Ascentage Pharma Group International

Good day, everyone, and welcome to Ascentage Farmers 2025 Annual Results Earnings Call. At this time, all participants are in a listen-only mode. After management's prepared remarks, we will open the call for questions. As a reminder, today's call is being recorded. Thank you for joining us. I will now turn the call over to Yuli Shen, Senior Director of Investor Relations for the Safe Harbour Statement Yuli, 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 full discussion of these risks, please refer to our filings and disclosures. On today's call, I am joined by Dr. Da Junyang, 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. Xiaomeng Wang, co-founder, chief scientific advisor. Dr. Qu Chao Si, head of commercial. I will now turn the call over to Dr. Yang.

Thank you. Good morning. I'm Daojin Yang, chairman and CEO of the company. Today, I'm very happy to present our 2025 four-year financial results and the corporate update. I will have the following agenda, business update, R&D highlights, financial results, and 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 total $82.1 million. Our year-end cash balance is about 353.2 million cash runways through 2027. I think in 2025, we are the first zero-listed biopharmaceutical company on Nasdaq following our Hong Kong Stock Exchange listing in 2019. We successfully raised approximately 322 $6 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 SOVA approval as a global first single-agent BCR2 inhibitor after BTK treatment in CLL and SLL. Gloral-4 phase III registration of trial received clearance globally, including FDA, EMA, and CDE. This is a truly unique opportunity as we are the global phase III registration trial in high-risk MDS, the only one in that phase III registration trial stage. Polaris 1, for the PH positive AIL, the phase III registration trial also received clearance globally, including FDA, EMA, and CDE. Part 1 data also reported at ASH demonstrated a strong 64% MRD negative CR rate in the first-line pH-positive AIL. Over-empatient have granted a breakthrough designation for the first-line treatment of pH-positive AIL by CDE. We are also really proud to have FDA and CDE IND clearance for our novel BDK degrader, APG3288. Both the server class and our martinib 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, IHA, and other conferences, and also we publish many peer-reviewed top journals. I think here's 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, Orvambactinib, as a novel third generation BCL-ABO inhibitor, and Lisovacast as the novel BCL-2 select inhibitor. Both have been marketed in China, and also entered four global registration trials, cleared by FDA EMA. In total, we actually have nine registration trial for multiple indications. We also have several novel, potentially first-in-class compound targeting, such as FAK ALK ROS1 triple kinase, and MDN2 PV3, the dual PCR2 XL, and the PRC2 third generation, like the EED inhibitor. And more importantly, we have newly cleared phase one novel BDK degrader, ABG3288. All of these are running the trials in U.S. and China and in multiple countries. Many focus on hematology oncology, but also have potential and also in the clinical stage testing indications such as anemia. So we have build a really large commercial scale in China with a dual product approved, especially for our BCR2 slash inhibitor. The subclass was ahead of our schedule last year. And with the two commercial product, we have built over 270 by the year end commercial team, covered 1,500 hospitals, and more than 800 DDP pharmacies. I think our dual engine strategy will go well as you can see our last year commercial revenue. I think that's a transition for our percentage from being rely on the investment, investors and also BD income to the last year 100% cells of the commercial stage of product. I think that that's a really important transition for a company to be able to self-sustain with our own revenue to support our own R&D program. If you look at just our botany alone, we have a strong cell following full NRDL listing covering CML with or without mutation. So if you look at the total cell, reaching $62.2 million, that represents 81% year-over-year growth. And it will continue to cover more hospitals, DTV Pharmacy, and also a broader reach to the Tier 1 hospitals. And with the full NRDR coverage, and also translating into very long DOT that will support or sustain the growth as the patient continues to use our drug over a long time. If we look at the Resolver class, first, this July approval was ahead of schedule, and we built a very fast and full-functional commercial team dedicated to the Resolver class. So the streamline go-to-market strategy using the national commercial infrastructure really helped us to rapidly expand the sales force and the hospital coverage. So just the first five months, we have reached more than 10 million US dollar sales. This is, I think, is among top at least in the hematology oncology product cells in the first couple months in China. And then let's go to the R&D highlight. First, let's look at our NISTOPO class is actively advancing its global phase three registration of trials. First, our approval as a single agent, For CLSL, after BDK inhibitor is really represented the first label for the BCR2-select inhibitor. As you know, Venetocast was approved 2016, and continually, the only single agent was limited to the 70P-DELETE CL and SL. The other CLSL is all combination with the CD20 antibodies. Our Glora 2 and Glora 3 also received FDA EMA and CDE clearance. And more importantly, I think that the Glora 4 is the first-line high-risk MDS in combination with the AZA or without the AZA cytodine control arm. Both received the FDA EMA and the CDE clearance will continue pushing forward all these important global phase three registration trial. I want to share a few important clinical data with you. First, with the single agent approval, based on the CC201 registration study, those patients actually have much poor baseline characteristics. First, the CD actually give us a very high bar about four or five years ago required all these CRS patients have to fail both the BDK and the CD20 antibody-based therapy. Many of them have a high-risk, complex cryotype, and also many have multiple mutations. So we achieved a really good efficacy as a single agent and demonstrate a favorable safety profile. If you look at other key data in the AML and the MDS, actually this is primarily US and Australia data with the leading PI from the US and this actually has presented both at ASCO and ASH. If you look at our ORR as a combination with the AZA, in the naive, newly diagnosed AML patient, we achieved the ORR 83%. And more importantly, in some cases, about 22 patients who have failed the class, we also achieved 32% ORR. In the MDS, we have a In the newly diagnosed, 80%, and in the second line, RRMDS, we have 50% ORR. I think based on those excellent data and many other clinical data, FDA gives us clearance to conduct global phase 3 registration trial as the first line for the high-risk patients. MDS, and this has been cleared by FDA, EMA, and CDE, actually among close to 20 countries regulatory agencies. So we are actively enrolling patients in U.S., Europe, China, and throughout the world. So if successfully carried out, the SOVA can become the first VCR2 inhibitor for the treatment of first-line high-risk MDS. This is really a global and mathematical need. Actually, there's no target therapy approved in the last 20 years. And current therapy have much poor efficacy. And five years survival rate for high risk patients is only about 16% to 24%. We are also really proud of these global efforts, leading by Dr. from MD Anderson and Dr. from Peking University People's Hospital, and many, many excellent experts and PIs for MDS around the world. Based on the public information, we want to highlight few key difference 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 very similar patient population, including those in China. So if you look at the SAE incidence, it's much higher for venetoclasts or serendoclasts. And the infection rate is also significantly higher. So that's consistent with clinical observation that the serendoclasts have a better safety profile, better tolerance, and more importantly, we have a better drug compatibility. CLSL patients often are elderly and immunocompromised with frequent infections. Commonly used antifungal drugs are strong 3A4 inhibitors, but does not affect our Resveratrol class PK. So if you look at the PK variability in combination with some strong 3A4 inhibitors, I think that the impact for esophagitis is minimal. For other two drugs, either about eight times or 11 times need to be at the adjusted dose if they're combining those. That will strongly affect clinical combination studies. And also, if you look at the PGP or BCRP sub-trades or inhibitors, the subclasses are probably the ones that have minimal risk in those combination studies. No need to adjust those with many BDK inhibitors. I think that those are a very unique advantage for the subclass as the BCR2 selector inhibitor. I also want to highlight a few important progress made and a summary here for Oren Bartendip. Oren Bartendip 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 RCT also received FDA, EMA, CDE, and the PMDA clearance. So we are actively pursuing advancing the global enrollment. Polarization I is very important. This is the first time we got a clearance last year for the first-line pH positive ALL. And this is also cleared by FDA EMA and the CDC in China with a breakthrough designation. Part one of this trial, the same trial design data was presented at ASH. And you can see the data from 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% MRD-negative CR rate. This is almost double the same patient population for the pronatolib, which only have 34.4% MRD-negative CR rate. But this actually is among all the BCR-ABL inhibitors the best one. So we actually almost double the current best PCR-able inhibitor for the same patient population, and also demonstrate really well safety profile. Another data is looking at the potential second-line treatment for the CML-CP patients. This is all, again, presented at ASH last year. We can achieve more than 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 sustained remission with improved survival and much reduced non-relapse fatalities. Another potential treatment is really for the combination with our own . And in this case, it's actually in the pediatric patient population. That is a first-line regimen in the pH-positive L, demonstrate really excellent efficacy and the safety profile. I think that this would be really important for some of the patients to receive the chemo-free and the two already active agents with a long-term benefit. Orvartinib as a multiple kinase inhibitor also demonstrates clinical benefit for some rare hematological malignancies, such as this very hard-to-treat myelo-lymphoid neoplasm with FGFR rearrangement. And these actually take a while to recruit those patients, but most of them achieve an excellent response clinically. And then we continue to push our pipeline. In the interest of time, we only show one example as our novel BDK degrader, APG3288. This actually we receive almost the same time clearance by FDA and the CDE. And based on the preclinical data, I think we also did a comparison with B1 or Neurix BDK degrader, demonstrate good selectivity and potency. And we'll push forward this compound in US and China for multiple indications. I think that in summary, the subclass as a very safe and potent BCR2-select inhibitor. Some refer BCR2 inhibitor as a small molecule of KD1. That really means it has multiple indications and also opportunity for multiple combinations. But I think more importantly, we are probably globally the only company that has not just the BCR2-select inhibitor, but also Oren Bartendorf, representing the best third-generation B-cell elbow inhibitor, and the MDN2-PV3 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 multiple B-cell malignancies among many hematological malignancies. Lastly, I think I will turn the financial result to our CFO, Wei. Wei, let's go to the slide number 28. Thank you, Doug, again.

Yeah, thank you so much. Yeah, 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. Yong, and centered on olivarambatinib and lisoptoclax. Turning to olverambatinib and lisoptoclax individually, olverambatinib 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 Lasapta Clax, which was approved in July 2025, first five-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 ongoing that are expanding and moving forward. In addition, the increase in S&D expenses, sales and distribution in 2025 from US $27 million to $51 million was primarily driven for Salesforce expansion ahead of commercial launch of Lesoptoclax, which is an efficient use of capital. So 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 Lasaptoclax approval, raising combined proceeds of US $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, Huy. So I also want to present our clinical catalyst and the milestone for 2026. On the clinical development side, our major focus will be advanced enrollment for the GLORA and the GLORA4 registration trial, and also advanced enrollment for Olinvac-Tinnock 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 a complete enrollment and then be able to file NDA in 2027. We'll continue to push The greater APG32-ATA global phase one study in terms of safety, tolerability, PK, and potential efficacy data. And then also advance our ED inhibitor, APG591A, 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. but I think that the major in terms of milestone for the clinical development are those highlighted here. On the commercial front, we will continue to drive the sales growth for Orambartinib and also the server class to the tier one hospitals and more pharmacies. And for the server class, we will do our best for the benefit of patients, especially CRSL, 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, Orinbactinib and Liserva class. 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 the proven track record of translating the clinical development into the novel commercial product, and advancing our best-in-class potential therapeutics in global ratification studies, I think with the dedication and the effort from all our team and also our collaborators, And the PIs around the world will really moving our pipeline to addressing the global medical need, making a to become the global leader in these therapeutic areas. Lastly, I think with the patient-centric innovation and global breakthrough therapies, and with currently seven, we'll call the seven magnificent, seven active compounds, small molecule drugs in active clinical trials addressing multiple hematology malignancies from the CML, ALL, to CL, AML, MDS, multiple myeloma, and potentially some of the lymphomas. and anemias hopefully with all your support we can make 2026 another successful year for a percentage thank you all for your attention and now we'll be happy to answer any questions you may have thank you thank you we will now begin the question and answer session to ask a question please press star

then one, one on your telephone keypad. We will take our first question. The first question comes from the line of Brian Cheng from JP Morgan. Please go ahead. Your line is open.

Hey, guys. Thanks for taking our questions this morning. Dr. Yang and Lisa, good to chat with you. Maybe just first, you know, Dr. Yang, you talk about how this year is really about enrolment, enrolment, enrolment. Can you give us a bit more color on, you know, where you are in terms of enrollment for your registrational studies, especially the GLORA4 study in MDS with lisaptoclax and also the Polaris 1 study in case-positive ALL? And, you know, related to those indications, how should we think about the next data milestones, you know, at the upcoming medical conferences later this year?

Thanks. Thank you, Brian. Very excellent question. I think let me maybe address these two parts. First, for the Glora IV MDS, high-risk MDS, we are very happy to see this Phase III registration trial protocol receive a clearance by not just the FDA, EMA, CDE, and also among close to 20 countries' regulatory agencies. And this is the first-line treatment for the naive, treatment naive newly diagnosed high-risk MDS. And more importantly, this is now really the only phase three regression 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 enthusiastic for this clinical trial to help patients globally with the MDS. And with the Polaris-1, this is the first-line pH-positive ALL. As you know, we also presented part one of the same protocol data at ASH. The three-month MRD-negative rate CR is 64%, almost double. on the same patient population, about only 34%. So I think that those two registration trials are 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 two first-line treatment, and you can see MBS We are the only one front runner in the phase three radiation trial globally. There's almost no competition there. The Polaris One is the first line for the Ph.D. positive AL, also with excellent data, potentially the best in class for the Ph.D. positive AL 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 One only requires three months MRD negative CR rate as a primary endpoint. And also, we have a strong support from FDA and all the regulatory agencies to support a protocol of the Glora IV. Overall, we will do our best to achieve complete enrollment, and with the current timeline and the primary endpoint, we anticipate, 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 in 2027.

Got it. Ben, maybe just one more. Just how do you think about the commercial growth opportunities for both OpenBandNet and the SantaClex 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. Thank you.

Yeah, maybe for the commercial part, we can have our head of commercial Jichao, to address the part of your question first.

Yeah, OK, 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 our investment, which really benefit from the broader reimbursement support affordability. after NIDL 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 hospital and D2C pharmacy access with more than 800 hospitals and D2P pharmacy, which significantly improved the accessibility by the year end. which also included more than 355 a hospital with formula access you know hospital listing is very important in china market and third i believe if you look at the the sata class which was uh approved in china and since july and we got sales for five months and this other class uh i mean really give us a a second growth engine up to launch and generating uh uh more than 70 million RMB in the first five years on market. And fourth, I think we scale their commercial organization and Dr. Yang and Dr. Witt both mentioned, we scaled up our commercial organization and meaningfully our team actually almost tripled compared to 2025 compared to 2024. And this commercialization team growing to more than 270 people and then converting more than 1,500 hospitals nationwide. I believe that's the key drivers for the last year's commercial growth. Thank you.

Great. And 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? And then as you think about your phase one study, What would be good to see from this initial phase one?

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 very thorough, of course, as currently preclinical data to compare our BTK degrader with B1 or Neurix. I think based on this comparison, we selected our candidate compound moving into the phase one. 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 as the BTK is a validated target, the BTK degrader can take care of many of the BTK inhibitors Covalent non-covalent mutation or not basically have a broad advocacy in the oncology space I think I'm mostly unique for a percentage of Once we go through the phase one, typical safety, colorability, PK, and some signal of advocacy with the potential RP2D, we'll probably move very quickly into the potential single agent indications for the fast to market approach. The second part, I think, is unique in the sense that we have a very excellent BCR2 selective inhibitor. So the combination of BDK inhibitor or degrader and the BCR2 inhibitor could really offer some of the hard-to-treat patients benefits. And in the case of the CLSL, At least with the fixed duration, it's really a potential, even some case, clinical cure. That means there's no progression after five years treatment, I mean stop treatment. I think that that will also offer additional benefit, especially for the young patient with the CLSL. in combination with the BCR2, maybe also can treat some harder treat like DL-BCL. I think thirdly, I think also at least a part of our moving forward strategy potential, the maximum return is that there are also many non-oncology indications for the BTK degrader, like autoimmune diseases. I think with all those three reasons, We are really looking forward to full speed to push this novel BDK degrader into the clinic development and many other potential combinations and indications.

Great. Well, thanks for the call and thanks for taking our questions. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Byron Amin from Piper Sunder. Please go ahead. Your line is open.

Yeah, hi. Thanks for taking my question. Maybe to start, for olirambatinib, what is your market share in China versus eskiminib and panatinib? And which CML patients are you seeing the most adoptions? And then I guess, you know, for second half 2025, sales grew by about 7% versus first half 2025. What can we expect for the growth rate for overrun batinib in 2026? Thank you.

Very good question. 2025 was the first year for the NRDL coverage, and especially for the with or without mutation. So the patient population compare our first approval indication with T315 mutation only, the patient population more than tripled. That's number one. The NRDR 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 the province, the reduction payment can be reduced by 90%. So that's really significant as this patient's taking the drug in a long time, right? Very good long DOT. So the NRDL coverage in China for the CML patient, we see really benefit important benefit. The patient population in China, as the other lay line treatment, like you mentioned, Acinimib or Panadolib, both were only approved last year. They don't have any establishment or the data from China. We also have, you know, last three, four years market use, even though it was more dedicated mutation patient population. But overall, the physicians and the patients are really well-educated position once they get into the full NRDR coverage. For the both cinnamus and prolatenib, they were not under NRDR coverage, okay? So that also limits the use of those two drugs, only got approved a year ago. So there's not really much stealth affordability for those that are not covered, the Asinamibs or Ponatinib in China. Moving forward for 2026, we see the benefit of NRDL will continue as the price is good for two years. And if we just look a little bit next year ahead of NRDL renewal, we're also really confident as the new policy from the NRDL is to maximize the support for the novel agent and also those un-mathematical needs. I think this is one of the examples falling into the category with strong support by the NRDL. And also, we currently, another important indication, also a very high prevalence disease is the pH-positive ALL. In the real world, we do have many pH-positive ALL patients benefit by the Orn-Bartender. But at the same time, because they are not officially into the NRDL coverage, So currently, in those patient populations, we still want to finish our registration trial, be able to get into the NRDL. So moving forward, I think there's a continued expansion and growth of the revenue for all martinib in China, both the CML and the PHE-positive ARL.

Thank you for that, Dr. Yang. And maybe just a follow-up. Clearly, you know, there's a lot of focus on the CML treatment landscape, especially, you know, yesterday Merck announced acquisition of TURNS for $6.7 billion. How do you think olivarumbatinib 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 ovirambatinib and lisaptoclax can we expect to see data in 2027? Thank you.

Great. Really excellent question. And actually, we're all very excited to see the acquisition of the terms by Merck with obviously a 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? So to be honest, a couple of years ago when we were developing over-impertinent, there are some concerns from the investors that maybe this indication is small compared like a lung cancer, breast cancer. But if you look at the history, The first generation, the Imatina, the Gleevec, actually just in the CML alone, the peak sell before pattern expiration is almost 5 billion peak sell annually. So I think overall, the current CML market globally, the peak sell is about, I think the total annual sell is about 7 billion. And Ascent Image last year already reached more than 1 billion sales. So I think that there's an estimate, the potential, just the CML global market, the pixel can reach over $14 billion. So I think this is also supported by the Merck acquisition of Terns, primarily for the CML drug Tern 701. So 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 very happy we entered the option agreement with Takeda about two years ago, June 2024. I think globally, Takeda will be our partner. I think, as you know, in the CML and AL space globally, Takeda is really one of the leading companies, aside from Nomartis. I think Takeda will be our strong, the best commercial partner for Orinbactinib moving forward. The third part of your question is about the registration trial of the two drugs, right?

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

Yeah, I think we currently push it forward really full speed for the best effort for the GLORA4, the high-risk MDS registration trial, and also both Polaris 2 and Polaris 1 for the over-martinib. I think the Polaris 2 or Polaris 1, Polaris 2 is a six-month MMR rate after the last patient for the potential accelerated approval. And the Polaris 1 is a three-month MRD-negative CR rate. So I think once we complete enrollment, those two most likely would have an opportunity to file the NDA in 2027. The GLORA4 actually also has a good chance because we enroll patients very fast, as in this indication with the BCR2 inhibitor. We are the only registration trial globally for high-risk MTS because many drugs failed, including Verna trial was inactive. So we do see a very strong interest and a very good enrollment in that space. And with the current protocol achieved, I think this is, in my 20 years of drug development record, is really the first time for the registration trial of the same protocol, you know, approved, cleared by multiple regulatory agency in the same indication. As you know, in our CLL, we actually did three different registration trials. because of different landscape and the different regulatory requirement. So I think we're very happy to see the GLORA IV registration trial enrollment is actually really promising, and we're potentially also looking forward to have the NDA funding in 2027.

Perfect. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Gregory Renza from Tourist Securities. Please go ahead. Your line is open.

Hi, Dr. Yang and Advantage 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 Oberlin Badanib's profile relative to particularly around the, you know, the 24 weeks or six months MMR rate, you know, with your existing data. And then just as a follow-up, so on, I know you have a policy to study going, but just curious about potentially expanding, you know, into second line, earlier lines in CML. What's the progress on that one? Thank you.

Thank you. Very good question. Obviously, we are very happy to see TURN's acquisition, and also 11 data presented at ASH last year. But I think O1-Bactinib will really have a unique advantage based on the clinical data. So we probably have the same ATP binding inhibitor as 11, and TURN is more like a cinnamix. as an allosteric inhibitor but do remember both the drug are in phase one or phase one two slash and but they have a lesson much less than a patient number compared to own bartender and this is based on current data there are less than hundred and also The dose in terms of the RP3D or registration trial has not established for both drugs. And at least based on the current published data, it's not clear they're working on any gatekeeper mutation, T3155I, or those with compound mutations. is not reported, or based on the assignment data, require five times dose for those with TC15 mutation. So clearly, there's no long-term safety data or efficacy data, and there's no also report on any efficacy in the pH positive. And specifically, if you look at the, you mentioned like MMR rate, I think one is much less the 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 the US primarily was the PIs from the MDNS and others. were heavily pre-treated. They are representing the CML patient of fourth or fifth line, and one third of them has a T3-1-5 mutation. So I think that you know all the BCI-able inhibitor, either kinase inhibitor or allosterone inhibitor, the responses really depend on the patient baseline characteristics. How many, you know, prior lines treatment and mutation profile. So I think that they, of course, this is not hard to have comparison, but just with the current data, I think we really demonstrate very broad, very potent activities and also long-term safety profile and the efficacy as well. So another thing I think for both drugs, especially under the Project Optimus, FDA would require Tern's compound and others have to do the RCT, right? They have to do the RCT trial to get approval. And in that case, they also must have a control arm. So it's hard to see what would be the control arm, but these are definitely required based on the Project Optimus. the optimal dose in terms of safety, efficacy, and the RCT design and the control arm. But I think overall, we are really confident, especially with our partner, Takeda, we're gonna position well for the ley line, CML, for those with mutation, and also very active, excellent data in the PHS-positive ALL. And we already conducted 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 all intolerant. So I think we are really confident we will benefit the patient for those early line as well. But of course, we will conduct the more studies, especially after we complete the redactation trial for ovarian bartender.

Got it. If I may squeeze in one more. Lisa has really strong start, you know, following five months of launch. But we know that V1 has that PCL2 inhibitor just approved recently as well. Just curious how that would play into dynamics for Lisa's uptake in 2026. Thank you so much.

Yeah, I think that in China, we were the first domestic BCR2 inhibitor commercialized last year. So we were at least six months ahead of B1 surrender class approval in China. That's number one. Number two, I think based on the current data safety, And also another thing is the Sorento class dosing up is similar to another class, weekly dosing up. And the starting dose for Sorento class is actually one milligram. And the approval dose is 320 milligram. So from one milligram to 320 milligram, and with five different dose strengths, and take nine steps, okay, to do the dosing up. I think that that's really, you know, not convenient for patients with the CLL and the SL. And also, if you look at the overall safety profile of the SAE, even some of the deaths in that registration trial, and the infection rate is so on, the subclass is probably the best among the currently three on market, the BCR2 inhibitor. And actually, this on the publisher, the drug label, surrender class actually have even worse DDI risk among the three drugs. So I think we are confident that we'll continue to do well and expand commercial sales coverage and also especially the registration trial among globally for the MDS. And also our Glora2 and Glora3 are also approved by CDE and other countries. The Glora2 will offer the patients with CRL the first-line treatment in combination with Carla in a fixed duration. The 18-month fixed duration with the CRT as the control arm. I think that actually is doing well in terms of enrollment and the Glora3 is the AML and we are the also the first the only the AML registration trial approved by the the CD a year more than a year ago and currently active enroll and this is the same you know validated indication validated the protocol we expect will do well for both Glora to and a glossary in China and a few other countries and of course they both are not yet not for the US or Europe because they Control arm or because of the trial design, but I think to answer your question. I think Will do well not just because we are six months. I had approval for surrender class but based on the really a excellent drug properties and clinical data, as well as the multiple indications, we are more in an advanced position than the Sorento class in China or globally.

Thank you.

We will take our next question. Your next question comes from the line of Jeet Mukherjee from BTIG. Please go ahead. Your line is open.

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 there. 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 INI or CNS diseases? Thank you.

Yeah, 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. Our aim is to cover at least 80% of the cells potential. That represents probably around 2,000 hospitals. We already covered about 1,500 hospitals. 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 cell supports to cover the 80% potential cells. 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 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're not the first one, but it's not really too late. The first is there's a lot of, I mean, this is a validated target, and also the BTK Degrader to take care of many of the inhibitors, but it doesn't matter if it's a covalent or non-covalent mutation or not. That's one. Secondly, 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, CNS 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 confidence and see much huge potential for the VTK degrader in oncology and non-oncology, and also with our BCR2 inhibitor in terms of combination.

Thank you. Your next question comes from the line of Matthew Beigler from OTCO. Please go ahead. Your line is open.

Hey, great. Thanks, Dr. Young, 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, like, the 30,000-foot view question here is, like, 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. And do you think that that setup, or how do you think that setup plays to Ascension's favor here with BTK-degrader and lisaptoclax? Thanks very much.

Excellent question. I think obviously the BDK inhibitor is well-established for the CLSL globally, and the current inhibitor already generates NSLs more than $14 billion. So that's a huge benefit. But at the same time, as you pointed out, the CL, especially some of the young patients with the CL, they don't like to take either BDK or BCR2 inhibitor for the lifetime, right? So the fixed duration, especially the combination of the BDK, currently mostly inhibitor with the BCR2 inhibitor, really offer the patient another Option they don't have to treat take the drug lifetime, right? So the current data pointed out actually This is the combination BDK inhibitor primarily with the inhibitor offer a good benefit in terms of a really durable PFS over five years, right And the PCR2, our drug, Lisovacus, 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 the BDK 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 inhibitor issues, mutation or not. So I think our plan, and hopefully we can demonstrate that with the clinical data, is that the BTK degrader combined with the server class first is to offer the fixed duration and be able to have long-term benefit in terms of TFS. 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 CL patients. That's in the CL, SL space. Number two is from the BTK-degrader, I think another potential, especially in combination with the BCR2 inhibitor, maybe offer some hard-to-treat disease, like DL-BCL, or in the case of the BTK single agent, fail the patients, right? So one of our strategies globally is our GLORA trial. This is an add-on strategy. Because the single agent alone of VTK inhibitor or degrader, probably at least half of them cannot achieve the optimal response in terms of CR. So in that case, you combine with the VCR2 inhibitor, it 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 PFS. So I think the incentive is really in a unique position to having both the BTK degrader and the BCR2 inhibitor for those multiple indications. Appreciate it. Thank you.

Thank you. We will take our next question. Your next question comes from the line of Christopher Leao from Lucid Capital Markets. Please go ahead. Your line is open.

Thanks for the question and congrats on the quarter. Just wondering if you have any insight into, you know, 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, competitive product that's based on some of the anti-trust rules. And there are cases before that in the anti-trust issue that they may have to return the drug if there's that competition, the anti-trust issue. So the current agreement, but still is an exclusive global partnership. So basically, both Takeda and Ascendage 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 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 terms 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 access to the options as your question. So I do think that there is a benefit to both parties that will move forward, pushing forward full speed on the over-vertend of commercialization for the global market.

And for Lasataclax, 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. As I mentioned at the JPMorgan conference, we are open, flexible, ready to enter any partnership that will benefit, bring synergy with our product and also the complementary resources. commercialization on the large scale on a more global market. But of course, at the same time, we are within the timeframe of, you know, be ready commercialization in two years. And many of the experts in the commercialization is that you need to be minimal ready two years ahead of anticipate the commercialization. So 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 the U.S., our commercialization capabilities. They are not exclusive. They really work hand-in-hand, in parallel. I think either case will benefit strongly our receiver-class commercialization, at least in the U.S., and also through the potential partners, either U.S. or global. So I think that 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.

Thank you. We will take our next question. Your next question comes from the line of Michael King from Rodman and Renshaw. Please go ahead. Your line is open.

Oh, thanks for taking the question. I had a question about the allosteric inhibitors, and that was answered 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 in the allosteric inhibitors in the CML space?

Oh, okay. No, I think that the current data, first, Asinimax as allosteric is doing well, right? Last year, it sells more than a billion. And in certain countries, like the U.S., also received the conditional approval, I mean, accelar approval for the first-line CML. But the Terns Compound 11 do not have data, at least clinical data, to show the activity in terms of T3-15 mutation, the gatekeeper mutation, and those with T3-15 mutation plus other mutations, the compound mutations. So I think that they, I mean, of course, there's a pattern and safety issues. So currently, our strong competitor, to be honest, we consider as a sentiment. But they are not active in about 40% of the ley line CML, which require five times dose or five times the cost. And all the drugs, based on the current data, does not show activity or strong activity as an over-attentive in THC-positive AL. So I think those two are based on the current clinical data, which has advantage over those . And 11, in terms of first, they are still early, require RCT trial and approval by the FDA. And more importantly, I think the ley lines, we are definitely the best and the most potent one. and the broad activity against all mutations. The early line, I think we are doing the second line trial. We do have early data to support that. I think that 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 cells, two of the second line, has been consistently taken each, about two billion annual cells. Moving forward, I think currently there's, including the Selmex, there are five drugs with the first line label. So for Terns or any other compound, try to move it into the first line, it's going to be heavy uphill battle. And they also take a long time, and they're very costly. So I think our focus is really moving forward, and also based on the data, is probably 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 follow through to our bartender in terms of the best second-line treatment.

Thanks for taking the question. Thank you.

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 have a dual engine for commercialization due to the full-scale functional Salesforce and also the first time as a dual listed dual primary listed company on NASDAQ. So moving forward, we also see really strong confidence and broad potential in CML, ALL, and also really the probably cornerstone, you know, product for hematology, oncology, with our selective B-sharp 2 inhibitor. We are probably in a really bad position in the global novel product development that not just being the the first approval commercialized in China in those of products and indications but globally we are the Potentially best in class with a clinical data in terms of safety advocacy 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 the U.S. and also looking forward to our 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 redactation trial advance well. Looking forward to be ready to have the commercialized in US being the global leader in those therapeutic areas. with the best in class of potential 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.