Ascentage Pharma Group Inter Aktie

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 Yuly Chen, Senior Director of Investor Relations for the safe harbor statement. Yuly, 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 biopharmaceutical company on NASDAQ following our Hong Kong Stock Exchange listing 2019. We successfully raised approximately $322.6 million 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 milestones, these are the following examples.

First, Lisaftoclax approval as a global first single-agent Bcl-2 inhibitor after BTK 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 registrational trial in high-risk MDS, the only one in the Phase III registrational stage.

POLARIS-1 for the Ph+ ALL, the Phase III registrational trial also received clearance globally, including FDA, EMA and CDE. Part 1 data also reported at ASH demonstrated strong 64% and MRD-negative CR rate in the first-line Ph+ ALL. Olverembatinib granted Breakthrough Destination for the first-line treatment of Ph+ ALL by CDE. We are also very proud to have FDA and CDE IND clearance for our novel BDK degrader APG-3288. Both Lisaftoclax and Olverembatinib entered 2025 CSCO Guidelines. Multiple oral presentations at ASCO and ASH 2025.

We continue to lead in the global innovation for many of our products including multiple presentations at ASH, AACR, ASCO, EHA and other conferences. 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 BCR-ABL inhibitor and Lisaftoclax as the novel Bcl-2 Selective inhibitor. Both have been marketed in China and also entered for global registration trial cleared by FDA, EMA, and total, we actually have 9 registrational trial for multiple indications.

We also have several novel potentially first-in-class compound targeting such as the FAK, ALK, ROS1, triple kinase and MDM2-p53 and the dual Bcl-2/Bcl-xL and the PRC2 third generation like the EED inhibitor. And more importantly, we have newly cleared Phase 1 novel BTK degrader, APG-3288. All of these are running the trials in U.S. and China and in multiple countries, mainly focused on hematology/oncology, but also have a potential and also in the clinical stage testing in indications such as anemia.

So we have built a very large commercial scale in China with a dual product approved especially for our Bcl-2 Selective inhibitor subclass 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 DTP 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 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 Olverembatinib alone, we have a strong sale following full NRDL listing covering CML with and without mutation. So if you look at the total sales, reaching $62.2 million, that represents 81% year-over-year growth and we will continue to cover more hospitals, DTP 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 patients continue to use our drug over a long time.

If you look at Lisaftoclax, first, this July approval was ahead of schedule. And we built a very fast and full functional commercial team dedicated to Lisaftoclax. So the seamless 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 top, 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 Lisaftoclax is actively advancing its global Phase III registrational trials. First, our approval as a single agent for CLL, SLL, after BTK inhibitor is already represented the first label for the Bcl-2 Selective inhibitor. As you know, venetoclax was approved 2016. And continually, the only single agent was limited to the 17p deletion, CLL and SLL. The other CLL, SLL is all combination with CD20 antibodies. Our GLORA, 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 AZA or without azacitidine control arm, both received -- I mean, received the FDA, EMA and the CDE clearance, will continue pushing forward all these important global Phase III registrational trial.

I want to share a few important clinical data with you. First, with the single agent approval, based on the CC201 registrational study, those patients actually have a much poor baseline characteristics. First, the CDE actually give us a very high bar about 4, 5 years ago, required all these CLL/SLL patients have to fail both BTK and CD20 antibody-based therapy. Many of them have a high-risk complex karyotypes 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 newly diagnosed AML patients, we achieved ORR 83%. And more importantly, in some cases, about 22 patients who have failed venetoclax, 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 registrational trial as the first line for the high-risk MDS. And this has been cleared by FDA, EMA and CDE and 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, Lisaftoclax can become the first Bcl-2 inhibitor for the treatment of first-line high-risk MDS. This is really a global unmet medical need as there is no targeted therapy approved in the last 20 years. And current therapy have much poor efficacy and 5-year survival rate for high-risk patients is only about 16% to 24%. We are also very proud these global efforts leading by Dr. Garcia-Manero from MD Anderson and Dr. Xiaojun Huang from Peking 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 venetoclax or sonrotoclax. 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 incidence is much higher for venetoclax or sonrotoclax and the infection rate also significantly higher. So that's consistent with the clinical observation that Lisaftoclax have a better safety profile, better tolerance. And more importantly, we have a better drug combinability. CLL/SLL patients often are elderly and immunocompromised with frequent infections.

Commonly used antifungal drugs are strong 3A4 inhibitors but does not affect our Lisaftoclax PK. So if you look at the PK variability in combination with some strong 3A4 inhibitors, I think that the impact for Lisaftoclax is minimal for other two drugs either need to -- about 8x or 11x need to be adjusted dose if they are combining those. That will strongly affect clinical combination studies. And also look at the P-gp or BCRP substrates or inhibitors, Lisaftoclax is probably the one of a minimal risk in those combination studies. No need to adjust dose with like many BTK inhibitors. I think that those are very unique advantage for Lisaftoclax as the Bcl-2 Selective inhibitor.

I also want to highlight a few important progress made and the summary here for Olverembatinib. Olverembatinib is approved with full coverage by NRDL. We see excellent commercial coverage and the revenue growth last year. Globally, we are conducting POLARIS-2 for the CML and this single-agent study RCT with the bosutinib 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 Ph+ ALL and this is also cleared by FDA, EMA and CDE in China with a breakthrough destination. 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 registrational trial in combination with low-intensity chemo as the first line, we have achieved 64% MRD-negative CR rate. This is almost double the same patient population for the ponatinib, which only have 34.4% MRD-negative CR rate but this actually is among all the BCR-ABL inhibitors, the best one. So we actually almost double the currently the best BCR-ABL 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% 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 demonstrated in more than 64 patients with blast phase and also some serious cytogenetic abnormalities and complex karyotypes. And those patients did very well and also into the sustained remission with improved survival and a much reduced non-relapse mortalities.

Another potential treatment is really for the combination with our Olverembatinib. And in this case, it's actually in the pediatric patient population that is a first-line regimen in the Ph+ ALL demonstrated really excellent efficacy and safety profile. I think that this would be really important for some of the patients to receive the chemo-free 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 very hard to treat myeloid/lymphoid neoplasm with the FGFR1 rearrangement. And this actually takes a while to recruit those patients, but most of them achieve excellent 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 receive almost the same time clearance by FDA and CDE. And based on the preclinical data, I think we also did a comparison with B1 or Nurix BTK degrader demonstrate good selectivity and potency. And we're pushing forward this compound in U.S. and China for multiple indications.

I think in summary, Lisaftoclax has a very safe and potent Bcl-2 Selective inhibitor, some refer Bcl-2 inhibitor as a small molecule of PD-1, that really means it has multiple indications and also opportunity for multiple combinations. But I think more importantly, we're probably globally the only company has not just the Bcl-2 Selective inhibitor, but also Olverembatinib representing the best third generation BCR-ABL inhibitor and MDM2-p53 inhibitor and also the novel new BTK protein degrader. As you can see, each one of these is a single agent or in combination, have potential to treat a multiple B-cell malignancies among many hematological malignancies.

Lastly, I think I will turn the financial results to our CFO, Veet. 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 registrational 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 enrollment. I think we'll do our best to achieve a complete enrollment and then be able to file NDAs in 2027.

We'll continue to push Degrader APG-3288 global Phase I study in terms of safety, tolerability, PK and potential efficacy data and then also advance our EED inhibitor APG-5918 in both oncology and anemia. Of course, we'll continue to push other active compounds in clinical study in U.S. and in China as well. But I think 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 our Olverembatinib and also the Lisaftoclax to the Tier 1 hospitals and more pharmacies. And for Lisaftoclax, we will do our best for the benefit of patients, especially CLL/SLL, together to the NRDL coverage in China in 2026.

I think that the key driver for Ascentage 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 registrational studies. I think with the dedication and the effort from all our team and also our collaborators and the PIs around the world, we're really moving our pipeline to addressing the global unmet medical need making Ascentage 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, multiple myeloma and potentially some of the lymphomas and anemias. Hopefully, with all your support, we can make 2026 another successful year for Ascentage.

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, Dr. Yang,you talked about how this year is really about on enrollment, enrollment, enrollment. Can you give us a bit more color on where you are in terms of enrollment for your registrational studies, especially the GLORA-4 study in MDS with Lisaftoclax and also the POLARIS-1 study in Ph+ 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 in 2 parts. First, for the GLORA-4 MDS, high-risk MDS, we are very happy to see this Phase III registrational trial protocol receive clearance by not just the FDA, EMA, CDE and also among close to 20 countries regulatory agency. 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 III registrational 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 really enthusiastic for this clinical trial to help patients globally with MDS.

And with the POLARIS-1, this is the first-line Ph+ ALL. As you know, we also presented Part 1 of the same protocol data at ASH. The 3 months MRD-negative rate CR is 64%, almost double the ponatinib and the same patient population, about only 34%. So I think that those 2 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 2 first-line treatment, and you can see MDS, we are the only one front runner in the Phase III registrational trial globally. There's almost no competition there.

The POLARIS-1 is first line for the Ph+ ALL, also with excellent data, potentially the best-in-class for the Ph+ ALL patient population. So I think the enrollment are doing well. And even though those only initiated late last year, but we see so far very excellent enrollment and very strong support from the health care providers around the world. And POLARIS-1 only require 3 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 the protocol of the GLORA-4. I think the -- overall, we will do our best to achieve complete enrollment. And with the current time line and the primary endpoint, we anticipate to the best we can and then to be able release the top line data or complete enrollment and then be able to file NDA in 2027.

Got it. 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 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 broader reimbursement support, the affordability after NRDL inclusion, right, 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 DTP pharmacy, which significantly improved the accessibility by the year-end, which also includes more than 355 hospitals with formulary access. Hospital listing is very important in China market.

And third, I believe if you look at Lisaftoclax which was approved in China and since July, and we got sales for 5 months. And Lisaftoclax, 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 scaled our commercial organization and Dr. Yang and Dr. Veet both mentioned, we scaled up our commercial organization meaningfully. Our team actually almost tripled compared to 2025 -- compared to 2025 compared to 2024. And this commercialization team growing to more than 270 people and 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, 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 Degrader 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 very thorough, of course, currently preclinical data to compare our BTK Degrader with B1 or Nurix. I think 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 as the BTK is a validated target, the BTK Degrader can take care many of the BTK inhibitors covalent, non-covalent mutation or not basically have 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 for the fast-to-market approach.

The second part, I think, unique to Ascentage that we have a very excellent Bcl-2 Selective inhibitor. So the combination of BTK inhibitor or degrader and the Bcl-2 inhibitor could really offer some of the hard-to-treat patients benefit. And in the case of the CLL/SLL, at least with the fixed duration is really potential even in some case clinical cure that means there's no progression after 5 years treatment -- I mean, stop treatment. I think that will also offer additional benefit, especially for the young patients with the CLL/SLL. And in combination with the Bcl-2 maybe also can treat some hard to treat like DLBCL.

I think thirdly, I think also this 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 3 reasons, we are really looking forward to full speed to push this novel BTK Degrader into the clinic 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?

Really good question. The 2025 was the first year for the NRDL coverage and especially for with/without mutation. And so the patient population compare our first approved indication with T315 mutation only, we -- the patient population will 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 the province, the reduction payment can be reduced by 90%. So that's really significant as this patient is taking the drug in a long time, right, very good long DOT. So the NRDL coverage in China for the CML patients, we see really benefit -- important benefit.

The patient population in China as other late-line treatment, like you mentioned asciminib or ponatinib, both were only approved last year, okay? But 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 they get into the full NRDL coverage. For both asciminib and ponatinib, they were not under NRDL coverage, okay? So that also limits the use of those 2 drugs only got approved a year ago. So there are not really much sales affordability for those non-NRDL coverage, the asciminib 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 NRDL is to maximize the support for the novel agent and also those unmet medical need. I think Olverembatinib is one of the examples falling into the category with a strong support by the NRDL. And also, we currently, another important indication, also very high prevalence disease is the Ph+ ALL. In the real world, we do have many Ph+ ALL patients benefit by the Olverembatinib. But at the same time, because they are not officially into the NRDL coverage, so currently, in those patient population, we still want to finish our registrational trial, be able to get into the NRDL. So moving forward, I think there's a continued expansion and the growth of the revenue for Olverembatinib in China, both CML and the Ph+ ALL.

And maybe just a follow-up. Clearly, there's a lot of focus on the CML treatment landscape, especially yesterday, Merck announced acquisition of Terns 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 Olverembatinib and Lisaftoclax? Can we expect to see data in 2027?

Great. Really excellent question. And actually, we're all very excited to see the acquisition of the Terns by Merck with obviously, really good price, $6.7 billion in all cash. I think the positive side is really that means the CML market globally is actually quite big, right? So to be honest, a couple of years ago, when we were developing Olverembatinib, there are some concerns from the investors that maybe this indication is small compared like lung cancer, breast cancer. But if you look at the history, the first generation, the Imatinib or Gleevec, actually, just in the CML alone, the peak sales before patent expiration is almost $5 billion peak sales annually, right? So I think overall, the current CML market globally, the peak sale is about -- I think the total annual sales is about $7 billion.

And Asciminib last year already reached more than $1 billion sales. So I think there's an estimate the potential just CML global market, the peak sale 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 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 AL space globally, Takeda is really one of the leading company aside from the Novartis. I think Takeda will be our strong -- the best commercial partner for Olverembatinib moving forward. The third part of your question is about the 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 push forward really full speed the best effort for the GLORA-4, the high-risk MDS registration trial and also both POLARIS-2 and POLARS-1 for the Olverembatinib. I think the POLARIS-2 or POLARIS-1 -- POLARIS-2 is 6 months rate MMR rate after the last patient for the potential accelerated approval. And 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-4 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 registrational trial globally for high-risk MDS because many drugs failed, including VERONA trial was inactive.

So we do see a really strong interest and really good enrollment in that space. And with the current protocol achieved, I think this is -- in my 20 years of drug development record, it is really the first time for the registration trial of the same protocol approved, cleared by multiple regulatory agency in the same indication. As you know, in our CLL, we actually did 3 different registrational trial because of different landscape and different regulatory requirement. So I think we are very happy to see the GLORA-4 registrational 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 TERN-701, particularly around the 24 weeks or 6 months MMR 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 or earlier lines in CML. What's the progress on that one?

Thank you. Very good question. Obviously, we are very happy to see Tern's acquisition and also 11 data presented at ASH last year. But I think Olverembatinib will really have a unique advantage based on the clinical data, right? So we're probably the same ATP binding inhibitor as 11 and the Tern is more like Asciminib as allosteric inhibitor. But do remember, both drugs are in Phase I or Phase I/II and but they have much less patient number compared to Olverembatinib. And this is based on the current data, they are less than 100. And also the dose in terms of the RP3D or registrational 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 the gatekeeper mutation, T315I or those with compound mutations is not reported or based on the Asciminib data require 5x dose for those with T3151 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+ ALL. And specifically, if you look at the -- you mentioned like MMR rate, I think one 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 PIs from MD Anderson and others were heavily pretreated. They are representing the CML patients of fourth or fifth line and 1/3 of them has T315I mutation. So I think all the B-cell inhibitor, either kinase inhibitor, allosteric inhibitor, the response is really depend on the patient baseline characteristics and how many prior lines treatment and mutation profile.

So I think that the -- of course, this is not head-to-head comparison. But just with the current data, I think we really demonstrate very broad, very potent activities and also long-term safety profile and efficacy as well. So I think that the -- 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 will 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. So -- but I think overall, we are really confident, especially with our partner, Takeda, we're going to position well for the late line CML for those with mutation and also very active data in the Ph+ ALL. And we are -- we already conducted and 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 its 2 TKI resistant and all intolerant. So I think we are really confident we will benefit the patients for those early line as well. But of course, we will conduct the more studies, especially after we complete the registration trial for Olverembatinib.

Got it. If I may squeeze in one more. Lisa has really strong start following 5 months of launch. But we know that BeOne 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 BeOne Sonrotoclax approval in China. That's number one. Number two, I think based on the data, current data safety and also another thing is the Sonrotoclax dose ramp up is similar to the Venetoclax, weekly dose ramp up and the starting dose for Sonrotoclax is actually 1 milligram. And the approval dose is 320 milligram. So from 1 milligram to 320 milligram and with 5 different dose strengths and taken 9 steps, okay, to do the dose ramp up. I think that's really not convenient for patients with CLL and SLL. And also, if you look at the overall safety profile, the SAE even some of the deaths in that registrational trial and the infection rate and so on, Lisaftoclax is probably the best among the currently 3 marketed Bcl-2 inhibitor. And actually, this on the published drug label, Sonrotoclax actually have even worse DDI risk among the 3 drugs.

So I think we are confident that we will continue to do well and expand commercial sales coverage and also especially the registration trial among the -- globally for the MDS and also our GLORA-2 and GLORA-3 also approved by CDE and other countries. The GLORA-2 will offer the patients with CLL, the first-line treatment in combination with acalabrutinib in fixed duration. The 18 months fixed duration with the CIT as a control arm. I think that actually is doing well in terms of enrollment. And the GLORA-3 is the AML. And we are also the first -- the only the AML registrational trial approved by the CDE a year -- more than a year ago and currently active enroll. 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 of the control arm or because of the trial design. But I think to answer your question, I think we'll do well, not just because we are 6 months ahead of approval for Sonrotoclax, but based on the very excellent drug properties and the clinical data and as well as the multiple indications, we are more in advanced position than Sonrotoclax in China or globally.

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 really 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 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 will 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 Degrader to take care of many of the inhibitors, but it doesn't matter covalent or noncovalent mutation or not. That's one. Second is, as your question pointed out, the BTK Degrader, like some of the other BTK inhibitors that actually have more probably potential in non-oncology, some of the autoimmune diseases 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 BTK Degrader 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 questionnaire, like do you think the CLL market is heading in the direction of an all-oral time-limited therapy ala 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 Ascentage favor here with BTK degrader and Lisaftoclax?

Excellent question. I think obviously, the BTK inhibitor is well established for the CLL/SLL globally. And the current inhibitor already generate annual sales more than $14 billion. So that's a huge benefit. But at the same time, as you pointed out, the CLL, especially some of the young patients with the CLL, they don't like to take either BTK 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 at least 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, our drug Lisaftoclax having very unique benefit in terms of other inhibitors is that we don't have a DDI issue. We don't have a DDI issue with the 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 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 Lisaftoclax, first is to offer the fixed duration and be able to have a long-term benefit in terms of PFS. 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/SLL space.

Number two is from the BTK Degrader, I think another potential, especially in combination with the Bcl-2 inhibitor, maybe offer some hard-to-treat disease like DLBCL or in the case, the BTK single agent failed the patients, right? So one of our strategy globally is our GLORA trial is add-on strategy because the single agent alone of BTK inhibitor or degrader probably at least half of them cannot achieve the optimal response in terms of CR. So in that case, you combine with the Bcl-2 inhibitor will then offer the patient better response, deeper response and potentially in terms of fixed duration to stop the treatment with long PFS. So I think the Ascentage is really in a unique position to having both the BTK Degrader and the Bcl-2 inhibitor for those multiple indications.

Your next question comes from the line of Christopher Liu from Lucid Capital Markets.

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 option agreement, right? Because they have competitive product, ponatinib that's based on the antitrust rules. And there are cases before that in the antitrust issue that they may have to return the drug if there's that competition, the antitrust issue. So the current agreement, but still is exclusive global partnership. So basically, both Takeda and Ascentage are bound to have that partnership to work together. That's number one.

Number two, of course, they have to get either clear antitrust or to wait the patent expiration of ponatinib, which I believe is later this year or early next year. I think that with that patent expiration, then there's no issue in terms of antitrust issue. Thirdly, I think for your question, of course, first of all, we are already a partner. We are strongly bind 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 Terns for over $6 billion, I think there's no reason that we do not work together and maybe work together early in terms of exercising the option as your question. So I do think it is a benefit to both parties that we move forward, pushing forward full speed on the Olverembatinib 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 that 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 of the experts in the commercialization is that you need to be minimal ready 2 years ahead of 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-hand in parallel. I think either case we'll benefit strongly our Lisaftoclax commercialization at least in 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.

Your next question comes from the line of Michael King from Rodman & Renshaw.

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 the current data, first, asciminib as allosteric is doing well, right? Last year, sales more than $1 billion. And in certain countries, like U.S. also received the conditional approval -- I mean, accelerated approval for the first-line CML. So -- but the current compound 11 do not have data, at least clinical data to show the activity in terms of T315I mutation, the gatekeeper mutation and those with T315I mutation plus other mutations, the compound mutations. So I think the -- I mean, ponatinib, of course, there's a patent and safety issues. So currently, our strong competitor, to be honest, is considered asciminib. And -- but they are not active in about 40% of late line CML, which require 5x dose or 5x the cost. And all the drugs based on the current data does not show activity or strong activity as Olverembatinib in Ph+ AL.

So I think those 2 are based on the current clinical data, which Olverembatinib has advantage over those asciminib. And 11 Terns first still early, require RCT trial and approval by the FDA. And more importantly, I think the late line, 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 data -- early data to support that. I think the focus -- if you look at the current market share, 2 of the second line actually is taking the most market shares. 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 asciminib, there are 5 drugs with first-line label. So for Terns or any other compound try to moving into the first line is going to be heavy up hill battle and they also take a long time and very costly. So I think our focus really moving forward and also based on the data is probably Olverembatinib will 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 favor through to 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 really excellent insightful questions. This is a very timing in terms of our annual report for 2025, representing the first year we are -- have a Dual-Engine for commercialization, build a full-scale functional sales force and also the first time as a dual listed, dual primary listed company on NASDAQ. So 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 position in the global novel product development that not just being the first approval commercialized in China in those products and indications, but globally, we are potentially best-in-class with the 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 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 registrational trial advance well, looking forward to have -- be ready to have the commercialized in U.S. being the global leader in those therapeutic areas with best-in-class potential drugs for multiple hematology malignancies and looking forward to working with you all and all the investigators and investors around the world to bring the best drug to benefit patients globally. 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.

Here at the Guggenheim Conference. Here at the Guggenheim Conference. My name is Brad Canino. Happy to be sharing the stage for the next fireside with Ascentage. We've got Veet Misra here. Thank you so much for joining us, Veet.

Thank you for having me.

And maybe we can just kick off if you can give a brief overview of Ascentage and where you are today, core focus of the company, where you've got the footprint and what you see as really the key pillars of the strategy for the company.

Yes. Thank you for the question. So Ascentage is a public company, dual listed on both the NASDAQ and Hong Kong Stock Exchange. We're a global company, close to 800 employees at this point. We're a commercial stage in China with 2 novel products for oncology indications in hematology. And we're rapidly growing.

We have a pipeline of 7 disclosed compounds, including the 2 products I mentioned, each of them novel, best-in-class potential, spanning essentially the big markets in hematology. And we have an internal discovery engine as well.

In terms of the breakdown, the spread of employees, predominantly in China, but we have over 100 in the U.S. So China, it's discovery, innovation, clinical trial execution and sales. In the U.S., clinical trial execution, we have 4 U.S. registration studies ongoing. So the U.S. is going to be our global market hub, which we're going to be -- that's the next chapter of the company to -- in terms of its global expansion commercially.

Okay. So great overview of the company. You've got a decently large pipeline of products as well. Maybe introduce the marketed products and the late-stage pipeline.

Yes, certainly. So in terms of the marketed products, we have, firstly, a third-generation tyrosine kinase inhibitor called Olverembatinib, which is a third-generation TKI in a space that's gotten a lot of attention in recent months.

Essentially, this is a disease category where there's been imatinib in the space brought out by Novartis in 2001. There's been the need, which increased survival significantly, but there's been the need for additional TKIs to be brought to meet patient needs due to resistance. There's the gatekeeper mutation, T315I, which is about 25%, sometimes 30%, depending on the representative population of CML.

And then there is safety concerns that can arise in the near term or later term and intolerance issues. That has been the case of the second-generation TKIs. It's been a large pharma category. There is a worldwide unmet need for CML and also ALL, both in terms of the pediatric population. It's the #1 childhood cancer, including solid tumors and also spans adult and elderly population as well.

So TKIs have to be especially potent to address ALL as well. We're running a U.S. registration and a part of a global registration study in ALL. So we're excited about that. And then also, we have a BCL-2 inhibitor approved in China called Lisaftoclax. It's the second ever BCL-2 inhibitor to get approved ever since Venetoclax got approved by AbbVie in 2016. So it's been a 9-year journey getting that on to the market.

There's a competitor out there that has a BCL-2 inhibitor that got approved for MCL. And essentially, the characteristics of our compound are a daily dose run-up as opposed to weekly. And we also have not experienced with our compound DDI issues, which is a concern as it relates to the importance of combining with other agents, including namely BTK inhibitors.

I'll jump to BTK. We have a BTK protein degrader that we just announced in early January, a U.S. IND clearance for. We subsequently last week announced China CDE clearance. We have an exciting preclinical package of this BTK protein degrader. We believe it's quite differentiating versus our competitors, which we'll talk about more over time. And that yields a combination approach with a BCL-2 inhibitor, which we have obviously in-house.

So we feel like we have the -- the only company that has a third-generation TKI and a BCL-2 inhibitor, both of which we believe has strong best-in-class potential. And to answer your question about the rest of our pipeline, we have 3 multi-kinase inhibitors directed towards solid tumors, a range of solid tumors that we're carrying out.

And we have a discovery engine, as I mentioned. So we also are bringing forward a PRC2 complex inhibitor, which we call APG-5918 for now, directed towards both multiple anemia indications, including SCD, beta-thal and oncology where we've seen some companies recently go after sickle cell and prostate cancer using the same type of approach and have yielded exciting results, but -- and Pfizer has an EZH2 inhibitor, part of the same complex.

So there's really quite minimal number of players in this category as well. So this is kind of our banner approach in terms of commercialization, global clinical execution and bringing about additional novel compounds to bring forward in the pipeline.

Great. Maybe we'll drill into the BCR-ABL first a little bit more. I mean you mentioned in that intro, the mutation potency, the improved tolerability. Maybe give a bit more granular details around that differentiation compared to the marketed products and the clinical stage products that are competitors that are being developed.

Yes, certainly. So it's been interesting to see the attention onto the CML space, especially in the last year, maybe slightly more than a year. There's been a couple of companies. I guess I'd put ourselves in that category that are essentially addressing the unmet need.

Some people can view it as disruptive, maybe in the sense that it's been, as I mentioned, a large pharma category. The issue with the patients is eventual intolerance and resistance to second-generation TKIs. There's a drug Ponatinib by Takeda that's addressed a lot of the concerns of second-generation TKIs.

Unfortunately, it has issues as it relates to toxicity. We do have a relationship with Takeda as a lot of people probably know where they have an option agreement ex China as it relates to Olverembatinib. We believe that in itself is highly validating of our approach as a potential franchise extension strategy for Takeda.

So I think one really needs to focus on potency, efficacy and long-term durability. Our compound got conditional approval and eventually full approval in the NRDL in China starting from 2021. So we have a number of years of history over our competitors that are disrupt trying to be disruptors. I think that really matters.

I think people get caught the excitement of looking at data cuts, looking at the safety efficacy point in time versus the pharma company standard drug and essentially extrapolate from that. That's fine. There's nothing -- one has to, however, take into consideration in the landscape, who are the ones that are showing durability over time because that's what matters when dealing with CML, the name of the game is survival.

So we have now the benefit, especially being a drug that is approved in China, where our KOL IST network and relationships have also done effectively post-marketing studies. So we've done -- so we have -- actually, there's published data now out there in conferences that have shown and very high reputable publications, Nature Journal of Clinical Oncology, et cetera.

Long-term studies, 4-year, 6-year case studies of patients who have had multiple failures of TKIs. Often, they even rotate back to a drug that hasn't worked before. It's because there's limited options. And then you can see patients actually revert back to having MMRs when they have had declines due to resistance.

And in addition, and this is important as well, patients have converted from advanced CML, AP or BP, acute phase or blast phase where the overall survival prognosis becomes more and more poor, back to CP, which is the majority of the CML cases are CP. They're diagnosed most often as CP. But to actually get a very difficult-to-treat population to revert back, that's quite meaningful. So our competitors aren't even close to that point yet.

Also, we have -- since we have the benefit of having both the TKI and the BCL-2 inhibitor, we've actually in-house in one company. We've actually done studies and others have as well as investigators combining our drug with Venetoclax, which we can do with our combination with our proprietary compound and have shown patients can achieve deep MRD, so MRD-negative CR rates. And this is important because these patients can then be eligible for allo-HSCT, which means they can then go on to longer-term potential remission.

So these are the types of studies that are being carried out right now with our drug. And this is what you want to see in terms of the kind of the long-term durability of the drug. DOT equates to sales. That's why I think this has also been a market that's caught the attention of investors again. And we've shown this type of effect in ALL, which is, as I mentioned, a difficult-to-treat disease, unmet need.

Great. Now maybe you can speak a little bit about the POLARIS-2 study for CML. Design for that study, what you're going up against and what you think the bar is for success to make that a drug that is competitive on the global stage?

Yes. I think the design is a nice rational approach to show the safety efficacy profile of our drug versus. In this case, there's 2 parts to it. One is a -- has a control arm, Part A against bosutinib, Pfizer's second-generation TKI.

And then there's a Part B that's a single-arm only T315I mutants. So this study is a global study, including the U.S. and EMA. We are advancing enrollment this year. We look to have majority of the enrollment actually complete this year. So we'll give more guidance as to when the trial is going to be completed, but progressing well.

I would say that one of the things is that we feel like there's a good probability of success given the trial design going against bosutinib. The endpoints are 24-week MMR and then a longer-term 96-week MMR. So it's designed to truly show the go -- the FDA approvable endpoint, and EMA approvable endpoint.

And also will emphasize the potency, hopefully, in T315I. So not to -- given the experience in China and patients, post-marketing studies, as I articulated, there's papers out there, publications, 4-year, 6-year follow-up. We feel like this -- when looking at the totality, this design will get us a good outcome, hopefully. Yes.

Okay. Let's switch a little bit and talk about the BCL-2, Lisa. You have an approved indication in China for that. Maybe discuss that in detail. But then where do you see the vision for this product potentially globally?

Yes. So one thing I should mention though for the POLARIS-2, there's actually a crossover as well between bosutinib and our drug as well. That actually has helped to stimulate enrollment also.

Yes. So to answer your question, so the -- I think one thing to note in terms of the population that was approved in the registration study in China, it was a very deep challenged patient background population. It was a pivotal Phase II study that yielded approval. These patients had complex karyotype, almost half had -- were classified as complex karyotype. 100% of them had BTK exposure.

A majority of that group were actually truly intolerant, resistant to BTK inhibitors. In China, the characterization has to be precise. There is really no one wants to -- one needs to be very intellectually honest with the regulators there. So you can kind of take it at its word that these were truly pretreated resistant BTK inhibitor patients. And with that background, actually, we did get approval with, I think, a label that was better than the market anticipated.

The specific language was patients who have received at least one prior systemic therapy, including BTK inhibitors. And essentially, that language doesn't have the word resistant or refractory in it. So it's -- that allows doctors to prescribe [indiscernible] as a 1.5 line therapy, not a second-line therapy.

We've actually shown at ASH taken forward this patient population have demonstrated high ORRs and overall survival in this patient population, carried it forward. So again, we have the benefit of post-marketing in China that we can carry forward here. And we feel like that with a lot of the noise that was going on, it's still not fully resolved yet with China versus U.S., how much of that is valid.

We've been hearing that from other companies. I think we're more rational about that now and just kind of looking at the data where it is and not discounting so much what's going on in discounting data from China. These are now very extremely well -- and these have been for a while, validated by very strong reputable publications, PIs. So we'll -- and obviously, we're conducting global studies as well with the proper balance representation of patients from each part of the world.

Yes. And you offer a different dosing schedule than Venetoclax as well in terms of the ramp-up and everything. What's been the experience like that? Maybe talk to the Chinese experience, but also this has been used with some global investigators in clinical trials. How do they see that different from Venetoclax? And what's the positive aspect of that? And how is your drug exclusively able to deliver that?

Yes. So the dosing matters. This is a community oncology physician setting compound. So consistency as it relates to -- we've seen some inconsistency from competition as it relates to what is the -- ultimately going to be the multi-week dosing schedule for their drug.

For us, it's clear. We have a 6-day daily dose run-up. So that is important for safety when you think about CLL and SLL and then other indications as well, such as AML, which is obviously has a high mortality rate.

And then obviously, we're going after an area, which is a big opportunity for us, high-risk MDS. There's no other company that's doing a Phase III registration study in this disease category. It's a multibillion market opportunity. And we are conducting a global study in HRMDS.

In addition, the other aspect that's important is DDI, drug-drug interaction, because the combination with the BTK inhibitor or a protein degrader is definitely going to come into -- it's already in play with the inhibitor, but now the big push is for fixed duration therapy. So obviously, you want to have elimination of DDI issues, but we're the only ones who definitively have shown there's no DDI issues with our compound. So that's going to be interesting especially as the BTK protein degrader becomes more and more high profile.

And then when you think about supportive care as well, like antifungals, that's where DDI also comes into play. And then, of course, the other area is bone marrow toxicity. So this has enabled us to really push forward in HRMDS. Venetoclax has shown years prior inability to treat multiple myeloma due to 2 Phase III studies showing bone marrow toxicity.

And then subsequently, as the more details came out last year during SOHO in HRMDS. So -- and as far as we know, another competitor with a BCL-2 inhibitor is not going after HRMDS,'re going after MM. So this is ours, to be frank, with HRMDS, a great opportunity for us. And then one can only go after this type of category with all those characteristics intact.

Yes. So let's talk about MDS for a bit. You've got the GLORA-4 study. Venetoclax did have a study that was unfortunately not successful. What is the rationale for bringing your drug there given it's the same mechanism? Maybe how does the differentiation play into that? And what are the key elements of that trial design that we should be paying attention to?

Yes, it's a really good question. So that VERONA study you're referring to with Venetoclax and HRMDS, the design was VEN Plus, an HMA, Hypomethylating agents, in this case, AZA versus AZA. And it's been -- it was known for quite a while leading up to the actual full disclosure of the results that the trial failed.

And we were embarking on the same design as well, as you mentioned, the GLORA-4 study. It was a little bit like we're on the edge of our seats, and we're getting a lot of questions about like what exactly went wrong in that VERONA study because you're going doing the same design.

Well, then finally came out during SOHO that the design of that trial was a double-blind randomized placebo-controlled study. And what occurred was there was early in the study, a withdrawal of drug in the active arm, early in the study. And in this case, it was AZA because you -- the investigator could only pull back on the known drug. But it essentially confirmed our position all along that it was the toxicity of Venetoclax. The hazard ratio was 0.908. So it wasn't even the near miss.

And unfortunately, the survival curves kind of both converged, both arms at 22 months. So it's, however, validated our approach, and we're really dedicating a lot of our resources to push enrollment.

The other thing about GLORA-4 is we have a dual primary endpoint. So the longer endpoint, of course, of overall survival, but we also have complete response rate as an endpoint -- primary endpoint, which could be the basis for accelerated approval, we'll see depending on the results.

Okay. Great. Maybe in the last minute or so, if you could just talk about across the portfolio over the next 12, 18 months, what are the top catalysts and milestones that investors should be focused on with everything you've got going on?

Yes, exactly. No, for sure, like pushing forward on the registration studies, as I mentioned, POLARIS-2, POLARIS-1, GLORA, we didn't really talk about that, but that's a combination with BTK inhibitors and then GLORA-4, so pushing forward. This will -- is our foray towards commercialization in the U.S.

And then also as it relates to the early-stage pipeline, a lot of attention now brought towards the PRC2 complex, EED inhibitor.

So Phase I results in that as well as the BTK protein degrader, giving more in due course, the differentiation, specific differentiation of that versus our competitors. So we've seen for both those cases with comparables that early small -- really small patient sets, ultimately, you need to have the right number to show safety, efficacy long term to instill confidence.

But you can see how even small number of patient sets can really move the needle in terms of value creation. So we're definitely allocating the appropriate resources for those as well to give the public more data. So that's been our push, and we're essentially well capitalized at this point, and I think have good optionality.

Okay. Great. Well, Veet, thank you so much for sharing the story. Thank you. Thanks, everyone, for listening in.

Thank you, Brad.

Good afternoon, everyone. Thank you so much for joining us for another session at the 44th JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here at the firm. On stage, we have Ascentage Pharma. I'll now pass the mic to the CEO, Dr. Dajun Yang, for a short presentation, followed by a live audience Q&A. Dr. Yang, welcome. The stage is yours.

Thank you. Really honored to be here at the main conference presentation for the first time. And we were supposed to do our presentation last year, but due to the planned IPO immediately after the JPMorgan meeting last year, so we had to cancel our presentation last year.

So it's a great honor to be here. And this year, we have made a lot of progress. And as I said, we did a great IPO last year following the JPMorgan meeting and also led by JPMorgan last year as well.

So this is really the overview of Ascentage. For some of you who may not know us before, let me go through this in a little bit more detail. Ascentage actually founded about 16 years ago, in 2009, and we are really truly global and commercial stage hematology/oncology company. We have 2 novel commercial products targeting BCR-ABL and also Bcl-2. We are one of the few dual listed on NASDAQ and the Hong Kong Stock Exchange. And up to the last financial report, we have $420 million of cash. So that will -- can support our current R&D plans through 2027.

We have a very robust pipeline. We have 7 novel active clinical stage compounds targeting more than 10 indications, with about 30-plus FDA-cleared INDs, and we actually received 17 orphan drug designation by FDA and also by EMA, 4 Fast Track designation, 2 of them are pediatric. We run at the time, more than 40 clinical trials globally. I think one thing really makes Ascentage standing out is that we have global IP protection over 478 global issued patents, about 500-plus more pending applications. We publish regularly on JAMA Oncology, Clinical Cancer Research, among other peer-reviewed journals globally.

Currently, we have close to 800 employees worldwide. Overall, we did or ongoing 13 global registration trials, including 4 FDA-cleared Phase III registration trials. Company is incorporated in Cayman Islands with headquarter in China, Suzhou, Rockville, Maryland and also Sydney. This is actually our headquarter in Suzhou building, the R&D center. So these are 2 novel commercial stage products with global opportunity. Olverembatinib is the third-generation BCR-ABL inhibitor approved in China for CML-CP with or without mutation and about 2 TKI, including the intolerant. And we are running 2 global Phase III studies cleared by FDA and EMA.

On the right, we have Lisaftoclax, the novel orally active selective Bcl-2 inhibitor approved just 6 months ago in China for the CLL and SLL after BTK therapy. I think for this indication, we are actually the first one globally after BTK in CLL with a single agent as Venetoclax was only 17p at deletion indications. We also have 4 global registration trials with 2 cleared by FDA and EMA.

We also have 4 global registrational trials with 2 cleared by FDA and EMA. This is our really the world-class innovative and a highly derisked late-stage pipeline. As you can see, the first 2 are commercial stage, targeting the variety of heme malignancies. We also have 3 other novel compounds potentially the first-in-class, these were successfully developed to the market. Those focus on FAK, focus on MDM2-p53, Bcl-2, Bcl-xl. There's no currently approved product yet globally.

I think there are also 2 exciting programs targeting the PRC2 through the EED, have potential both for oncology anemia. Just about last week, we announced clearance of BTK degrader cleared by FDA for the global study.

Here's a little more information about the Olverembatinib, HQP1351. As you can see, we have this product approved in China since 2021. That's why I said it's highly derisked. We already treated over tens of thousands of patients, CML with and without mutation and also Ph+ ALL. We have 3 global programs, POLARIS-2 targeting the CML with a single agent with the control arm bosutinib cleared by FDA and EMA and also POLARIS-1, first-line Ph+ for ALL patients. This is actually a great result. With the Part A of POLARIS-1 data we presented at ASH just last month, we doubled the 3-month CMR rate over like ponatinib in the same patient population. And we also received breakthrough designation by CD.

We also have one small indication targeting SDH-deficient GIST. This is a monotherapy for pivotal registration trial. And this is a group of patients which has no effective therapy globally. I think really exciting to see is that even that this is a conference where there are at least 2 other peer companies are targeting the same like a CML patient population received great attention at Street.

So overall CML market currently is over $7 billion or $8 billion and asciminib peak sales already increased from $3 billion to $4 billion. And Olverembatinib is strongly positioned for T315 mutation and compound mutations and could be the first choice for the late-line CML globally. There's another indication is the Ph+ ALL. It's very prevalent in Asian countries as China, Japan. Currently, there's no effective, safe small molecule drug and Olverembatinib is a global registration in the first-line Ph+ for ALL.

I think the data so far in the last almost 10 years development in the clinic with the 2 guidance that we entered, NCCN guidelines and also CSCO in China. I think you can see we have a really truly differentiated efficacy profile as a single agent. We show strong -- also really safety profile in Ph+ ALL patients. The longest time patients use our drug is almost 10 years since the Phase I in 2016. And we have a 5-year follow-up for the CML patients after Phase I and also about 6 years follow-up for those in the AP patient population. And we actually had several presentations at ASH last month with strong activity in other rare disease like [ MM ], also FGFR rearrangement, CML, VP, et cetera.

So basically, Olverembatinib demonstrates strong activity, especially in this slide, leading by the Dr. Kantarjian and Dr. Jabbour at MD Anderson. This is actually all U.S. patient population. The initial result already published on the ASH and JAMA Oncology. As you can see in this heavily pretreated, truly failed resistant CML patients, those who failed ponatinib, who failed asciminib and also over 30% of them have [ T31 ] mutation, okay? This is a really different patient population, as you see from some of the peers presentation at ASH or this conference.

So with this heavily pretreated then almost the last line after 4, 5 line patient population, we see a greater efficacy as a single agent. You can see that in those who failed ponatinib or asciminib, will receive a single agent about 40% or 30% MMR rate. There are few patients actually fail both, ponatinib and asciminib. We still see the single-agent benefit.

I think another very exciting data is what we released last month at ASH that in the Ph+ ALL, the newly diagnosed patients, this is part A of our global Phase III trial, the POLARIS-1. As you can see, in this population patients, we can have 64% MRD-negative CR rate, okay? This is almost double the same patient population ponatinib did about 34%. Of course, the control arm, the imatinib only can do about 16%, 17% CMR rate. We also have demonstrated very good safety profile.

Another exciting data is really on the second-line treatment. This is in the CML-CP patients, patients who use either imatinib or one of the second-generation dasatinib or nilotinib and then immediately after the first line using the Olverembatinib. You can see MMR rate is over 40%. And actually, in the patients who in the first line use the second-generation compound do receive even better response.

Another very exciting efficacy data is in this rare MM patient population with FGFR rearrangement. Currently, there's really no effective treatment. And we take quite a few efforts to enroll about 20 patients. And as you can see, they have a really robust activity, including the CMR rate and also a complete response after the transplant.

Another really deep remission is in the blast phase CML patients. I think in the interest of time, I will not go into detail, but I think it is important to note is that the Olverembatinib has really broad and strong activity against almost all forms of the CML. The important data is on the safety. I think over the last couple of years, including actually, I forgot to mention, we entered the partnership under the option agreement with Takeda in about 2024, I think. Takeda is a great partner in CML and ALL globally. I think this is actually a 4-year follow-up of the registration trial we did. One thing I want to mention in China, actually, CD have a very high bar. This patient population, they have to fail all 3 TKI, okay? Majority, almost globally, all the registration trial is after 2 TKI. And this particular study, over 140 patients, majority of them had to fail all 3 TKIs, not just imatinib or dasatinib and also nilotinib in China. Of course, this is looking for the EFS as a great data. And the 4-year follow-up, as you can see, this is the safety profile.

In the hematological AE, this is all grade 3 and above. Actually, over the time, because of the benefit of treatment to clear the cancer cells in bone marrow, those with thrombocytopenia, neutropenia actually reduced. The nonhematologic event are mostly grade 1 or 2. I think this is a great safety with a 4-year follow-up.

Another exciting, I think, notable data is actually combination of Olverembatinib with Bcl-2 in Ph+ ALL. In this case, they use the Venetoclax because that's already approved on the market. Remarkable efficacy in the chemo-free setting. And more importantly, the longest patient follow-up in this particular treatment is over 800 days, okay? Of course, we will continue with the PI, the combination of Olverembatinib with Lisaftoclax now.

These are more details of our APG-2575, Lisaftoclax. Lisaftoclax standing for life-saving [indiscernible] class and briefly always just called Lisa, okay? So as you can see, we have the first pivotal Phase II study with monotherapy in -- in the BTK failed patient population approved in China just about 6 months ago. And we are running 4 global studies, especially GLORA and GLORA-4, all cleared by EMA and FDA and major regulatory agency around the world, including Japan.

I want to bring your attention to that the Bcl-2 selective inhibitor actually have really broad multiple heme malignancies. This is just list of 3 here, the CLL, AML and also the MDS. I think the MDS right now, globally no targeted drug approved by FDA in the last 20 years and it's really truly unmet medical need globally and untapped market.

So our solution to those issues is that Lisaftoclax demonstrate great efficacy, entered the statistical guideline, the first time in China and also granted 5 ODD by FDA, okay? I think the notable efficacy data, I will present more details. But more importantly, I think, differentiate the first Bcl-2 inhibitor on the market in the last 9 years, Venetoclax is really the safety profile, okay? I think in all the clinical trials, over 600, 700 CLL patients and overall near 2,000 patients, we really demonstrate this safety profile over the current or only one on the market in U.S., Venetoclax. We designed from day 1, the patient-friendly daily dosing schedule, okay? And we received approval. Overall have a very low tumor lysis syndrome, some studies with 0. And then more importantly, there's no drug-drug interaction observed.

This is really different than the Venetoclax even have a DDI with ibrutinib. Actually, if you know, they recently just released public data, [indiscernible] even have higher risk DDI over Venetoclax. So I think this is highly convenient for patients and caregivers. I think one of the very exciting important study is this GLORA-4 global trial in the first-line high-risk MDS cleared by FDA and EMA. We all know that VERONA trial had a negative result about -- since reported last July. And of course, that's really unfortunate for patients globally. And we are very fortunate to have Dr. Garcia Manero, the leading PI from MD Anderson and also Dr. Xiaojun Huang to lead this global study. I think you will see the data actually really different than the VERONA trial in terms of Venetoclax versus the combo with AZA.

We demonstrated the data in the U.S. study actually that Lisaftoclax has strong clinical activity in AML, MDS as well as those patients who failed Venetoclax, okay? Especially in the MDS, CML, CMML patients, they -- ORR can be 80%, majority actually is a CR. In the exposed AML/MDS patients, we can also achieve about 31% ORR, okay? I think this really demonstrates truly differentiation and strong activity in AML and high-risk MDS patients. These are all U.S. and Australia studies.

This is the summary of our label in China for the CLL, okay? As you can see, we are the first one, the only one with this daily dose ramp-up design, okay? We have only 3 dose strengths, okay, 5 days combination to the target dose and maintain, okay? I think this is the unique strength and also really convenient for patients with CLL. With a single agent after BTK in CLL, actually, this is the first indication approved globally.

I want to also share with you some of the data. Actually, in this patient population, we did a pivotal Phase II. Again, CD has a high bar. They gave us this pivotal Phase II trial design 4 years ago, but a really high bar. They want -- every single patient at that time had to fail the BTK, okay? At that time, BTK was not very commonly used in terms of first line, right? It took us a while to recruit these 77 patients. But also, you can see the data, these patients are really sick patients, right, in terms of [ TP53 ] mutation, 17p deletion and chromosome -- complex chromosome. And then we demonstrate that we can achieve over 62% ORR and also really meaningful MRD negativity and the PFS as well.

So -- and then they -- currently, they still observed in the PFS and OS. The data also had an oral presentation at ASH last month. The safety is also really good with those patients. But in the interest of time, I will not go through the details already presented at ASH. But more importantly, moving forward, I think, Bcl-2 is really -- can serve as a backbone across major -- many B-cell malignancies. This is also an example, we can do the combination with our own small molecule drug, such as with Olverembatinib or our MDM2-p53 inhibitors, either in AML or DLBCL, okay?

I want to point it out that majority of Bcl-2 inhibitor resistance actually is due to the Mcl overexpression, not due to the mutation, right? So any drug can combine, indirectly reduce -- inhibit Mcl-1 will have a synergistic effect. And we are the only company that has those small molecule drug globally.

We also have many other interesting novel pipeline. This is our BTK degrader, APG-3288. I want to point it out, actually, we moved this product very quickly from this decision to go to the program and from the PCC to the IND clearance in less than 2 years. And actually from the PCC declaration, the IND-enabling study to the IND clearance in about 8 months. And we also have other program like APG-5918. This is the epigenetic therapeutic program targeting the PRC2 via the EED. There's multiple indications in heme malignancies besides lymphoma, myeloma and also solid tumor in prostate cancer and more also additional indication in anemia.

This is the data we presented at ASH last month, preclinical data demonstrated the combination with IMiD in the multiple myeloma. I think one of the benefit of this epigenetic target is really to correct this deregulation and restore the function of other important compound, including those in the prostate cancer. This is one example of the activity in CKD anemia model. In China, we already finished healthy volunteer SAD, MAD, completed about the 3-dose cohort in patients with thalassemia. China doesn't have much sickle cell anemia patients. So that's where we see initially clinical proof of concept in the anemia patients.

The last one is the APG-2449. This is a triple kinase inhibitor targeting both FAK, ALK and ROS1. For the ALK, ROS1, we actually received clearance for Phase III registration trial in China. But I think more exciting is maybe on the FAK as well.

But in terms of non-small cell lung cancer, this particular triple kinase inhibition may also offer the benefit because FAK overexpression is related to the ALK inhibitor resistance. And the last one is a tough target, but we have continued our effort is the MDM2-p53. There are many companies working on that, and we have been also working on that for the last 10 years, including multiple Phase II studies. And currently, we are looking for the path for the registration trial with some really truly clinical unmet medical need in the ACC or some of the pediatric sarcoma patients.

So the last one is we also work a long time is the dual Bcl-2, xL inhibitor. This takes a while to develop in the clinic. I think the other peer drug, navitoclax actually stopped all the studies due to some of the target toxicity in the platelets. We solved this problem preclinically by making the prodrug, but still need more study in terms of regulatory path to the NDA. So in the interest of time, I will not go to that much detail.

I think finally, this is a very exciting time to summarize our achievement last year. I think 2025 has been tremendous important year for Ascentage. We achieved the first goal being listed on NASDAQ and also get NDA approval for the Bcl-2 selective inhibitor, Lisaftoclax and also received 2 important clearance from FDA and EMA because these 2 trials are the first-line patients. And for MDS, we are globally the only Phase III studies for the MDS patients, and we are really moving fast on the GLORA-4 enrollment. And POLARIS-1 again, is Ph+ for ALL patients for the first line. And of course, we do everything we can to advance enrollment all these POLARIS and the GLORA registration trial studies.

I think thanks to my team, we work very hard behind the scene. As I'm presenting here, all the major achievements come from our team's effort. Looking forward to the 2026, I think the first and most important one is focus on execution, complete the enrollment for all the registration studies. And also, of course, we will have a continued growth and reach out to more patients in our commercialization effort. And we're looking for the NRDL coverage for Lisaftoclax and advance our BTK protein degrader and also the EED inhibitor in oncology and also anemia, both U.S. and China. I think there's a lot of excitement to come from Ascentage team this year.

And finally, I think I want to enter this slide that from day 1, we focus on the patient, focus on the global market. Right now, actually, you can see there's one missing we have 7, what we call 7 magnificent small molecule drug with 2 already late stage. One day, one of the analysts told me we should refer us as a super late stage. So we have 2 super late-stage global opportunity products. And actually, with the BTK degrader, we're going to target all major 3 lineages of heme malignancies from the CML, ALL, CLL, AML, MDS, multiple myeloma, DLBCL and also anemia.

I think more importantly, we are probably the only company have this chemo-free oral active small molecule drug can do the combination, right? So the combination of our Bcl-2, Olverembatinib, BTK degrader plus other one like EED inhibitor and the MDM2-p53, we are probably the only company who will be able to have this novel single-agent compound and also combination to help the patients globally. Finally, I thank you all for attending, and I'd be happy to answer the questions. Thank you.

Thank you, Dr. Yang. Thank you so much for joining us. Welcome. Let's start the Q&A. For those who are in the audience, if you have any questions, feel free to raise your hand. And for those joining us virtually, you can also submit questions on the portal.

Dr. Yang, first time on the main track at the conference, so welcome. Ascentage had been such a strong performer last year out of the NASDAQ IPO. How do you think about where you stand today from a strategic standpoint? I think part of the observation that we see is that U.S. investors haven't gotten to fully know the story, right? So how do you think about getting traction with investors? How do you think about maintaining your strong position also from a liquidity standpoint as well?

Thank you, Brian. Really good question. Okay. So that's a very important question. First, I think by listing on NASDAQ, we really have the opportunity in the last year to participate in many meetings and the calls, presentations with investors and analysts in U.S. and European countries. But I think more importantly, we will be F-3 eligible next month. We will do everything we can to attract the investors in U.S. and European countries through like ATM, many other approaches. I think that's very important to be able to have more participation, communication, interaction with investors and also have the ways for them to purchase Ascentage stock.

Great. Well, let's start off with something new. I think we've done a lot of work in the past on Olverembatinib and Lisaftoclax. Last week, you announced that there is an IND clearance for a BTK degrader by the FDA. How much can you tell us about the program? Can you talk about just a big picture, how does that fit in, especially now that you have late-stage Olverembatinib and also Lisaftoclax in the pivotal studies?

Great question. I think the BTK degrader first demonstrated our R&D capabilities. We entered -- designed that program and then getting the PTC in less than a year. And from PTC to getting the -- filing the IND about 7, 8 months and received the IND clearance within 30 days through the FDA. And we're looking for -- this is public information that CD already put on the website, starting the clock. Nowadays, CD can be getting IND cleared by 14 days, 14 working days.

I think this is the first time for us to getting the true novel degrader into the clinic. But more importantly, I think with the BTK degrader, first, in terms of clinical program, they will take care of all these inhibitors covalent, non-covalent or mutation or not. That's very important, right? Second, this will allow us to have a combination with our Bcl-2 inhibitors, especially. And also, more importantly, we will demonstrate probably more potential moving forward in the lymphoma. So always using this as the analogy of having Army, the Navy and the Air Force working together to target 3 lineages of heme malignancies, lymphoid, myeloid and lymphoma. And then we have all these 3 orally active targeted small molecule drugs.

That's a Chinese saying. Maybe just go back to the Phase I setup for this BTK degrader. How should we think about this Phase I -- how much can you tell about the dose escalation of the Phase I? And I guess, let's say, down the line a year from where we stand, what should we be focusing on from the first Phase I data cut?

I think the first one -- I mean, Phase I is a typical dose escalation, safety, PK and potentially some efficacy. I think in this case, one benefit for especially our team being able to work both the U.S. and China with the FDA and the CD clearance. This is really truly the first Phase I global protocol, okay? It's one protocol cleared by FDA and the CD, so we can enroll the patients simultaneously. Don't need to repeat, right, the dose part. I think the second, of course, the Phase I typically is all-comers, but we will try to enroll more those potentially benefit with a single agent as well, some of the lymphomas, the CLL. But then we will really move quickly either monotherapy for a certain indication, registration trial or very quickly into the combination with our Bcl-2 inhibitor.

Okay. Maybe just quickly on turning into commercial preparation for the U.S. You have multiple global -- studies are ongoing across Olverembatinib and Lisaftoclax. I mean, I think the commercial question is really leaning on more towards the Lisaftoclax compound, right? So where do you stand in terms of preparation for a commercial launch here? What is currently in place? And how do you think about your 2026 and 2027 as you kind of approach that commercial milestone?

Great question. I think 2026 and 2027 will be a turning point for Ascentage to be the global commercial stage company. I think with the 4 registration trials ongoing, some of them, we're looking for the NDA filing in 2027. The first one, Olverembatinib, our commercialization will be helped by our partner, Takeda. The second one, Lisaftoclax, I was told by many experts in the commercialization says you need to be at least minimum 24 months in advance to be ready, right? So I think we are actually in the effort to looking for the Head of Commercialization, CCO in U.S. And then hopefully, we can bring up the team, be ready for commercialization in U.S. next year. But of course, at the same time, we are open, flexible and willing to sell, to partner.

And just turning to -- any questions from the audience? And just turning to the broader portfolio. You have 7 assets in the clinic, 2 approved products in China. How do you think about prioritizing? I know that there's a lot of excitement around BTK degrader. Is that where you think investors should focus on? I guess this question is more of who is your favorite child? How do you think about prioritizing and where we should do more work on?

Great question. I think, first, we are financially strong. Our budget -- our CFO and the Head of Finance are here. We have sufficient funding to support all the R&D programs through 2027. Of course, we do need to prioritize. We cannot do everything at the same time. But I think the 2 things will be that the -- for registration trial, okay, especially to the first line and relatively quick readout in terms of the primary endpoint, that's where we need to focus. That's why I always tell the team this year is the focus on execution, right, the enrollment, enrollment, enrollment.

Second is to be ready for the NDA filing and commercialization, right? We don't want to be late, right? At the same time, we also want to bring the BTK degrader forward, the EED or PRC2 inhibitor in both anemia and oncology. But at the same time, we are open for all the potential partnership, not just the late-stage program, but also those exciting new targets. As you can see from both the ASH presentation and this conference, there are several peers who are doing quite well with their Phase I data.

Great. Well, thank you so much for your time today. This has been great and congrats on all the progress.

Thank you.

Okay. Nice to see everyone here in the room today. I'm John Whittaker with the Citi Investment Banking team. Excited to have a discussion with Ascentage here this afternoon. And Veet, obviously, you're new to the sea. Congratulations. And I think it would be helpful, certainly introduce yourself. And I think it would be helpful to provide a bit of a background on Ascentage. The company overall. And obviously, you just had your first half update a couple of weeks ago and highlighted some key progress and milestones to be attentive to on the horizon.

So maybe take a couple of minutes to talk about the company and some of your key updates from August.

Yes, sure. Thank you, John. Thank you for having me. Happy to do that. Yes, so I joined Ascentage as a CFO a couple of months ago, beginning of July. Been a couple of months, but it feels like it's been a couple of years' worth of activity. So very -- maybe I can start by talking about the innovative pipeline that we have.

As it relates to the company now, we have 2 differentiated novel oncology products now being sold in China. So our first asset, olverembatinib is a third-generation BCL BCR-able TKI. So this is a very important area where the company got -- initially, it got what's known as conditional approval in China about -- in 2021. So this is very much like accelerated approval in the U.S. And eventually, the company got full approval and importantly, for both patients with or without mutations.

And in fact, the label was quite favorable in that it's applied for patients who are resistant to first or second-generation TKIs and/or intolerant. So this and/or -- the intolerant part is important because these patients, as a result of these TKIs that are first generation, second generation, they have issues like diarrhea, et cetera, and they go on to another TKI. And so in our case, this is kind of considered near second line that would be -- one could even say considered as a 1.5 line.

So very pleased with olverembatinib's progress. It eventually then got on to the NRDL which is, as you know, the mechanism in China for reimbursement, which is very important because initially, patients have to pay like RMB 10,000, RMB 15,000 a month, which is difficult for these families. So to get on NRDL opens up about 70% the population for market access. So that's very important for olverembatinib. And you can see that what's also very interesting about this asset and provide a lot of tailwinds for the company last year, which was one of the reasons why the company generate a momentum for the dual listing in the NASDAQ.

Initially, this company was -- became public on the Hong Kong Exchange in 2019. During the wave of China essentially supporting innovation in general and in 2018, as you know, I won't take you through all the details. I'm sure you know it very well, but kind of exploited the exchange, allowing innovative companies to go public. So 2019 was when we did that. So in the span of essentially 5 years came a dualistic company, stock has generated good momentum, I believe, where the -- fortunately, the top-performing NASDAQ IPO in the last several years, and that's 30-plus companies going public. So, And that's olverembatinib and the deep pipeline in the clinic in China being developed during that time.

So the last 6 months actually have been particularly exciting. We got the second drug approved lisaftoclax, which is select selective Bcl-2 inhibitor. So this is very important because prior to Bcl -- prior to lisaftoclax, venetoclax has been the mainstay, the only approved Bcl-2 inhibitor, and that was 9 years ago by AbbVie, right? So this was a very exciting time for the company. Pretty broad indication set in terms of what lisaftoclax can target as it relates to NHL subtypes. So the approval was in CLL/SLL. And also, we were fortunate on the label in that case as well, where it's directed towards patients who have taken at least 1 systemic therapy, including BTK inhibitors.

So not refractory. It's not an RR population as well, right? So I'll bring back the same kind of consideration. It's like 1.5 or even 1.1. So very pleased with having that profile of approval. And of course, with the lisaftoclax, this is one that we plan on exploiting on our own. We made some heavy investments as it relates to commercialization and because we need to have this first mover advantage tailwinds and take -- exploit that. So we actually doubled our sales force in 3 months leading into that.

And then we have a number, as I mentioned, active programs going on in the pipeline. I think one thing that's exciting is our triple kinase inhibitor, the FAK, ALK/ROS inhibitor. That actually opens up a foray into solid tumors along with 2 others, our MDM2-p53 inhibitor and the BCL-2, BCL-XL inhibitor going after NSCLC, ACC neuroendocrine tumors, ovarian and others.

And then we also have an EED inhibitor as well. So we're going after an epigenetic targets, which targets both 2 key areas of anemia. We have patient data in sickle cell. But we're -- I think for the near term, we're exploiting the oncology lymphoma side. And that's not to mention what's beyond that, which is our protein degrader capability. So we're very excited about that. I'm going to be talking more about that in the months ahead. So please stay tuned.

Well, congrats on the -- all the progress and the breadth of the progress as well. I think we all appreciate just how deep the pipeline is and how productive the R&D engine has been at Ascentage. Obviously, getting the approval this summer, for Lisaftoclax was a big milestone for the company. And to your point on the label being broader, not limited to relapsed/refractory patients. And that opportunity to be used earlier in terms of line of therapy. How should we be thinking about kind of the go-forward milestones for the product? Obviously, we will now be looking at sales at each of your updates, semi-annual, if not more frequently.

So I think the commercial launch and the uptake will be important. As you said, you've made a significant investment to really turbocharge the launch. But there's also some active studies that continue to create opportunities to expand the label. Is that right?

Yes. No, that's exactly right. So a very good question. Yes. So I think we have lots of, I would say, commercial and mature catalysts ahead. So I'll kind of walk you through it. So yes. So as it relates to sales, so let's take olverembatinib. Now it's on the NRDL for all approved indications, right? So there's a price set for that, that's a stable price -- so now I think we can give some good -- the market can get some good visibility on the growth of olverembatinib.

We're very happy with the first half report where we disclosed that we had 93% period-over-period jump in sales. And that's driven by a 47% increase in hospital penetration because, as you know, in China, you got to get to the hospitals first, which is exactly what we're doing with lisaftoclax. So lisaftoclax, we are going to be similarly applying for the NRDL as well going into next year. So hopefully, we'll get the same -- give the same guidance there on timing. So that's the commercial area.

Also, as you know, we got this very strong validation from Takeda as it relates to the option on olverembatinib. So that's ongoing. We have a very close relationship with Takeda, very collaborative as it relates to all the trials we're running globally. We're including in the U.S. And so those are kind of some key commercial late-stage assets or catalysts. And then, of course, as it relates to lisaftoclax, right, the -- a major call it lot, call it, also some foresight about preparing for a major market opportunity, which is MDS, right? So we got the Verona news from AbbVie, where the hazard ratio and overall survival was 0.904, and with GLORA. I think 3 things. It's important. They're GLORA-4 here in the U.S.

So one is that we essentially now have clarity about how to execute GLORA-4 because of the news, growing news, it's a key thing because it was clearly -- it was a bit of an overhang on us, actually. We're kind of waiting for that to come out. And it was kind of rumored at ASCO that Verona would turn out the way it did and then the confirmation came in EHA. And I think that also is what contributed to our series of events that led to some good stock momentum. And we appreciate working with you on the -- taking advantage of that on the follow-on that we did in July. So kudos to the Citi team there, one of our partners.

The second thing is, this is, I think, quite remarkable and perhaps even, dare use this word, which is the protocol. Protocol is identical as it relates to China, Europe, U.S. So this is also something we're very excited about here. So it's a pretty, I think, clear trial design going against Aza. We all know kind of the response rates with Aza, right? The OR kind of be kind of around the 25% range. And our data to date show that we well exceeded that. So that's another important point.

And then, of course, MDS, right? So this is a disease category where there hasn't been a targeted therapy approved in 20 years. So we're -- now that we have very exciting registration trial going on in MDS and also validated kind of the differentiation we have as it relates to venetoclax, not -- that's besides the differentiation as it relates to dosing. But the toxicity profile much more favorable on the lisaftoclax end. Remember, it got approved as a single agent. So that's key here. And venetoclax also didn't make it similarly in multiple myeloma as well, not once but twice. So that's another opportunity.

And to your question about catalysts, stay tuned there because I think we'll have more to say on the multiple myeloma side. Now of course, venetoclax is a good drug, right? It's a drug that's been very effective and potent. And another -- there -- I think they're going to continue to be a very important drug in AML, right? They're essentially a standard of care in AML. But we have very strong data that shows potency and a good safety profile in patients that are refractory to venetoclax in AML. So I think we're going to get some good opportunity there, and it's just going to continue to show the validation.

And then, of course, there's CLL, right, where we have 2 other studies. We have GLORA and GLORA-2. And I think this is very important to spend like a minute on because I think we get the question a lot about how do we differentiate ourselves against our competitors, and it's no secret, like B1 is a name that comes up a lot. And how do you -- what is your strategy there given what all the good work that B1 is doing,. Well with GLORA, GLORA-2 and now with the single agent lisaftoclax proven ability to get approved. We're giving essentially patients potential choice here in terms of managing their CLL, right? We have lisaftoclax alone, and then we have patients that are -- already have a history with the BTK and want to work in lisaftoclax, and that's GLORA and also patients who want to have -- are having fresh start therapy with a BTK inhibitor.

In this case, we're pairing with Acala by AstraZeneca. So this is -- I think this gives us -- these are all multibillion-dollar markets and gives us good -- we're pretty much hitting every important blood cancer, except for DL/BCL. So I think that's something that will provide lots of catalysts going forward.

Well, I will look forward to the update on MM and I think bringing that more into focus. Your commentary on MDS being a very underserved market and a large market opportunity. Is there a defined time line for any updates on that MDS specifically?

Yes. No. Like at this point, we just launched a trial that you bring up a very important point. I think this is going to be an important catalyst for the company in the next few years, the progress there. So I think it's only right that the market is focused on how is the progress going with enrollment. What's the cadence there. So we'll be giving an update on that when appropriate.

Yes. Okay, great. Well, we all look forward to that. And you actually preempted my last question around lisaftoclax around the competitive dynamic. And Sonrotoclax from B1, obviously, coming out as a second generation. Those competitive dynamics, but I'm sure we'll be very much in focus. And your comments around where we might see the different lisaftoclax versus Sonrotoclax get used in these patients. It's obviously a large market. There's room for multiple therapies. Is that something that will -- you'll be speaking about in terms of can we expect to see areas where lisaftoclax will hopefully be the drug of choice perhaps not all of them, but talking about those specific opportunities in patient groups where we can win, so to speak?

Yes. No, we ensure, without a doubt. I think you'll see the narrative play more towards what we've been trying to set the stage for with the development programs that we have right now. That's probably the best way to put it. We wanted to -- the company has -- this company essentially the work here with lisaftoclax goes back to -- if you go back to Bcl-2,this is a target that was first identified, I believe, in 1984, right? And it wasn't until the 2 co-founders, Dr. Wang and Dr. [indiscernible] Wang and our CEO and Chairman, Dajun Yang.

Going back to 1996, 1997, is where they first contemplated going after Bcl-2. So I think this company -- the other thing I think is not too well known about this company is that the company has really focused a lot on the U.S. when people think that first INDs that were filed with the FDA as opposed to the CDE. That was certainly the case with lisaftoclax. So the company has always had its eye on the ball of being global. We're conducting trials in outside of China, in Australia, Europe, India. So now it's more about, I think, as approvals happen, registration studies, readout, the differentiation is shown, physicians and families are more informed about the type of regimens and patient populations where these drugs a single agent or in combination can be exploited. So we're very excited about that because it's very much community disease categories as well as specialty categories as well.

Right. Well, and your question, bringing me nicely to just a question or 2 around olverembatinib around that globalization. And obviously, it's super encouraging to see the uptake and the utilization in China. And obviously, the opportunity to continue to see that grow. But maybe spend a minute just about the relationship with Takeda and what should we be looking for in terms of any updates on the global development?

Yes, absolutely. So a few things there. One is really appreciate the validation that Takeda provided. I mean this is a company that has the third generation -- the other third-generation TKI ponatinib, which they have been very successful in getting to the market to patients. And of course, Novartis has cinemib, but that's a different mechanism of action, that's an allosteric inhibitor. So with Takeda, we didn't disclose obviously the full agreement, but what we disclosed is that when we entered into the -- when Takeda entered into the option agreement with us, that was associated with 100 million upfront, 75 million equity investment. So we appreciated that support, provided good momentum into the NASDAQ dual listing.

And Takeda, between the potential option exercise and milestones, that essentially totals $1.2 billion, what we disclosed and royalty ranging from 12% to 19%. So the relationship, to answer your question, we're operating almost as if we never even entered into the agreement in terms of the resources that we're applying. We're assuming that in full faith and exploiting the potential of olverembatinib, making all the necessary investments. I think in one of the trials that speaks to that in terms of hard evidence is the GIST trial, the GIST trial where this company did a really good job identifying the STH mutant patients and showing particular efficacy, and we're investing in China to run that trial as well.

So yes, very close communication with Takeda, Polaris 2, increasing number of sites, enrolling well, Polaris 1, good discussion with the regulators here with the FDA as it relates to giving more details on that one as well in PH-positive ALL, which is obviously another, I think, catalyst that investors are going to be looking for there. We expect to deliver good news there in terms of rolling that out.

Okay. Good to hear. I mean it sounds like there should be some good data flow coming from the asset. I won't ask you for the specifics on milestones, but presumably, after they are received, you'll be communicating about that.

Yes, yes. It's very important now that we have potentially 3 U.S. registration studies that are going to be essentially -- 2 of them already ongoing. It's going to be very important to give updates as it relates to the progress but we fully intend to do that. It is important to get this financing done. I think it's given us now cash through 2027. So it's given us another year. And we're now very much, not to sound too cliche, but all these things we have ongoing, it's all about execution, right? The trials, commercialization rolling out the protein degrader candidates. So that's all in plan fully funded.

Is it fair to say as we look at the way you're developing just in China and expanding those indications there that we will look to see a similar framework followed for the global development as well?

Exactly like China and also other countries as well like India and Australia. This company has been very good at derisking in multiple ways. We know now, obviously, in the commercial side, which is no small feat. So -- and as you know, we're going up for solid tumors as well with 3 of our disclosed pipeline assets. So we get a lot of information as it relates to patient populations, which actually is applicable in other countries, including the U.S.

And as long as we develop the later-stage trials according to what the regulators want in terms of balance, in terms of population and country representation. These are the lessons that we've learned along the way that will apply going forward.

Right. It makes a lot of sense. And obviously, the significant efficiencies to include Chinese sites and patients in any global registrational trial. And it does seem like the way you've generated the clinical data to date, getting some of the approvals and perhaps in some of the later line, heavily pretreated patients continuing to see opportunity to expand the addressable population as we think about pulling this forward. And then that's true on the lisaftoclax side, too. But...

And also the combo of olverembatinib and lisaftoclax. So as you all well know, this is particularly exciting because we've got 2 drugs that got approved on a single agent basis. And it's important to understand that for younger patients with ALL, PH-positive ALL, we have generated data. Yes, the end is small, but the response rate very high as it relates to complete responses. The combination of the 2 in a particularly young pediatric population, that's meaningful. And it's really what that particular segment wants. So I think that's an important area to point out as well. In addition to also in that same population showing strong efficacy in venetoclax refractory patients.

I know something that we talk about -- you talk about is the ability to spare some of these patients from chemotherapy and just the burdens that come along with that. To date, I believe most of the combination data is in the relapsed/refractory patient group, right? Is it appropriate to think that there could be an opportunity to bring that into a frontline PH-positive ALL setting at some point?

Yes. So it's interesting, like, these patients, I think we have enough data where the combination of lisaftoclax plus low intensity chemotherapy very much suited for a pediatric population. So we can go straight to that. And then as it relates to -- it's kind of a barbell, right? Where there's also the elderly unfit AML population as well.

So as it relates to the combo of Lisa and Bleno. And by the way, these patients also take ponatinib as well. So they go through the ringer no question about it. But fortunately, so far, we have to prove this out in the long run. We may have an effective approach for the elderly unfit as well as it relates to Bleno. And then as I mentioned, the combo with Lisa and olverembatinib as well. So thankfully, we have some interesting menu of alternatives here on the ALL side. We get questions about that a lot because it's very important because given the conversion of ALL to MDS, right?

So yes, so we have a number of active pipeline programs here. So these types of decisions need to be made as it relates to combination approaches.

Well, it's clear with the 2 now approved products, there's a real depth of expertise on the hematology side. Maybe shifting a little bit to the solid tumor side. You mentioned the GIST study. But I think at the outset, you talked a bit about 2449. And maybe we would just spend a minute, I'm not sure we have time to talk about the entire pipeline. But if there are a couple of assets that we should make sure people are focused on where we have the opportunity to do something that is first-in-class, best-in-class. I started with 2449, but feel free to start with another, if you prefer.

Well, absolutely, happy to start there. So 2449, very interesting because more and more, I think, there's increased awareness as it relates to -- so 2449 is our triple kinase inhibitor for the listeners. As it relates to -- so it's a FAK ROS/ALK inhibitor, we're carrying out a study in China as it relates to NSCLC in ALK-resistant patients. So in ALK therapy directed patients. So I think the awareness now is, obviously, the ROS pathway is heavily exploited. Lots of companies to variations on pan-RAS, G12C, G12B, et cetera, no matter what the particular RAS candidate is, I think there's increased view that it should be combined with the FAK inhibitor.

So this is going to be, I think, exciting for us to prove that out because both the RAS and FAK pathways, eventually, they converge into the program cell death downstream pathways. But FAK, particularly upregulates the YAP proto-oncogene, which has a blocking effect program cell death. So in order for RAS to really realize its potential, I need to have a strong RAF partner. And so far, we've shown the data we've amassed a very strong activity even with our FAK inhibitor, even with companies that have FAK inhibitors currently improved. Not to name names, but that's kind of steering the excitement on our end.

Understood. And just to confirm, the registrational studies that are ongoing are currently in China, how do we think about potential globalization of the product over time?

Yes. No, I think we can get there. It's just a matter of, I think, finding the right partner as it relates to candidates. But yes, no, it's our full intention to -- we're happy with the progress. That's why we have a disclosed pipeline here. I think that we'll be talking more about in time.

Okay. Great. Well, clearly, opportunity -- first-in-class opportunity there, right? And it sounds like we're getting increasingly focused on who the most likely patients to respond to ours. So hopefully, we're going to see that play through with higher probabilities of success going forward. Being mindful of time, I had jotted down a question or 2 around 115. But if -- maybe it would be helpful to provide a little bit of background on that asset. If there are other pipeline assets that you want to make sure to highlight by all means, take us to those as well.

Yes. So I mentioned a few things about 115. It's an intriguing approach, right, because -- as it relates to MDM2-p53, it's now kind of been proven out through prior attempts that 1 of the issues is when you knock out MDM you get a feedback loop as it relates to p53 upregulating MDM. So degrader approach actually could actually solve that.

But as far as our current 115 program, we've shown that it's shown strong oral availability. It's been highly selective. And we've gotten 6 orphan drug designations from the FDA just on that compound alone and 2 RP DDs as well, pediatric disease designations. So we're evaluating this actually in multiple tumors, melanomas, T-PLL, or NHL and also liposarcoma, neuroblastoma and also ECC adenoid cystic carcinoma, we're -- that's also a meaningful side of the population -- part of the population set -- targeted set here. Very good disease control rates that we've demonstrated so far kind of in the 80 to 100 range. And particularly with ECC and also shown in combination with PD-1 as well. So still more kind of refinement to do with that asset, but we like the profile of it so far.

Great. It clearly sounds like an exciting opportunity. Another demonstration of the efficiency and the innovative nature of what the R&D team is. Yes, we're very excited to play.

All these targets, right, like MDM, BCL, BCL-XL. I mean, these are I think now over the last -- go back to the 80s to now, these are proven to be very difficult to draw targets. And just a real testament to the co-founders going back to Georgetown, University of Michigan, intellectual property, leading to this. It's a real pleasure to see this saving lives and getting drugs approved.

Yes. I was going to ask one more question, but if there's anything else in the pipeline that you think we should certainly be attentive to and be on the lookout for updates over the next several months or quarters, go ahead and flag them. My last question for you is I know you mentioned about cash runway after the recent financing into '27. Maybe just clarify what your current message is on that as it relates to -- does that include milestones from Takeda? Does it not include milestones? And how we should be thinking about your capital formation strategy going forward?

Yes, absolutely. So I'll get the most important point out on the table right now, which is that it does not assume option exercise by Takeda. So we're independent of that. We got cash through 2027, which is where we want to be, right, to invest in our potentially, like I said, soon to be 3 registrational studies in the U.S., the global trials we got ongoing. We got close to 40 trials ongoing globally. So I'm happy to say that our current cash runway takes into account all of those activities without the any sort of other overhang or anything like that.

So yes, we are really appreciative of the following of investors that we've had over the years. hopefully, they feel like we've delivered. And we did the raise not too long ago and the stock is up meaningfully since that point. We think it's through execution and smart deployment of capital, but at the same time, prioritizing where to spend and taking advantage of an efficient cost structure overall in China, that's all across the supply chain.

And obviously, very strong overall global clinical R&D to translational to discovery all the way to clinical ops team. Here in the U.S., we've hired from big pharma. Just to see all of this come together in a global effort. We -- as a company, we are always, of course, looking to be opportunistic as it relates to raising capital and partnering. And that's -- we have the I think, a world-class team here that's doing that right now.

Great. Well, it's -- I;m mindful, we're up at time. It's really been exciting to see the progress to date. Congrats on the strength and the execution. It's nice to see the stock price showing and recognizing the execution, as you noted, it's a rare bright spot on the biopharma radar to see the IPO performance over the course of the year. So it has been an exciting year. We certainly look forward to an exciting year ahead for Ascentage and thank you very much for the time today.

Thank you, John. Really appreciate it. Appreciate your support.