On Thursday, Ascentage Pharma Group (NASDAQ:AAPG) discussed quarterly financial results during its earnings call. The full transcript is provided below.
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View the webcast at https://ascentage-pharma-1h-2026-earnings.open-exchange.net/registration
Summary
AAPG reported total revenue growth of 29% year-over-year to $44.5 million, with product sales at $41.6 million.
The company is advancing nine global registration trials, focusing on hematology-oncology, with two approved products and several in late-stage development.
Key strategic initiatives include the commercialization of olverembatinib in major pharma markets and the appointment of new leadership for global business development and commercialization.
AAPG's financial strategy reaffirms a cash runway through 2027, despite increased R&D and selling expenses due to strategic investments in global trials.
Management emphasized the competitive differentiation of their products, particularly in terms of safety profiles and combination therapies, and highlighted ongoing efforts in market expansion, including NRDL progress in China.
Full Transcript
OPERATOR
Hello and welcome to the 2026 interim financial results. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question-and-answer session. Also, as a reminder, this conference is being recorded. If you have any objections, please disconnect at this time. With that, I would like to turn the call over to Sumed Neni. You may begin.
Sumet Sun Karaneni, Director of Investor Relations and Corporate Strategy
Thank you, Operator, and good morning, everyone. Thank you for joining today. Welcome to AAPG's 2026 interim results and business update call. I'm Sumet Sun Karaneni, Director of Investor Relations and Corporate Strategy at AAPG. Please note that today's discussion will include forward-looking statements based on our current expectations and assumptions. These statements involve risks and uncertainties, and actual results may differ materially. For a discussion of these risks, please refer to our disclosures.
Joining me today are Dr. Dajun Yang, our chairman and chief executive officer, Dr. Faisal Miara, our chief business officer, Mr. Jim Ziegler, our chief commercial officer, Dr. Yifan Tsai, our chief medical officer, and Dr. Veet Misra, our chief financial officer. Yesterday we issued a press release with our unaudited financial results for the six months ending June 30, 2026. That release and the slide presentation accompanying this call are available in the Investor Relations section of our website.
Turning to our agenda, Dr. Yang will open with a business update, and we will hear briefly from Dr. Miara and Mr. Ziegler on the business development and commercial priorities behind our global hematology franchise. Dr. Yang will then cover our R&D highlights, and Dr. Misra will review the financials. Dr. Tsai will also join us for part of the Q&A session. We will then open the line for your questions. I'd now like to turn the call over to our CEO, Dr. Yang. Dr. Yang, you may begin.
Dajun Yang, Chairman and Chief Executive Officer
Thank you, Sumet. And thank you all for joining us. The first half of 2026 advanced a single objective: building AAPG into a leading global, fully integrated hematology-oncology company. We are a company that discovers, develops, conducts global clinical trials, and is now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide. We are currently advancing nine global registration trials, four of which are cleared by both the FDA and EMA.
Total revenue grew to 44.5 million, up 29% year over year, of which product sales were 41.6 million on a constant exchange rate basis, and we are reaffirming cash runway through the end of 2027. Importantly, and playing a role in achieving our global strategic objectives, we strengthened our leadership with the appointments of Dr. Faisal Miara as chief business officer and Mr. Jim Ziegler as chief commercial officer. Both are with us today. This slide shows we have two approved products and a late-stage pipeline that's highly de-risked.
Olverembatinib, our third-generation BCR-ABL inhibitor, has been approved for CML-CP in China since 2021. Tens of thousands of patients have been treated to date. The longest patients on our drug have been on therapy for nearly 10 years. We now have real-world long-term safety and efficacy data that really few companies at our stage can point to. We also have global registration trials, including FDA- and EMA-cleared studies, that are ongoing. Our plan is to commercialize olverembatinib in the United States and the major pharma markets.
Lisaftoclax, our selective BCL-2 inhibitor, is approved as a single agent in post-BTK CLL/SLL. Globally, we are the second selective BCL-2 inhibitor to reach the market after decades have passed. However, in single-agent post-BTK CLL, we are actually the first to get approved. Lisaftoclax has a unique daily dose ramp-up; we are the only one approved with that label. Enhanced AFib safety, as well as the drug–drug interaction observed to date, is much reduced compared to other BCL-2 inhibitors.
It also has FDA- and EMA-cleared global registration trials, GLORA and GLORA-FO. Behind those two, we also have five additional clinical-stage assets, all conducting trials in the US, China, and the rest of the world: APG-2449 is a triple kinase inhibitor covering FAK, ALK, and ROS1; the MDM2–p53 inhibitor APG-115; and APG-1252 targeting both BCL-2 and BCL-XL; the EED inhibitor APG-5918; and also the newer one joining this year to the US and China phase 1 trial, the APG-3288 BTK degrader.
In light of our mission to build AAPG into a leading global hematology-oncology company, we have strengthened our leadership team in the two areas that determine whether the franchise reaches patients outside China: global business development and commercialization. I'm really pleased to welcome Dr. Faisal Miara as our chief business officer and Mr. Jim Ziegler as our chief commercial officer. Both bring deep experiences directly relevant to the next stage of AAPG growth.
I would like to give each of them a moment to introduce themselves and share what attracted them to AAPG. Faisal, let me turn it over to you.
Faisal Miara, Chief Business Officer
Thank you, Dr. Yang. My name is Faisal Miara. I'm the current global chief business officer at AAPG. I have 20-plus years in oncology business development, search and evaluation, and I was also involved in venture investing across the leading pharmaceutical industry. I was in, as you see in the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, and Ipsen, as well as mid-sized biotech like Kadmon and IO Biotech. I was also instrumental in the deal or the M&A that happened between Kadmon and Sanofi in 2021 for $1.9 billion.
I led multiple global oncology partnering and execution teams at IO Biotech and Ipsen, and when I was at Eli Lilly I advanced ramucirumab as a lead oncology antibody and co-initiated the Pfizer Center for Therapeutic Innovation. So I'm very, very pleased to join this very, very good team at AAPG, and the pipeline is very, very outstanding. And with that, I'll leave it to Jim to give you some information as the chief commercial officer.
Jim Ziegler, Chief Commercial Officer
Thank you, Faisal, and good morning, everyone. I am also very pleased to join the AAPG team. I spent more than 25 years building and leading commercial organizations with broad experience in hematology, oncology, and specialty products across both large-cap and small-cap biopharmaceutical companies. What attracted me to AAPG is the opportunity to take a deep, late-stage hematology-oncology portfolio with two already approved products and help translate this clinical foundation into a global commercial organization.
My immediate focus is on building the foundation for potential commercialization of our products, including commercial strategy, market access, and associated capabilities we will need as our registrational programs advance in the United States and other key markets. I look forward to providing updates on our progress over time. I'll now turn the call back to Dajun.
Dajun Yang, Chairman and Chief Executive Officer
Thank you both. Let's look at the R&D highlights. Our development strategy is the engine for full global commercialization strategy. Two approved hematologic assets anchored, and everything behind them is designed to add to our best-in-class portfolio. Turning first to the BCL2 class, our cornerstone asset, lisaftoclax, was approved in July last year for the treatment of adult patients with CLL/SLL who have previously received at least one systemic therapy including BTK inhibitors.
Actually, we conducted a registration trial for the patients who have failed BTK inhibitors. So for that indication we are actually global first one. But more importantly, we are running four global registration trials, two of them cleared by FDA and EMA. Each of them will have a transformative therapy globally. I think the most important one among the four registration trials for the global strategy is the GLORIA-4 in the frontline high-risk MDS, which evaluates lisaftoclax in combination with azacitidine versus azacitidine alone.
This has been cleared by FDA, EMA, China CDE, and also PMDA in close to 20 countries. Let me also highlight a few key differentiations versus two other currently on-the-market BCL2 inhibitors. As you can see, lisaftoclax was the only one designed with daily dose ramp-up in the beginning and the only one approved with only three dose strands and five-day daily dosing up-plan and then reach the target dose 600 mg and continue. As you can see, venetoclax was first approved about 10 years ago and has a five-week dose ramp-up.
The other one just approved earlier this year with a five-week dosing—I mean the daily/weekly dose ramp-up by the line, those cohorts. Okay, because that program started with 1 milligram initially in the trials; it was nine weeks. I think they combined two into one week. Each week they have to do the ramp-up two times and then total nine dose levels to reach a target dose. I think that's really important for the patients with CLL/SLL—the convenience and also reduced time of hospitalization.
Let's also look at the summary of favorable safety profiles and the better drug combinability. We try to compare in the same setting, same patient population, but also be clear this is not a head-to-head comparison. But if we look at the overall safety profile in terms of infection and the PK variabilities, lisaftoclax is probably the best one among the three. If we look at the AE incidence, lisaftoclax also much lower, and no drug-related death reported to date.
In the PK variability, I think the other two are strong; the only three BCL2 inhibitors, and we show minimal fluctuation in plasma concentration compared to the other two. I think also no dose adjustment required compared to the other two. In terms of DDI issue, I think for the chronic dosing patient, like many hematological malignancies, safety and tolerance and drug interaction risk are important differentiations. Let's also look at the key data in the US trials.
In the MDS, lisaftoclax with azacitidine in frontline produced overall response rate 80% and 50% in relapsed/refractory MDS patients. More importantly, we have 40% CR rate and the time to response also very short. Here we also highlight two representative real-world cases in high-risk MDS since it was launched last year in China. In the first case, a 71-year-old patient achieved a CR after two cycles with rapid hematological recovery. In the second case, a patient with poor response and failed venetoclax then achieved a CRi within just 14 days after switching from venetoclax.
These cases provide encouraging indications of clinical activity, including patients previously exposed to venetoclax. Let's also look at the AML case. The overall CR/CRi rate was 72% with a 61% MRD-negative rate. Response was 100% with patients with NPM1 mutation and 83% in the IDH2 mutation. I think it's important all those trials actually with patients in the US and Australia—this is not the clinical data from China as we previously indicated.
In the case of patients who failed venetoclax, which is truly an unmet medical need globally, we still see a 31.8% overall response rate, with no cases of tumor lysis syndrome—same target, same pathway—and lisaftoclax remains active. I think at least based on the current clinical data, the resistance to BCL2 inhibitor majority are not due to new mutations but MCL1 upregulation and some also with the BCL-XL upregulation. I think that explains partially why the same AML patient failed another class; lisaftoclax can still achieve activity. I think those reflect a key differentiation in the downstream resistance profile and represent meaningful clinical opportunity. But of course, more importantly, with the better safety profile and the lower risk of DDI also provide more opportunity for combination, and in our case combination with olverembatinib would overcome venetoclax resistance in AML. Turning to the second pillar of product strategy, olverembatinib.
I also want to highlight why we believe this can be a best-in-class third-generation BCR-ABL inhibitor to patients with CML in the second line or later settings. This has already been approved and is a highly de-risked asset with several years of clinical and real-world use. In China, we received validation from Takeda, as they hold the exclusive option to license olverembatinib outside Greater China and certain other territories. This was entered with Takeda about two years ago.
Globally, the most important study for CML is the POLARIS-2 Part A, enrolled chronic phase who have received at least two prior TKI, randomized olverembatinib against bosutinib. This is cleared by FDA and EMA. And there's also Part B, which evaluates olverembatinib in patients with T315I mutation. As you know, bosutinib doesn't have activity, so that's the single-arm trial. Overall, you can see this is a difficult second-line patient population which we believe olverembatinib can be most differentiated.
Besides the CML, olverembatinib also has strong activity in Ph-positive ALL, so POLARIS-1 is also important. This is our global phase 3 study in newly diagnosed Ph-positive ALL, again both cleared by FDA, EMA, and CDE, and also with breakthrough therapy designation in China. We have already shown strong Part A data at ASH as an oral presentation last year, and we continue to advance the global study. Let's look at some of the important bridging study led by Dr. Ali Jabbour at MD Anderson. This actually was conducted four or five years ago. Dr. Ali Jabbour, as you know, is a leading investigator in CML and also Ph-positive ALL. In this particular study we enrolled 62 heavily pretreated CML CP patients. More than half had received at least four prior TKIs—they are like fourth or fifth line—and half of them had received ponatinib, and a third of them have T315I mutation. I think with this really poor baseline patient population, we achieved the MMR as a single agent: 42.9% in ponatinib-resistant patients, 33% in asciminib-resistant patients, and more importantly 27% in patients who failed both ponatinib and asciminib. Basically those are the patients without other options, but single-agent olverembatinib had pretty good efficacy. I think this treatment again strengthens the overall differentiation and the clinical efficacy versus ponatinib and asciminib. Also, we have a pretty long-term safety profile. In China the longest patients have been using olverembatinib almost 10 years since October 2016. In this particular patient trial, the longest patient treated in the US is over three years with a manageable safety profile.
Let's turn to slide 16. I want to show some more recent data. I think one case is the second-line trial strategy. Olverembatinib demonstrated 47.6% MMR rate as a single agent. More importantly, the new data just last in this year reported in a prospective controlled data in the second-line/late-line setting, showing a clear benefit from switching to olverembatinib—a type of evidence that remains uncommon in this patient population. I think the differentiation you can see is really dramatic, right?
So if they don't switch to the best-in-class potential olverembatinib, the MMR rate remains only 10%. I think that's a huge benefit in terms of for the patients in the late-line CML. Those patients actually have been treated with at least two TKIs—some of those also with asciminib. Olverembatinib delivered 6-month MMR rate 54%, and then even higher at 57% at 12 months. Those who didn't switch remain only low 20% response. I think, as you can see, this is a huge benefit for patients if they switch to olverembatinib.
Also important safety profile in terms of AEs. Let's turn to slide 17. I think the benchmark is important because the landscape changed over the last two years. I think in addition to at least two years ago the only competitive product we consider is asciminib, but now there are two drugs, 0701 and 11001, in study in the US. But first, I think the most important one, we are the only one to have long-term evidence. The other programs don't yet have it, as those are still in phase 1 or early phase 2.
We have six years follow-up for patients who are in the second line and 10 years for the first line of the phase 1 trial. We are the only one to have controlled comparative data set. Those are new requirements from FDA in terms of Project Optimus—so you have to run the RCT trial in order to get the NDA approved. Another important differentiation in the CML patient population is really the baseline. You can see the patients treated with olverembatinib are more late-line, heavily pretreated, and also with mutations.
I think those data clearly demonstrated olverembatinib as the potential drug of choice in the second line of CML for the patients who failed the most advanced available TKI. And I think I will show you a few more studies in the controlled setting in more details on the next slide. Slide 18 is a real-world analysis of 69 blast crisis CML patients who went on transplant, and 26 were treated with olverembatinib and 43 with the first- and the second-generation TKI.
So the olverembatinib group entered transplant in deeper molecular remission—MMR rate 53.8% versus only 16%, and the CMR rate 23% versus 4.7%. The olverembatinib also had more favorable survival outcome: one-year overall survival of 89% versus 71%, and non-relapse mortality 11% versus 23%. These are the two separate patient cohorts in a retrospective real-world analysis—not a randomized comparison—but again demonstrate important differentiation of olverembatinib in large patient population and how to treat CML patients.
Let's also take a look at the combination strategy in the patients in the POLARIS-1 with a low-intensity chemotherapy in frontline. I think the POLARIS-1 three key important differentiations—the data: one, this is frontline newly diagnosed Ph-positive ALL. In most cases around the world, chemotherapy is still required because of the aggressive nature of the Ph-positive ALL. In the registration trial design we conducted the Part A with the low-intensity chemo.
As you can see, this demonstrated MRD-negative CR rate about 63%. This is almost double the ponatinib in the same patient population—the FALCON trial about 34%. Of course, in the trial data the imatinib only 17%, the dasatinib is only about 20%-plus. So this clearly demonstrates in the registration trial setting olverembatinib is the best among the current treatment options. We also try to enter the chemo-free registration trial. Currently we have data from the oral report at ASCO by Dr. Ali Jabbour at MD Anderson demonstrating that if combined with blinatumomab we can achieve 80% MRD-negative rate and a 91% CRi. We also demonstrate importantly in the pediatric R/R Ph-positive ALL patients—actually those data have been available, reported first time two years ago. We continue to see benefit of safety and overall response. I think very impressively we achieve 89% overall response rate after cycle 2 day 15, and all complete response in an oral chemo-free regimen.
I think this combination data is key because this is two orally active agents, chemo-free, in the pediatric ALL setting. Moving on to APG-115, another asset in our portfolio, small molecule targeting MDM2-p53. It actually holds six FDA orphan and two rare pediatric disease designations. This actually has been conducted in our portfolio for a while, as there's no approved product yet globally targeting the MDM2-p53. As you know, p53 is one of the most important tumor suppressor genes.
But I think you do see some recent progress—that Ipsen acquired Kartos' MDM2 inhibitor, and it was actually pretty decent: $450 million upfront and up to $1.75 billion including milestones for phase 3 program in myelofibrosis. I think that there is probably potential for the MDM2-p53 inhibitor combined with a JAK inhibitor in that trial as an add-on strategy. I think that data is encouraging. We are also currently doing that trial with MF patients.
Again, this remains wholly owned by us. In ASCO we presented encouraging data for APG-115 in combination with lisaftoclax in the pediatric soft tissue sarcoma patients globally—pediatric rhabdomyosarcoma and other soft tissue sarcomas—truly an unmet medical need. In that setting we demonstrated good combination safety and an impressive 23.5% response rate and also 70% disease control rate. I think those are encouraging data in the clinic, demonstrating the already active agent from a synergy.
I think in the interest of time I try to focus on mostly the key data, and here's a slide to show you that the cornerstone asset of BCL2 inhibitor, lisaftoclax, combinability with three other targeted small agents—all are already active. I think we all know, as I mentioned, that the main reason for BCL2 resistance is the upregulation of MCL1. So we have demonstrated olverembatinib actually can indirectly downregulate MCL1. We not only have preclinical data but now have clinical data to demonstrate that combination of olverembatinib with lisaftoclax can show the synergy, more importantly not just the CML or Ph-positive ALL, but the patients with AML or MDS and the Ph-negative ALL, especially for those patients who fail venetoclax in the AML. And we have clinical data to demonstrate that in addition to what we showed before in the Ph-positive ALL. Again, with MDM2-p53 inhibitor APG-115, now we have clinical data to demonstrate the safety and efficacy, especially in those hard-to-treat soft tissue sarcoma patients. We're also moving into the DLBCL, AML, and MF. Part of the MOA for this combination is the synthetic lethality.
Again, we are the only company worldwide to have all three assets wholly owned by AAPG. In the interest of time I don't have much data to show, but I can tell you that our BTK degrader APG-3288 has advanced well in the phase 1 setting in both the US and China across the B-cell malignancies who were previously exposed to BTK inhibitors. I think we can stay tuned for the progress for both oncology and the non-oncology indications with the BTK degrader.
I think that's all the highlight of R&D. And let me turn the call over to our CFO, Dr. Weed Misara, for the review of our financial results. Great, thank you. So I think with the overall early highlight and financial update, as you can see our last slide shows we have seven active products in the clinic with two of them already landed approved in China. But more importantly, with these already active target agents we cover a majority of heme malignancies from CLL to CML, AML, MDS, and also with clinical activities in potentially multiple myeloma and DLBCL. I think moving forward our goal is to focus on the current global registration trials and reach the NDA stage and build a strong commercialization team outside China as well and to become a global player in the heme malignancies globally. I think that's all for the brief update with the key data and the financial results, and thank you all for joining us and also our team. And then I think now we are open for the Q&A. Thank you.
OPERATOR
At this time if you would like to ask a question please click on the Raise Hand button which can be found on the black bar at the bottom of your screen. When it is your turn you will receive a message on your screen from the host allowing you to talk and then you will hear your name called. Please accept, unmute your audio, and ask your question. We will wait one moment to allow the queue to form. Our first question will come from the line of Brian Chang with J.P. Morgan. Please unmute your line and ask your question.
Brian Chang, Analyst at J.P. Morgan
Hey guys, thanks for taking our questions this morning, and Faisal and James, welcome to the team. Just to start off in China, can you talk about how we should think about the NRDL listing for specifically lisaftoclax later this year? Can you talk a little bit about what's the progress that you have been seeing in China and how should we think about the next updates related to the NRDL listing? And then we have a couple follow-ups. Thank you.
Dajun Yang, Chairman and Chief Executive Officer
Thank you Brian. Very good question. So lisaftoclax was approved in China July last year. We are the first domestic BCL2 inhibitor approved in China and also we are the only one, the first one approved, in terms of post BTK R/R CLL patients in the registration trial. That was a tough trial, but we demonstrated good safety, efficacy, and we clearly show the differentiation versus venetoclax in terms of the only approved daily dose regimen with a clear safety profile and lower risk of DDI.
I think if you're looking not just at clinical data but the NRDL reimbursement, less hospitalization, less risk, and also convenience are all important favorable factors for the NRDL consideration. I think currently as an update we have passed the initial review. We are on the final product list for the NRDL expert review. Right now this year the timeline is actually a little bit ahead of previous timelines. Currently there are two groups: NRDL experts/officials and those health economics experts are conducting the meetings/reviews right now.
So we may call up to a meeting with experts later this month or early September. Then with the final, we are very confident we will get NRDL coverage for these indications in China. Probably the only concern we have or worry in working with the experts is the final price. But of course the NRDL already covered for different indication AML in China is probably a benchmark, but I think we are confident we'll have coverage for this indication, which is important.
In China, the NRDL is not just reimbursement but the ticket to enter the hospital. The majority of hospitals in China rely on the NRDL approval to enter the hospital in terms of prescription, in case of CLL or sales. This is a chronic dosing; patients reimbursed by NRDL means they can reduce their out-of-pocket payment by on average two-thirds, 60–70%. In certain regions the NRDL coverage can be up to 90%. That's a huge benefit to the patients in chronic leukemia setting.
Brian Chang, Analyst at J.P. Morgan
Great. Maybe just also turning to your ongoing clinical studies. Curious if you can talk about what's going on with Polaris-1 and GLORA trials specifically. How's enrollment looking, and just any sense of how we should think about the timing of the next data readout and potential pathway to NDA filing? How should we think about the timing of those milestones?
Dajun Yang, Chairman and Chief Executive Officer
So I think for those questions, maybe we have our CMO, Dr. Dai, on the call. Maybe Dr. Dai can give some answer first. Dr. Dai.
Yifan Dai, Chief Medical Officer
Sorry Brian. So regarding—sorry, I tried to address somebody else's question—could you please repeat the question?
Brian Chang, Analyst at J.P. Morgan
No problem. Yeah, I'm just curious how the enrollment is going in the global studies like Polaris-1 and also the GLORA studies for lisaftoclax. How's enrollment going, and do you have a better sense of when we're going to get the final data cut to file for the NDA?
Yifan Dai, Chief Medical Officer
So regarding all those global registration trials, the team works very hard and we try to complete their enrollment as soon as possible. So it's still under the plan. In particular, the GLORA-4 study perhaps is under the radar and everybody pays particular attention to that global registration trial. Regarding GLORA-2 and GLORA-3, Dajun actually already announced yesterday we already completed the enrollment for GLORA-2, waiting for the data to mature.
GLORA-3 is also very close, and the remaining we plan to complete the enrollment either by the end of this year or early next year.
Brian Chang, Analyst at J.P. Morgan
Thank you.
Dajun Yang, Chairman and Chief Executive Officer
Maybe let me add a few points to what Yifan said. So we have said yesterday on the Hong Kong call that we completed the enrollment for the GLORA-2, which is frontline CLL setting combination with ezra settidine and with fixed duration. And of course that one is not with the FDA because the control arm is the chemo-immunotherapy. But that’s also over 400 patient enrollment, demonstrating our capability in clinical operation. And GLORA-3 is the AML combo with AZA versus AZA alone.
We are in the final stage to closing the enrollment. The GLORA-4, obviously in the high-risk MDS, many people are watching closely. I think a few key points also important this year. One is this is the frontline, okay? The frontline patient with high-risk MDS. In the trial design, similar to the varna, that combo is AZA versus AZA alone. And this has been cleared by FDA, EMA, PMDA, and China. And globally, not because varna fell, but also another BCL2 inhibitor’s varenna class is not on the MDS, not on the registration trial.
And globally we are the only phase 3 registration trial for the high-risk MDS. There's no targeted drug approved in the high-risk MDS in the last 20 years. So this remains globally a mathematical need. And enrollment is doing well because experts around the world in MDS are really enthusiastic and all want to help patients with high-risk MDS. So overall, I think to summarize, we anticipate, as we said before, the enrollment for GLORA-4 and Polaris-1 and -2 could complete by late this year or early next year.
And the good problem to have, we're looking for potentially three NDAs to file the second half of next year.
Brian Chang, Analyst at J.P. Morgan
And if I can squeeze one more in just for the BTK degrader 3288. Do you have a sense of what you want to see from the early data cut so that investors can make a good comparison against other BTK degraders? Do you have a benchmark, internal benchmark of efficacy early on? And thanks for taking our questions today.
Dajun Yang, Chairman and Chief Executive Officer
Yeah, I think all know that the BTK as a target is really competitive, very crowded, and there's many inhibitors—covalent, non-covalent—on the market, and some are doing really well. But the BTK degrader does have advantage at least with some of the current up to even phase 3 data. So we conducted carefully preclinical data to show our drug 3288 versus the other two from Neurex or B1 that have better selectivity and stronger efficacy. But that's again in the preclinical setting.
Currently I think in the phase 1 we are moving along very well in terms of dose escalation for safety. But more importantly, first those BTK-exposed patients, doesn't matter covalent or non-covalent, we want to show some response in those patient populations first. That's important. That's the key differentiation for the degrader. Second, we probably will take some patient populations—the indications that currently BTK inhibitor is not really active.
More so, importantly combination with our BCL2 inhibitor. I think one example in that setting may be the DLBCL because so far the BTK inhibitor hasn't shown good activity as a single agent in that DLBCL setting. Of course there are also a lot of data combined with the BCL2 may have better readout in this patient population. Another potential one, but we don't have data to share yet, is in the lung oncology indication. I think there are many autoimmune indications that could benefit with the BTK degrader.
Brian Chang, Analyst at J.P. Morgan
Thank you Dajun and congrats on the progress.
Dajun Yang, Chairman and Chief Executive Officer
Thank you.
OPERATOR
Your next question will come from the line of Byron Amin with Piper Sandler. Please unmute your line and ask your question.
Byron Amin, Analyst at Piper Sandler
Yeah. Hi team. Thanks for taking my questions. Maybe if I could just start with the Polaris-1 and Polaris-2 trials. Can you just provide us with an update in terms of when we can expect data from both studies?
Dajun Yang, Chairman and Chief Executive Officer
Again for that question, Yifan—our CMO—can address first.
Yifan Dai, Chief Medical Officer
Oh, we just addressed the same question. Let me repeat it. So currently we are very actively enrolling patients and plan to complete the enrollment either by the end of this year or early next year. Plan to submit the NDA next year?
Dajun Yang, Chairman and Chief Executive Officer
Yeah, I think they just add a little bit for the Polaris 2. The filing NDA is 6 months MMR rate after the last patient in. So of course we already demonstrated very strong data in the MR4 for this patient population and we're confident on that. But the key, of course, is finishing enrollment. And for the Prologio 1, the filing of NDA with FDA is the 3 months MRD-negative CR rate. So I think, again, the target enrollment is on track. And with these six-month or three-month endpoints for the NDA filing, we're looking for potential filing of those NDAs in the second half of next year.
Byron Amin, Analyst at Piper Sandler
Great. And maybe just follow up on a couple of questions for oberambatinib. When could we expect to see Takeda make a decision on its option on the license? That's the first question on the global license. And then second, as it relates to China specifically, where are you as it relates to achieving access to 2,000 hospitals in China? I think that was a target that was previously set by the company. And then maybe a question on the BTK with APG3288 — could we see first data at ASH this year?
And are you planning to evaluate also in the MS setting?
Dajun Yang, Chairman and Chief Executive Officer
Maybe answer your last question first. So the 3288 is still ongoing in the phase one trial in the U.S. and China. I think because this is dose escalation and the cutoff for the ASH already ended, we don't anticipate presenting phase one data this year at ASH. But the progress is doing well. Perhaps we can have some to share maybe at EHA next year. In terms of timing for the phase one data, again, we are conducting several autoimmune indications that demonstrated good preclinical activities.
Because of the non-oncology trials in the phase one healthy volunteer, you do need placebo control. That's where we are working to get INDs filed for the non-oncology indications, including MS. But that data will come a little bit behind because of making the placebo control. But we do anticipate the IND to be filed soon with the autoimmune indications. For your first question, I think the Takeda deal, as you know, we entered the global exclusive partnership option agreement two years ago, 2024, and that is again exclusive global outside China and some territories.
And for that, Takeda back two years ago paid $100 million upfront and $75 million equity investment. And there's also a total up to $1.2 billion aggregate when they exercise the option and certain milestone payments, and also the tiered royalty rate from 12% to start up to 19%. I think globally Takeda is a key player in CML, you know, after Novartis obviously. But I think we do believe Takeda is an important global partner for commercialization of oberambatinib.
And one of the main reasons for the option agreement is obviously they have a competitive product, ponatinib, and the potential antitrust issue. But ponatinib patent will expire early next year. I think that's the key component in the option access. And also we do work closely since the option agreement signed with the Takeda team. So we are actually working closely together to advance all the enrollment and a lot of KOL reaches and planning for the commercialization with Gene on board.
We do look forward to working together ahead of the launch with the Takeda team for the great potential of oberambatinib in the global market. I think you have one more question about the hospital, right? I think currently we are doing well in terms of getting the hospital coverage. I think we do, I mean, still have a second half time to report, but we are on track. Currently bringing the total commercial team to about 300, and the goal is to build close to 400 commercial force in China.
I think it's not just the number, you know, 400 staff in the commercial team, but more importantly to cover 80% of market potential with the product portfolio in China. I think that's where the 2,000 hospitals number we try to achieve. We are on track to achieve that with expanding the commercial team and also the leadership both in the U.S. and China.
Byron Amin, Analyst at Piper Sandler
Great, thank you.
Dajun Yang, Chairman and Chief Executive Officer
Thank you.
OPERATOR
Your next question will come from the line of Jeet Mukherjee with U.S. Bancorp. Go ahead with your question.
Jeet Mukherjee, Analyst at U.S. Bancorp
Great. Thank you for taking the question. Maybe just to dig a little bit further into some of these upcoming readouts, just how should we think about setting expectations for Polaris 12 and Glora 4? And then, you know, just turning to oberambatinib, you highlight some of your competitors on slide 17. But if you could just provide some further detail or perspective on what you see are the biggest differences for your molecule versus those competitor agents on both efficacy as well as safety.
Thank you.
Dajun Yang, Chairman and Chief Executive Officer
Really great question. But first, based on the preclinical data, our drug is probably, among all the TKIs or allosteric inhibitors, the most potent one against T315I mutation and also the compound mutations. Because in the BCR-ABL gene the mutation does not just happen in one hotspot. The T315I is considered a gatekeeper mutation differentiating those in terms of third-generation BCR-ABL inhibitor. But on top of that, there's also more than one mutation — called a compound mutation — in the same cell.
Currently, asciminib and also others do not have those strong data. Oberambatinib is the most potent one and also most active one against a wider spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of late-line CML patients. Currently, even though asciminib has an approved label with only the U.S. to treat a patient with the T315I mutation, they need a five-times dose — five-times dose and also in the U.S. that's five times the cost, almost a million dollars. I think that in the late-line CML patients with mutations we do show probably the most potent. Others like TL-118 or tun-701 now with Merck do not have those data. And they are also mostly in the early phase one or two in the U.S. Because of Project Optimus, we had those data four or five years ago with MD Anderson that we have patients basically on compassionate use — patients who failed both ponatinib and asciminib — the patients with no other treatment options.
But because of Project Optimus, FDA does not allow the single-agent, single-arm pivotal phase two trials for the registration. That's why we have to conduct the RCT. We have to have the control arm, like bosutinib. I think none of those competitive products have those data or registration trial agreement with the FDA yet. In the real world, the consensus among the CML experts community is you want to give the best BCR-ABL inhibitor to the patient who failed after first line early.
You don't want to wait after four or five lines; you want to give the strong one, so the CML patient who achieves deeper response like MMR, MRD, CR, or MR4 or DMR or MR4.5. So patients who can achieve a deep response early would be able to achieve TFR and, in certain cases, maybe drug free for many years defined as a clinical cure. I think that's important. That's why we have second-line data. We have the real-world data, prospective comparative study to demonstrate that oberambatinib could be the choice for a patient who failed the frontline — it doesn't matter if it's a TKI or asciminib or any other allosteric inhibitor.
That's the goal. That's the key differentiation we have been showing and presenting with the clinical data.
Jeet Mukherjee, Analyst at U.S. Bancorp
Thank you, appreciate it.
Dajun Yang, Chairman and Chief Executive Officer
Thank you.
OPERATOR
Your next question will come from the line of Gregory Renza with Truist Securities. Please unmute and ask your question.
Gregory Renza, Analyst at Truist Securities
Great. Good morning, and thank you, Dr. Yang, for taking my question, and congrats on the progress. My question just to start is on lisaftoclax — certainly when it comes to the commercial trajectory over this year. Could you just comment about how that's perhaps changed since Sonrow has entered and entered the market? Are these two drugs competing directly, or is lisaftoclax, certainly as approved in the post-BTK monotherapy setting, producing more of a meaningfully different initial patient mix?
And maybe just comment a bit on the five-day ramp-up, as you've mentioned, how that's perhaps translating to more measurable real-world advantages in China. Thank you.
Dajun Yang, Chairman and Chief Executive Officer
Okay, great question. So overall BCL-2 is a very tough target, right? And we have been working on that in the lab for 30 years, clinically for 21 years, advanced three products in the clinic, but only the sofa cost made it to the market. But again, we always compare with venetoclax, and that daily dosing up was a key differentiation in the beginning. We are the only one approved to go to the clinical trial and approve the label with the clinical data.
I think in the CLL patients some of the early risk was in the tumor lysis syndrome. That's why venetoclax and also Surrender class went to this weekly dose or not, and require hospitalization and closer monitoring because of tumor lysis risk. But on the other hand, because venetoclax is already on the market — same with Surrender class — now the differentiation in the chronic dosing patient like CLL is actually the safety, right? If the drug is tolerated well with less tumor lysis syndrome, less bone marrow toxicity; primarily in our case we have a shorter t1/2 that translates into better safety profile — less neutropenia, thrombocytopenia, and also much less infection. Some of the hematologic malignancy patients in the clinic present first actually with infection, like high-risk MDS, and then they find out actually the bone marrow is the one that has the cancer cells. So for the patient with a high risk of infection it is important you have a lower risk of DDI, drug-to-drug interaction, to combine with — not just combined with azacitidine, standard of care for high-risk MDS right now, but also in some cases of marrow disease, especially multiple myeloma, the combination with antifungal drug is essential for those patients. I think the key differentiation, as we alluded to before, is less is more. They compare even with Surrender class now on the market; you see from the label that they even have a higher risk of DDI than venetoclax. I think that the differentiation — in terms of daily dosing, convenience, better safety profile tolerance, and lower risk of DDI — is important for these chronic-dosing leukemia patients.
I think those are the ones we remain confident will show the benefit to the patients globally once it reaches the market.
Gregory Renza, Analyst at Truist Securities
That's really helpful. Thank you, Dr. Yang. And maybe just a question on the pipeline — you spoke highly of APG115 and that development flexibility that you have with the program as well as 3288, and certainly the synergy potential there with your portfolio. Can you just comment about how you and the team are thinking about prioritizing your resources to accelerate the programs beyond the two commercial assets, and which ones you're perhaps most excited about?
Thank you.
Dajun Yang, Chairman and Chief Executive Officer
To be honest, it's hard to say which one is all data driven. Right. But to your question, we are very happy to see we demonstrate clinical benefit in the pediatric soft tissue tumor setting combined with, in our case, BCL2 inhibitor. Right. So one of the challenges for the MDM2 p53 target—that's why currently no approved product yet—is this negative feedback loop and also the requirement of a combination. We have tried multiple, including the combo with Keytruda in the phase two setting, multiple tumor indications, but we haven't really seen the signal for the registration path before.
But currently we do see now, with this combination with the BCL2 inhibitor, the clinical benefit and the MOA of synthetic lethality. On the other hand, even though this is from the competitive product, the Carlos compound also entered the phase three registration trial with the add-on strategy of a JAK inhibitor in MF. Obviously it's encouraging to see Epson enter the acquisition of—with a potentially $1.75 billion. I think there is a potential maybe at the end of the tunnel to see the finally MDM2 p53 inhibitor may enter the market or registration path.
For your question, I think among the pipeline we have five of them right now. Each one of them have unique different strengths, differentiation. Based on the current data, obviously the two new one, the EED inhibitor 591A—we will show the data at ASH this year—we have completed close to 100 patient phase one trial in informal setting. We are very excited to show this data at the upcoming ASH; that's already submitted for the EED inhibitor. There's also potential in prostate cancer in some other settings of a solid tumor.
I think there's a lot of potential in the EED. We are the first one in China, globally the second in oncology setting. I think there are a lot of potential in the EED in both heme and solid tumor. And of course the BDK degrader 3288 is also very exciting in terms of oncology, non-oncology. I think that currently, in addition to the two approved product in China, globally for registration trial, clearly the focus we want to getting the first NDA filed with FDA and those two products.
But as you can see, the five clinical stage assets, at least those three I mentioned, clearly show the leading advantage globally with clearly clinical data. I think those are still early, not reaching the registration trial yet. So I think we have sufficient resources in terms of budget and clinical team to advance those trials. Again, which one is the favorite? It's hard to say. It's all data driven, but I think all these three do have really exciting data and a path to registration.
Faisal Miara, Chief Business Officer
Yeah, maybe just to add to that, you know, as it relates to our presence in China, our legacy in China, we have, you know, we're one of the few companies that can de-risk and gain, you know, real information about how to tactically prioritize our portfolio and what to take and execute, you know, in other countries and globally. So I think that that's important to keep in mind about us.
OPERATOR
Your next question will come from the line of Mayank Mamtani with B. Riley Securities. Please go ahead with your question.
Mayank Mamtani, Analyst at B. Riley Securities
Yes, team, thanks for taking our questions and appreciate the helpful detail. A couple of quick questions on Zaft Plax—I think you were talking about when failure patients development being explored. Could you maybe just touch on how quickly you can generate data there? What does the patient pool look like? And then on glora 4, if you could maybe comment on your expectation for, you know, CR rate and TLS, and how maybe the interim OS analysis would be handled in the study, if there's anything early built in there.
And then I have a follow up question on Polaris.
Dajun Yang, Chairman and Chief Executive Officer
So the first question I think maybe Yifan can answer.
Yifan Dai, Chief Medical Officer
Very great question. Yes. Based on our preclinical data we have reported using the SEPTA class in combination with overemplatinnab able to overcome menuclas resistance, which we have previously reported at the ACR. We also use very preliminary data we submit to this year ASH and, when the data mature, we have data demonstrate the combo able to overcome the class resistance. The data is preliminary but very exciting. We submit the abstract to ASH.
So that's just your question in the process globally, including in China or outside China in US, and we try our best effort try to enroll more renuclass treatment-failed patient population using different strategy based on the known resistant mechanism to target this van resistant AML population either using the combo or our other compound ABG 1252. To address your question, GAARA 4 study as we mentioned because this is a double blind randomized study we cannot analyze the data early because the enrollment is still ongoing.
But as we I mentioned earlier we plan to complete the enrollment either by the end this year or early next year because based on the current design and the dual primary encompasser we were able to submit the NDA and using the CR as the primary endpoint and then continue to mature the OS data sometimes next year.
Mayank Mamtani, Analyst at B. Riley Securities
Thank you, I appreciate the detail. And then on a similar kind of question on Polaris 2, on the treatment effect for 24-week MMR rate, if you could maybe just comment on, you know, what you've powered the study for. And I was also curious because your, you know, MMR rates grow over time, you know, 48, 96 weeks. How are you handling, you know, crossover from control amp and Adenib there—are they, do they have option to get your drug or they're moving on to other trials?
And what sort of longer-term efficacy we can get there?
Yifan Dai, Chief Medical Officer
Very good question. So based on the current study design, at the beginning, actually FDA denied our study design to allow patient crossover from the control arm to the investigation arm. But later on we try again to request the FDA, finally give the green light, allow those patients fail from the control arm across to overemartinib. So that will make the study more attractive, number one. Number two, regarding the endpoints. So currently we use the 24 weeks—at the 24 weeks MMR rate as the primary endpoint.
So the basic study design is the power enough and double the MMR compared to control one.
Dajun Yang, Chairman and Chief Executive Officer
And also just add one—the design of the Polaris 2 in terms of, because of the Project Optimus, right, you have to do the RCT and you have to have a control arm. But in that particular setting, FDA did agree this is a two-to-one ratio and also allow the crossover. Okay. And remember, the Polaris 2 also have the RMB, the mutation with T31 mutation patient only that we can do the single-arm design with 48 patients. Okay. So I think the total Polaris 2 is 333 patients and roll well.
And the six months MMR rate for the initial filing of the NDA was the FDA.
Mayank Mamtani, Analyst at B. Riley Securities
Awesome. Thank you. And last one for Vid, if I may. Just if you could comment, Vid, on your OPEX trajectory and, you know, if you're getting to peak some. So I know you have a lot of registration studies. Just maybe comment on where we are with the R&D spend on what you expect to see with the pipeline over the next 12 months. Thanks for taking a question.
Vid
Yeah, great question, Mayank. So as I said, we reaffirmed our cash runway and we're happy that we've been adhering to our forecasted spending given the scale of our studies globally, multiple countries. And we're at a point now—what we wanted to do for this year was to, you know, de-risk the balance sheet in 2025 so that we can, you know, execute on enrollment. And this year is the year of execution. Enrollment is going well—you know, Dr. Young and Dr. Xia would discuss that—and so I think as it relates to the expenses for the studies, we're now, given we're at the late stages of enrollment, we are now kind of at the peak as it relates to OPEX spend. So all that is going as planned and expected. And we are not only in a position to complete enrollment, but also with the cash we have on hand, but also for the data as well as our multiple NDA filings. So those are the key expected milestones we have with the cash in our balance sheet.
Mayank Mamtani, Analyst at B. Riley Securities
Got it. Thank you.
Vid
Of course,
OPERATOR
Your final question will come from the line of Michael King with Rodman and Renshaw LLC. Please unmute and ask your question.
Michael King, Analyst at Rodman & Renshaw LLC
Thanks for taking the question. Congrats on the progress, guys. Maybe I wanted to drill down a little bit further on the balance sheet question. You know, if you could talk a bit about a little further about capital allocation because you guys do have a fairly hefty burn rate, and even with the Takeda opt in, you know, it's still—you're going to require a lot of capital. In highly competitive markets, even with differentiated products, you do have entrenched competition.
So I'm just wondering how, if you feel entrenched, any urgency to do additional partnerships or other types of arrangements where you could lay off some of the capital allocation demands.
Vid
Yeah, maybe I can start or— Go ahead, Dr. Young.
Dajun Yang, Chairman and Chief Executive Officer
No, no, you go ahead.
Vid
Yeah. In terms of, you know, allocation of our total budget to programs, we haven't given that level of attribution. But as I stated, we have prioritized so that we can align our spend with expected major milestones and catalysts. So obviously that's what we wanted to establish. What we have done is, you know, with the dual listing steps we've taken is allow ourselves, we believe, within as reasonable as possible, maximal flexibility and optionality in terms of various alternatives to raising capital.
Obviously when it comes to commercialization that requires expansion capital, and we believe as a company we've allowed ourselves to hopefully deliver on catalysts, gain value and thereby have less dilutive sources for raising capital going forward. And of course with FASL on board, the optionality as it relates to potential partnerships, when it makes sense as well. So we are not in a pressure for one particular path which is exactly where we want to be at this point.
Dajun Yang, Chairman and Chief Executive Officer
Yeah, I think I fully agree. Just add one more point that our current cash runway, as we stated before consistently, can support our R&D plan through the end of 2027. More importantly, with non-registration trial and for global cleared by FDA and EMA, majority of these enrollment are already done. That's why you see the first six months we have earned expense more than 30% increase primarily due to this heavy enrollment. But the good news is that most part of the cost is already at least more than halfway done.
Of course we remain open, flexible for many options for the fundraising and also partnership, other source of income on top of our positive, continued growth revenue with two products sales in China. I think we're really unique. It's not just because we have legacy and resources in China, but also steady growing revenue income from China and looking forward to for the global commercialization and the revenue as well. Thanks for taking the questions.
Thank you, Mike.
OPERATOR
That concludes the question and answer portion of today's call. I will now hand the call back to management for closing remarks.
Dajun Yang, Chairman and Chief Executive Officer
Thank you all for joining us. I think this interim report again position us well to be the global player in the heme malignancies. More importantly, we are advanced well in terms of all the key registration trials and then with a target to complete them by the end of the year or early next year. But more importantly we are in the position—if you look at some of the competitor or the really excellent biotech company—this time last year I told my team and many investors, AAPG will be a different company by the time next year.
We're looking forward to your support and looking forward to working with our team, investors and HCP globally to make those novel, safe, efficacious drugs into the global market to help patients with unmet medical need globally. And thank you all for your attention and support.
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