken steps, okay, to do the dose or not. I think that's a very normal for patients with CLL and SLL. And also, if you look at the overall safety profile and the SAE, even some of the deaths in the registration trial and the infection rate and so on the subclass is probably the best among the currently 3 markets VSAT inhibitor. And actually, this on the published the drug label 1 costs actually have even worse DDI risk among the 3 drugs. So I think the -- we are confident that will continue to do well and expand commercial sales coverage and also especially the retitrate trial among the -- globally for the MDS. And also, our GLORA-2 and GLORA-3 are also approved by CD and other countries. The GLORA-2 I will offer the patients with CLL, the first-line treatment in combination with color in a fixed duration. The 18-month peak duration with the CIT as a control. I think that actually is doing well in terms of enrollment. And the GLORA-3 is the AML, and we are the also the first -- the only the AML registration trial approved by the city a year. More than a year ago and currently active enrolled -- and this is the same validated indication, validated protocol. We expect we will do well for both GLORA-2 and GLORA-3 in China and a few other countries. And of course, they both are not yet not for the U.S. or Europe because they control arm or because of the trial design. But I think to answer your question, I think we will do well, not just because we are 6 months ahead of approval for surrender class. But based on the really an drug properties and the clinical data and as well as the multiple indications, we are more in an advanced position the surrender class in China or globally.

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

Two questions from us. In terms of the China opportunity and your ongoing launch there, is there a target number of hospitals that you aim to have under formulary for both products that are there? Just trying to get some visibility into the long-term opportunity and peak sales potential for both drugs? And the second question, coming back to your BTK degrader, certainly focus on the oncology side of things. But do you have any plans or intentions to go into non-oncology opportunities such as I&I or CNS diseases?

Yes. For your first question, I think the hematology oncology commercialization in China is very unique. Because in China, those disease and treatment are highly concentrated to some of the top hospitals or cancer centers. So to cover our aim is to cover at least 80% of the sales potential that represents probably around 2,000 hospitals, okay? And so we already covered about 1,500 hospitals, okay? So the commercial team for the hematology oncology is really different than like a solid tumor lung cancer, breast cancer, as those indications probably you need easily probably 2,000 to 3,000 sales force to cover the 80% potential sales. So that's the benefit to develop the hematology oncology product in terms of commercialization in China. So I think we currently have 300 staff in the commercial team. We'll continue to make that -- to expand that to about probably 400 to 500 and then with a much deeper coverage probably close to about 2,000 hospitals. The second question, I think, is very interesting. As I mentioned, one of the reasons we felt that BTK degrader even though we are not the first one, but it's not really too late. The first is there's a lot of -- I mean, this is validated target and also the BTK greater to take care of many of the inhibitors, but it doesn't matter covenant non-covalent mutation or not. That's one. Second is, as your question pointed out, the BTK degrader like some of the other BTK inhibitors that actually have more probably potential in non-oncology, some of the autoimmune diseases and also with just probably a little bit China penetration, which we have based on the preclinical data, those may actually to treat some of the CNS indications as well. So we do have a strong covenants and see much huge potential for the Bear in oncology and non-oncology and also with our Bcl-2 inhibitor in terms of combination.

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

Just wanted to piggyback on some earlier comments on the BTK degrader. Particularly the ability to combine with Lisa in earlier-line settings. I guess like the 30,000-foot view questioners, like do you think the CLL market is heading in the direction of an all-oral time-limited therapy, a CLL-117 trial that we saw at ASH? And do you think that, that set up -- or how do you think that setup plays to a sense of just favorite here with BTK degrader and Lisaftoclax?

Excellent question. I think, obviously, the BTK inhibitor is well established for the CSL globally. And the current inhibitor already generated annual sales of more than $14 billion. So that's a huge benefit -- but at the same time, as you pointed out, they still especially some of the young patients with the CLL. They don't like to take either or Bcl-2 inhibitor for the lifetime, right? So the fixed duration, especially the combination of the BTK currently mostly inhibitor with the Bcl-2 inhibitor really offer the patient another option. They don't have to take the drug lifetime, right? So the current data pointed out actually this the combination BTK inhibitor primarily with the inhibitor offer a good benefit in terms of really durable PFS over 5 years, right? And the Bcl-2, Lisaftoclax having very unique benefit in terms of other inhibitors is that we don't have a DDI issue. We don't have a DDI issue with a BTK inhibitor and much less DDI risk with other potential antifungal drugs. That's very important. And then on top of that, with the degrader. It's not too late because they take care of any of the inhibitors issues, mutation or not. So -- and I think our plan and hopefully, we can demonstrate that with the clinical data is that the BTK degrader combined with the server cost. First is to offer the fixed duration and be able to have long-term benefit in terms of CFS. And then in certain cases, because you offer the best treatment regimen early on, then you may actually offer the clinical cure for some of the CLL patients. that's in the CLL space. Number 2 is from the BTK divisor, I think another potential especially in combination with the Bcl-2 inhibitor maybe offer some hard-to-treat disease like the [ DLBCL ] or in the case of the BTK single agent failed the patients, right? So 1 of our strategy globally our GLORA trial, this is an add-on strategy. because the single agent alone of BTK inhibitor or degrader, probably. At least half cannot achieve the optimal response in terms of CR. So in that case, you combine with the G2 inhibitor, will then offer the patient better response, deeper response and then potentially in terms of a fixed duration to stop the treatment with the long -- so I think the acetate is really in a unique position to having both the BTK degrader and the VC2 inhibitor for those multiple indications.

We will take our next question. Your next question comes from the line of Christopher Liu from Lucid Capital Markets.

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

First, our current partner agreement is for the auction agreement, right? Because they have a competitive product, ponatinib, that's based on some of the antitrust rules. And there are cases before that the trust issue that they may have to return the drug if there's that competition antitrust issue. So the current agreement, but still is an exclusive global partnership. So basically, both Takeda and Ascentage to have that partnership to work together. That's number one. Number two, of course, they have to get either clear antitrust or to weigh the patent expiration of ponatinib which I believe is later this year or early next year. I think that with that pattern expiration, then there's no issue in terms of antitrust issue. Thirdly, I think for your question, of course, first of all, we're already a partner. We are strongly bond exclusive. But at the same time, in terms of when to access the option which I honestly cannot speak for my partner. But with the Merck acquisition of turns for over $60 billion, I think that there's no reason that the we do not work together and maybe work together early in terms of excess the option as your question. So I do think that is a benefit to both partners that will move forward, pushing forward full speed on the over commercialization for the global market.

And for Lisaftoclax, would you be looking to partner that asset as well? Or are you pretty adamant about going alone with that asset? I think we are really open and flexible. We -- as I mentioned, at the JPMorgan conference. We are open flexible ready to enter any partnership that will benefit -- bring the synergy with our product and also the complementary resources to commercialization on the large scale and the more global market. But of course, at the same time, we are within the time frame of be ready commercialization in 2 years. And many the expert in the commercialization is that you need to be minimal ready 2 years ahead of our anticipated commercialization. So I think we are in a position and actively looking for the Chief Commercial Officer, that's more, I would say, our dual strategy that combines business development partnership and also to build at least in U.S., our commercialization capabilities. They are not exclusive. They are really working hand in parallel. I think in either case, it will benefit strongly our reserve class commercialization, at least in U.S. and also to the potential partners, either U.S. or global. So I think that the -- 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.

We will take our next question. Your next question comes from the line of [ Michael King ] from [ Rodman & Rental ].

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

So what's the question?

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

Okay. No, I think that the current data for asciminib as laser is doing well, right? Last year, it sells more than $1 billion. And in certain countries, like the U.S. also received the condition of approval -- I mean, accelerated approval for the first-line CML. So but the turns compound 11 do not have data, at least clinical data to show the activity in terms of T3 onetime mutation, the gatekeeper mutation and those with [ 3111 ] other mutations, the compound mutations. So I think the -- I mean ponatinib, of course, there's a patent and safety issues. So currently, our strong competitor, to be honest, we consider asciminib. And -- but they are not active in about 40% of late-line milk which require 5 or 5x the cost. And all the drugs based on the current data does not show activity or strong activity Olverembatinib in positive AL. So I think that those 2 are based on the current clinical data, which Olverembatinib has advantage over those cinemas. And 11 turns first, the still early require RCT trial and approval by the FDA. And more importantly, I think that the lines were definitely the best and the most important 1 and the broad activity against all mutations. They early line I think we are doing the second line trial. We do have data, early data to support that. I think that the focus -- if you look at the current market this year, -- 2 of the second line actually is taking the most market share among the $7 billion annual sales, 2 of the second line has been consistently taken each about $2 billion annual sales, okay? Moving forward, I think currently, there's -- including the [ Selmec ], there are 5 drugs with the first-line label -- so for terms or any other compound tries moving into the first line is going to be heavy up hill bottle. And it also takes a long time and very costly. So I think our focus is really moving forward and also based on the data, it's probably one button would be the first choice of the TKI for the second line patients. So in that regard, we don't worry about the competition of the first line actually more first-line treatment, the patient will fund us through Olverembatinib in terms of the best second-line treatment.

Thank you. There are no further questions at this time. I would like to turn the call back to management for any closing remarks.

First, thank you all for attending and also very excellent insightful questions. This is a very timing in terms of our annual report for 2025, representing the first year, we are -- have a 0 engine for commercialization due to 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 the probably cornerstone product for hematology-oncology with our selective Bcl-2 inhibitor we are probably in a really best positioned in the global normal product development that not just being the first approval to commercialize in China in those products and indications. But globally, we are potentially best-in-class with clinical data in terms of safety, efficacy and also in the registration trial. I think that's a really unique position. At the same time, of course, there's a huge potential in terms of commercialization readiness in U.S. and also looking forward to our -- the partners for the global market expansion. So we are very excited with our strong achievement, the milestones transformation year for 2025, and looking forward, we are more excited to see all the reduction trial advance well, looking forward to have or be ready to have the commercialized in U.S. being the global leader in those therapeutic areas with the best-in-class potential for drugs for multiple hematology malignancies and looking forward to working with you all and all the investigators and the investors around the world to bring the best drug to benefit patients globally. And thank you all. Have a good day. Thank you.

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

Thank you. Thank you all.