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.
Thank you, Operator, and good morning, everyone. Thank you for joining today. Welcome to Ascentage Farmers' 2026 Interim Results and Business Update Call. I'm Sumed Sunkarineni, Director of Investor Relations and Corporate Strategy at Ascentage. 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 discussion of these risks, please refer to our disclosures. Joining me today are Dr. Dejun Yank, our Chairman and Chief Executive Officer, Dr. Faisal Miara, our Chief Business Officer, Mr. Jim Ziegler, our Chief Commercial Officer, Dr. Yifan Zai, 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. Le Jun Yang. Dr. Yang, you may begin.
Thank you, Schmidt, and thank you all for joining us. The first half of 2026 advanced a single objective, building a center into a leading global fully integrated hematology oncology company. We are a company that discovers, develops, conducts global clinical trials and now taking steps to commercialize best-in-class potential therapies for hematological malignancies worldwide. We are currently advancing nine global registrational trials, four of which are cleared by both the FDA and EMA. The total revenue grew to $44.5 million, up 29% year-over-year, of which will product sales of $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 to achieving our global strategic objectives, we strengthen our leadership with the appointments of Dr. Faisal as Chief Business Officer and Mr. Jim Zegler as the Chief Commercial Officer. Both are with us today. I will be sharing preliminary thoughts. So let's look at the next slide. So this slide, we have two approved products and the late-stage pipeline that's a highly de-risk. Over in Botrinib, our third-generation BCI-Ball inhibitor have been approved CML-CP in China since 2021. Tens of thousands of patients have been treated today. The longest patients on our drug have been near almost 10 years now. We have real-world long-term safety and efficacy data that really few companies on our stage can point to. We also have global registration trials, including FDA and EMA-CLEAR, that's ongoing. Our plan is to commercialize oil and bartender in the United States and the major farmer markets. This overclass, our selective BCL-2 inhibitor, is approved as a single agent in post-BDK-CL SL. Globally, we are the second selective BCL-2 inhibitor to reach to the market after decades have passed. However, in the single agent post-BDK-CRL, we are actually the first to get approved to the market. These sulfacasts have a unique daily dose run up. We are the only one approved with that label. Enhanced effort safety and as well as drug-drug interaction observed today is much reduced compared to other BCH2 inhibitors. It also has FDA and EMA cleared global registration trials, GLORA and GLORA4. Behind those two, we also have five additional clinical stage assets over conducting trials in U.S. and China and the rest of the world. APG2449 is a triple kinase inhibitor covering FAK-AUK-ROS1, and the MDN2-PP3 inhibitor APG-115, and also targeting both VCL2 and XL APG-1252, and the EED inhibitor 591A, and also the newer one joining this year to the U.S. and China phase 1 trial is the APG3288 VTK degrader. In light of our mission to build a sandwich into a leading global hematology oncology company, we have strengthened our leadership team in the two areas that determine whether franchise reaches patients outside China, global business development and commercialization. I'm really pleased to welcome Dr. Faisal Miraya as our Chief Business Officer and Mr. Jin Zagner as our Chief Commercial Officer. Both bring deep experiences directly relevant to the next stage of Ascentage's growth. I would like to give each of them a moment to introduce themselves and share what attracted them to Ascentage. Faisal, let me turn it over to you.
Thank you, Dr. Yang. My name is Faisal Miara. I'm the current Global Chief Business Officer at Ascentage. I have 20 years plus in oncology business development, search and evaluation, and also was involved in venture investing across leading pharmaceutical industry. I was in, as you see in the bottom, multiple large pharmas like Lilly, Pfizer, Sanofi, Ipsen, as well as mid-sized biotech like Cadman and IO Biotech. I was also instrumental in the deal or the M&A that happened between Cadman and Sanofi in 2021 for $1.9 billion. I led multiple global oncology partnering and executed teams at IO Biotech and Ipsen. And when I was at Eli Lilly, I advanced Erbitalk and SRAMSA as a lead oncology product or antibodies and co-initiated the Pfizer Center of Therapeutic Innovation. So I'm very, very pleased to join this very, very good team and Ascentage. And then we'll talk about our pipeline. It's very, very outstanding. And with that, I'll leave it to Jim to give you some information on the chief commercial officer.
Thank you, Faso, and good morning, everyone. I'm also very pleased to join the Ascentage team. I've 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 Ascentage 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 Dajin. Thank you, Boz.
Let's look at the R&D highlights. Our development strategy is the engine for full global commercialization strategy. Two approved hematology assets anchor it, and everything behind them is designed to add to our best-in-class portfolio. Trending first to the Reserva class, our cornerstone asset. This our class was approved in July last year for the treatment of adult patients with CLLSL who have previously received at least one systematotherapy, including BTK inhibitors. Actually, we conduct the 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 IMA. 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 GLOR-4. in the frontline high-risk MDS, evaluates lisophil class in combination with azacitidine versus azacitidine alone. This has been cleared by FDA, YMA, China CDE, and also PMDA in close to 20 countries. Let me also highlight a few key differentiations with two other currently on market BCL2 inhibitors. As you can see the result class was the only one designed with daily dose and up in the beginning and the only one approved with only three dose strength and five daily dose ran up plan, and then reach the target dose 600 milligrams and continue. As you can see, the venetoclast was first approved about 10 years ago, has a five-week dose ran up. The other one just approved Sorrento-class early this year, with a five-week dosing, I mean, the weekly dose run up by the nine dose cohorts, okay? Because CERNA class starts with one milligram. Initially in the trials, it was nine weeks. I think they combined two into one week. So each week they have to do the run up two times and then total nine dose levels to reach a target dose. I think that's very important for the patients with CIL, SL, the convenience, and also reduce the 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, the safety profile in terms of infection and the PK variabilities, the server cost is probably the best one among the three. If we look at the SAE instance, the server cost is also much lower. And no drug-related deaths reported today. And in the TK variability, I think the other two are strong, the only three or four inhibitors, and we show minimum fluctuation in plasma concentration compared to the other two. I think also those adjustments required compared to the other two in terms of DDI issue. I think for the chronic dosing patients, like many hematologic malignancies, safety and tolerance and drug interaction risk are important differentiation. Let's also look at the key data in the U.S. trials. In the MDS, the silver class with azacitidine in front line produced overall response rate 80% and 50% in relapse RR MDS patient. And more importantly, we have a 40% CR rate. And the time to response also really 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 CR after two cycles with a rapid hematological recovery. In the second case, a patient with a poor response and failed Vendetta class and then achieved a CRI within just 14 days after switching from Vendetta class. These cases provide encouraging indications of clinical activity, including patients previously exposed to Vendetta class. Let's also look at the AML case. The overall CRCI 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 U.S. and Australia. This is not clinical data from China. As we previously indicated, in the case of patients who failed the mandelocast, which is truly a mathematical lead globally, we still see a 31.8% overall response rate with no cases of tumor lysis syndrome. Same target, same pathway, and the lisovacast remains active. I think at least, you know, based on the current clinical data of the resistance to BCR-2 inhibitor, majority are not due to new mutations, but MCR-1 upregulation and some also with BCR-XL upregulation. So I think that explains partially why the same, you know, AML patient failed in another class, this other class can still achieve activity. So I think that those reflect 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 Orenbutinib would overcome venetocase resistance in AML. Turning to the second pillar of product strategy, Orenbutinib, I also want to highlight why we believe this can be a best-in-class third-generation BCI-bole inhibitor to patients with CML in the second line or late settings. This has already been approved and highly de-risked asset with several years of clinical and real-world use in China. We received validation from Takeda as the whole exclusive option to license or martinib outside Great China and certain other territories. This was entered with Takeda about two years ago. Globally, the most important study for the CML is Polaris II. Part A, enrolled chronic phase, who has received at least two prior TKI, randomized Ombartinib against Bosutinib. This is clear by FDA and EMA. And there's also Part B, which evaluates Ombartinib in patients with T315I mutation. As you know, basutinib 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 ovomalitinib can be most differentiated. Besides the CML, ovomalitinib also have strong activity in pH-positive AL. So Polaris 1 is also important. This is our global phase 3 study in newly diagnosed pH-positive AL. 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 breeding studies led by Dr. Ali Jabu at MD Anderson. This actually was conducted four or five years ago, and Dr. Ali Jabu, as you know, is a leading investigator in CML and also PSA positive AL. In this particular study, we enrolled 62 heavily pretreated CML-CP patients. More than half have achieved at least, have received at least a full prior TKI. They are like fourth or fifth line, and half of them have received the penogenin. And a third of them have TCE15 mutation. I think with this really, you know, poor baseline patient population, We achieved the MMR as a single agent, 42.9% in pronotinib-resistant patients, 33% in asinimib-resistant patients, and more importantly, 27% in patients who felt both pronotinib and asinimib. Basically, those are the patients with no other options, but single agent or botanib have pretty good efficacy. I think this treatment, again, strength, you know, the overall differentiation and the clinical efficacy versus ponotanib and sinemib. And also, we have a pretty long-term safety profile. In China, the longest patients have been using almost 10 years since October 2016. And in this particular patient trial, the longest patient treated in the U.S. 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. OVAR-TNIP demonstrated 47.6 mmR rate as a single agent. More importantly, the new data just last in this year reported. In a prospective control data in the second-line, a late-line setting, showing a clear benefit from switching to ovarimbartinib, a type of evidence that remains uncommon in this patient population. I think the differentiation you can see is very dramatic, right? So if they don't switch to the best-in-class potential ovarimbartinib, 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, you know, have been treated with at least two TKI. Some of those also with acinib. Our body did have delivered six months MMR rate, 54%, and then even higher at 57% in 12 months. Those who didn't switch remain only low 20% response. I think, you know, as you can see, this is a huge benefit for patients if they switch to the ovumviratinev. And also an important safety profile in terms of AEs. Let's also turn to slide 17. I think the benchmark is important because the name market changed over the last two years. I think in addition to at least two years ago, the only competitive product we considered is the Asinamib. But now there is two drug turns, 701 and 11001, in the study in the U.S. Okay. But first, I think the most important one, we are the only one have long-term evidence that other program doesn't yet have, as those are still in the phase one or early phase two. And we have, you know, six years of follow-up for patients who are in the second line and 10 years for the first line of the phase one trial. And we also have, we are the only one have controlled the comparative data set. Okay, those are new requirements from FDA in terms of a project optimus. So you have to run the RCD trial in order to, you know, getting the NDA approved. Another important differentiation in the CML patient population is really the baseline, right? So you can see the patient treated with O-martinib, a more lay line, you know, heavily pretreated, and also with mutations. I think that those data clearly demonstrated O-martinib as the potential, the drug of a choice in the second line of CML of the patient who felt the most advanced available TKI. And I think I will show you a few more studies in the control in more details on the next Slide 18 is a real-world analysis of a 69 blast crisis CML patient who went on transplant and 26 was treated with the O-Martinib and 43 was the first and the second generation TKI. So, the over-empotentable group entered transplant in deeper molecular remission, MMR rate 53.8% versus only 16%, and CMR rate 23 versus 4.7%. The over-empotentable also had more favorable survival outcome, one-year-old survival of 89% versus 71%, and the no-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 overmarchinib in large patient population and how to treat CML patients. Let's also take a look at the combination strategy. In the patient, in the Polaris 1, with low-intensity chemotherapy in frontline, I think the Polaris 1, three key important differentiation, the data. One, this is frontline newly diagnosed, pH-positive L. In most cases around the world, chemotherapy is still required because of the aggressiveness nature of the pH-positive AL. In the registration trial design, we conduct the Part A with the low-intensity chemo. As you can see, this demonstrates MRD-negative CR rate about 63%. This is almost double the ponotinib in the same patient population, the FALCON trial, about 34%. Of course, in the trial data, the imotinib only 17%, the satanib is only about 20 plus percent. So this clearly demonstrates in the registration trial study, oremotinib 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 Javu around MD Anderson demonstrate that if we combine with the brain node, we can achieve 80% MRD negative rate and 91% CR-CRI. We also demonstrate, importantly, in the pediatric RR pH-positive L patients. Actually, those data have been available, reported the first time two years ago. We continue to see benefit of safety and overall response. I think, very impressively, we achieved an 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 agent chemo-free in the pediatric AAL setting. Moving on to the APG1-5, another asset in our portfolio, small molecule targeting MDN2-PV3. It actually holds six FDA ODD 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 MDN2 PV3, as PV3 is one of the most important tumor suppressant gene. But I think you do see some recent progress that Ibsen acquired Cato's MDN2 inhibitor and was actually pretty decent $450 million up front and up to $1.75 billion, including milestones, for phase 3 program in myelofibrosis. I think that there is probably potential for the MDN2-P3 inhibitor combined with the JAK inhibitor in that actual trial as an add-on strategy. I think that data is encouraging. We are also currently doing that trial with MF patients. So, again, this remains wholly owned by us. And in the ASCO, we presented encouraging data for APG1-5 in combination with the several class in the pediatric soft tissue sarcoma patients. Globally, pediatric rhabdomyosarcoma and other soft tissue sarcomas truly amadermetic need. In that setting, we demonstrate good combination safety and an impressive 23.5% response rate and also 70% disease control rate. I think those encouraging data in the clinic demonstrate the already active agent from a percentage. 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 BCO2 inhibitor the server class combinability with three other targeted small agents who are already active. I think that we all know, as I mentioned, that the main reason for BCl2 resistance is the upper regulation of MCL1. So we have demonstrated all bartending actually can indirectly down regular MCL1. We not only have preclinical data, but now have clinical data to demonstrate that combination of the over-artentive with the silver cards can show the synergy. More importantly, not just the CML or pH-positive AL, but the patient with the AML or MDS and the pH-negative AL, especially for those patients who fail the venetocards in the AML and we have clinical data to demonstrate that in addition to what we showed before in the pH-positive AL. And again, with MDN2 PP3 inhibitor APG1-5, now we have clinical data to demonstrate the safety efficacy, especially in those hard-to-treat soft tissue sarcoma patients. And 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 have you know all three assets only owned by a percentage in the interest of time i don't have much you know data to show but i can tell you that our Our BDK degrader, APG32-ATA, have advanced well in the phase one setting in both the U.S. and China across the B-cell malignancies who previously exposed the BDK inhibitors. I think we can stay tuned for the progress for both the oncology and the non-oncology indications with the BDK degrader. I think that's all the highlight of R&D. And let me turn the call over to our CFO, Dr. Witt Misara, and for the review of our financial results. Great. Thank you, Dr. Yang.
And good morning, everyone. Turning to our financial results, the first half of 2026 was another period of continued commercial growth. investment behind our global development programs. Total revenue was $44.5 million compared to $32.6 million in the first half of 2025, representing an increase of $11.9 million or 29.3% on a constant exchange rate basis. Product sales growth has been our main driver, as indicated by, you know, 41.6 million of product sales compromising our total revenues. During the first half, we continued to expand our commercial reach and invest behind both products while maintaining a disciplined approach to managing operating expenses and supporting our and advancing our global clinical programs. Research and development expenses were $102.8 million compared to $73.8 million in the first half of 2025, representing an increase of $29 million, or 32% on a constant exchange basis. As planned, this was our expenditure, and to execute on our high priority to advance enrollment in multiple global registration trials selling and distribution expenses were 33.4 billion compared with 19.2 million in the first half of 2025 representing an increase of 14.2 million or 64.3 percent increase and this was driven by marketing and commercial investment behind our products. Administration expenses were $17.5 million compared to $13.9 million in the same period last year, primarily due to RSU expense. Turning to our balance sheet, we're pleased to report cash balances were $279.4 million as of June 30, 30, 2026, as well as reaffirming our cash guidance runway through 2027, as we've said before. This funds us through multiple key registrational studies ongoing globally. And to emphasize, we are funding nine registrational programs and are currently taking initial steps to building a commercial organization in the U.S. and remain on target for investments required at the appropriate time to fulfill our global strategic objectives. Thank you. And with that, I'll turn back the call to Dajun for his closing remarks.
Dr. Young. great uh thank you we so i think that they uh with the overall our only highlight and the financial update uh as you can see uh our last slide uh to show we have seven seven uh active products in the clinic with two of them already landed approved uh in china and but more More importantly, with this already active target agent, we cover all majority of HIN malignancies from the CLL, AL to the CML, AML, MDS, and also with clinical activities in potentially multiple myeloma and the DLBCL. I think moving forward, our goal is to focus on the current global registration trials and reach to the NDA stage and build a strong commercialization team outside China as well and to become a global player in the human 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.
Hey, guys. Thanks for taking out 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 at least after class 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 of follow-up.
Thank you. thank you brian a very good question uh so the third class was approved in china july last year uh we are the first domestic bcl2 inhibitor approved uh in china and also we are the only one the first one approved in terms of post bdk rr cil sl patients in the registration trial. That was a tough trial, but we demonstrated good safety efficacy and we clearly show the differentiation versus another class or surrender class in terms of the only approved daily dose and up with a clear safety profile and a lower risk of DDI. I think if you're looking not just at clinical data but the NRDL reimbursement, you know, less hospitalization, less risk, and also convenience, all important favorable factors for the NRDL consideration. I think currently, as 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 a previous timeline as currently they both the there are two groups NRDL experts officials and all those health economics experts are conducting the meetings reviews right now so we may call up to a meeting with the experts later this month or early September. Then with the final, we're really confident we will get NRDL coverage for these indications in China. Probably only the concern we have or worry is working with the expert is the final price. But of course, Benarclast is already covered for different indication AML in China. It's 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 a reimbursement but the ticket to enter the hospital majority of hospitals in China rely on the NRDL approval to enter the hospital in terms of prescription and in case of CIL, SIL This is a chronic dosing patients. Reimbursement by NRDL means they can reduce their out-of-pocket payment by the average two-thirds, 60%, 70%. In certain regions, the NRDL coverage can up to 90%, saying that's a huge benefit to the patients in chronic leukemia setting.
Great. Maybe just also turning into your ongoing clinical studies, I'm curious if you can talk about, you know, what's going on with Polaris 1 and GLORA trials, specifically how is the enrollment looking like? And, you know, 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?
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.
Sorry, Brian. And so regarding growth for study, right? Sorry, I had to address this somebody else's question. So could you take the question?
Yeah, I'm just curious how, you know, how the enrollment is going in the global studies like Polaris 1 and also the GLORA studies for Lecephoclax. You know, how's enrollment going? And do you have a better sense of how, you know, when we're going to get the final data a cut to file for the NDA.
So regarding all those global registration trials, the team worked very hard and tried to complete their enrollment as soon as possible. So it's still under the plan. In particular, the GWAR-4 study perhaps is under the radar, and everybody pay particular attention to that global registration trial. Regarding GWAR-2, GWAR-3, Dr. Naturi already announced yesterday we already completed enrollment for GORR2, waiting for the data material. GORR3 also very close, and the remaining, we plan to complete the enrollment either by the end of this year or the early next year.
Maybe let me add a few points to what Yifan said. So, you know, we have, you know, said yesterday in the Hong Kong call that we complete the enrollment for the Glora 2, which is front line CIL setting combination with azacitidine and with fixed duration. And of course that one is not with the FDA because the control arm is the chemoimmunotherapy, but that's also over you know 400 patient enrollment demonstrate our capability in the clinical operation and glora 3 is the ml combo with azar versus azar long we are in the final stage it's closing the enrollment the glora 4 obviously in the high risk mds many people watching closely i think the few key points also important to share one is this is the frontline okay the frontline patient with high-risk mds in the trial design similar to the verna that combo with azar versus azar lung and this has been cleared by fda ema pmda and china and globally not because verna fell but but also another Bcl2 inhibitor surrender class is not on the MDS, not on the registration trial. And globally, we are the only phase three registration trial for the high-risk MDS. There's no target drug approved in the high-risk MDS in the last 20 years. So this is remain globally a mathematical need. and enrollment is doing well because experts around the world in MDS are really enthusiastic or want to help patients with high-risk MDS. So overall, I think to summarize, we anticipate, as we said before, the enrollment for Glorafor and Polaris 1 and Polaris 2 could complete by late this year or early next year and the good problem to have we're looking for potentially three NDA to file the second half next year.
Great 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 you know 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.
Yeah, I think in order that the BTK as a target is very competitive, very crowd, and there's many inhibitors, covalent, non-covalent on the market, and some are doing very well. But the BTK degrader do have advantage, at least with some of the current, up to even phase 3 data. So we conduct carefully preclinical data to show our drug 3288 versus other two from Neurix or B1 that have more better selectivity and stronger efficacy. But that's again is in the preclinical setting. Currently I think in the phase 1 we're moving along very well in terms of those escalation for safety. But more importantly, first, those are all BDK-exposed patients, okay? Doesn't matter covalent or non-covalent. And we want to show some response in those patient population first, right? That's important. That's the key differentiation for the degrader. Second, we probably will take some patient population, the indications that currently BTK inhibitor is not really active. Some, more so importantly, combination with our BCL2 inhibitor. I think that one example in that setting may be the DLBCL. So, because so far the BTK inhibitor hasn't shown good activity as a single agent in that DLBCL setting. And, of course, there are also a lot of data that combined with BCL2 may have, you know, better readout in this patient population. Another potential one, but we don't have data to share yet, is in the non-oncology indication. I think that there are many autoimmune indications could be a benefit with the BDK degrader.
Great. Thank you, Dajun, and congrats on the progress.
Operator
Thank you. Your next question will come from the line of Byron Amon with Piper Sandler. Please unmute your line and ask your question.
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?
Again, for that question, Yifan, our CMO, can address first.
We just suggest the same question. Let me repeat that. So currently we are very actively enrolled patients and plan to complete the enrollment either by the end of this year or the early next year. Plan to submit the NDA next year.
Yeah, I think that they just add a little bit. For the Polaris II, the filing NDA is a six-month MMR rate after the last patient in. So, of course, we already demonstrate very strong data in the MMR rate for the patient population. And we're confident on that. But the key, of course, is the finishing enrollment. And for the Polaris 1, the filing of NDA with FDA is the three-month MRD negative CR rate. So I think, again, the target enrollment is on track. And with these six months or three months, end point for the NDA filing, We're looking for potential funding of those two NDAs second half next year.
Great. And maybe just follow up on a couple of questions. For over-rumbatinib, 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?
Maybe answer your last question first. So the 3288 is still ongoing in the phase one trial, U.S.-China, I think because this is a dose escalation, and the cutoff for the ASH already ended, so we don't anticipate to present the phase one data this year at ASH. But the progress is doing well. Perhaps we can have some to share, maybe EHA next year in terms of timing for the phase one data. And again, we are conducting several autoimmune indications to demonstrate good preclinical activities. And because of the non-oncology trials in the phase one health volunteer, you do need the placebo control, right? So that's where we are working with to getting the R&D file for the non-oncology indications, including the MS. But that data will come from a little bit behind because of making the placebo control. But we do anticipate the R&D to be filed soon with the autoimmune indications. And for your first question, I think that the Takeda deal, as you know, that 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 up front and $75 million equity investment. And there's also a total up to $1.2 billion aggregate when they access the option and a certain milestone payment. And also the tiered royalty rate from 12% to start up to 19%. I think, you know, globally, Takeda is a key player in the CML and the AL, you know, after Novartis, obviously. but I think we do believe Takeda is an important and global partner for commercialization over and one of the main reasons for the option agreement is obviously to have a competitive product and the potential antitrust issue. But the pattern will expire early next year. I think that's the key component in the option X-axis. And also we do work closely since the option agreement signed with the targeted team. So we are actually working closely together to advance all the enrollment and a lot of KLL reaches and planning for the commercialization. with the gene on board we do looking forward working together ahead of the launch with the target team for the uh great you know potential of uh or bartender in the global market i think you have one more question uh about the hospital right uh i think they uh they currently we are doing well in terms of getting the hospital covered. I think we do, I mean, still have a second half time to report, but we are on the track currently bringing the total commercial team about 300. And the goal is to build close to 400 commercial forces in China. I think it's not just the number, you know, 400 staff in the commercial team, but more importantly is to cover 80 percent of market potential with the product, two product in China. I think that's where the, you know, 2,000 hospitals number we try to achieve. We are on the track to achieve that with the expanding the commercial team and also the leadership both in U.S. and China.
Operator
Thank you. Your next question will come from the line of Jeet Mukherjee with U.S. BankCorp BTIG. Go ahead with your question.
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 1, 2, and Glora 4? And then, you know, just turning to Ulver and Batnib, 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.
Really great question. But first, based on the preclinical data, our drug is probably among all the TKIs or all the static inhibitors, the most potent one against the T315I mutation, and also the compound mutation. Because in the BCI-BOL gene, the mutation not just happens in one hot spot. The T315I is considered a gatekeeper mutation, differentiated those in terms of third-generation BCI-BOL inhibitor. But on top of that, there's also the more than one mutation called a compound mutation in the same cell, okay? And currently, Sinimib and also those Terns or 11 do not have those strong data. So OVMR-Ternib is the most important one and also most active one against a wide spectrum of mutations, including the compound mutations. That hurts about at least up to 40% of late-line CML patients. Currently, even though Sinavib have approved label with the only U.S. to treat the patient with T3R mutation, but they need a five-time dose. Five-time dose, and also in U.S., that's five times the cost, almost a million dollars. I think in the late-line CML patients with mutations, we do show probably the most potent one, okay? And 11 or turns 7.1.1 now with Merck do not have those data. And they are also mostly in the early, you know, phase one or two. And in the U.S., because of Project Optimus, you know, we have those data four or five years ago with MD Anderson that we have, you know, patients basically on mathematical need, right? For a patient who fell both Pernatinib and Sinibib are the patient with no other treatment options. But because of the project optimus, FDA do not allow the single agent, single arm period of phase two trials, you know, for the registration. So that's why we have to conduct the RCT. We have to have the control arm like Bosutinib. I think that none of those, you know, 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-adboinhibitor to a patient who failed after the first line early, right? You don't want to wait after four or five lines. You want to give the strong one. So the CML patient who achieve deeper response, like an MMR, MRD, you know, an active CR, or the MR4 or DMR 4.5. So a patient who can achieve a deeper response early would be able to achieve TFR. And in certain cases, maybe, you know, drug-free for many years, defined as a clinical cure. I think that's important. That's why we have a second-line data. We have the real-world data perspective comparative study to demonstrate the OMR-TNIP could be the choice of a patient who fell at the front line. It doesn't matter if it's a TKI or a cinema or any other, you know, allostatic inhibitor. That's the goal. That's the key differentiation we have been showing, presented with the clinical data.
Thank you. Appreciate it. Thank you.
Operator
Your next question will come from the line of Gregory Renza with Truist Securities. Please unmute and ask your question.
Greg, good morning, and thank you, Asantecine, for taking my question, and congrats on the progress. My question, just to start, is just on the septiclax. Certainly, when it comes to the commercial trajectory over this year, Could you just comment about how that's perhaps changed since Sonro has entered the market? Are these two drugs competing directly, or is Lesepticops certainly, as approved in the post-BTK monotherapy setting, just 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.
Okay, great question. So overall, Bixia 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 silver class made to the market. But again, we always compare with vanilla class, and that daily dose and 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 CRL-SL patients, some of the early risk was in the tumor lysis syndrome. That's why vanilla class and also surrender class went to this weekly doser and up, right? And require hospitalization and close monitoring because of tumor lysis risk. But on the other hand, because Vinocast is already on the market, same with Sorinocast now, the differentiation in the chronic dosing patient like CIL is actually the safety, right? If the drug tolerates well with less tumor lysis syndrome, less bone marrow toxicity, primarily in our case is we have a shorter T-half that translates into better safety profile, less neutropenia, thrombocetopenia, and also much less infection. Some of the hematology malignancies in patients in the clinic presented first is actually the infection, like a high-risk MDS, right? And then they found out actually the bone marrow is the one has the cancer cells. So the patient with a high risk of infection is important. You have a lower risk of a DDI drug to combine with, right? Not just combine with azacitidine, standard care for high-risk MDS right now, but also in some case of marrow disease, especially the motomyeloma, the combination with antifungal drug is essential for those patients. I think the key differentiation, as we alluded to before, is less is more. So they compare, even with the surrender class now on the market, you see from the label that they even have a higher risk of DDI than venator class. So I think that the differentiation in terms of daily dose turn up convenience, better safety profile, and lower risk of DDI. It's 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 they reach it to the market.
That's really helpful. Thank you, Dr. Yang. And maybe just a question on the pipeline, you spoke highly of APG 115 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?
To be honest, it's hard to say which one is all data-driven, right? But to your question, we are really 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 MDN-253 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, you know, including the combo with Keytruda in the phase two setting, multiple tumor indications. But we haven't really seen the signal for the registration pass before. But currently, we do see now with this combination with the BCL-2 inhibitor, clinical benefit, and the MOA of a synthetic lethality. On the other hand, even though it's from the competitive product, the CODOS compound also entered the phase three registration trial with the add-on strategy of a JAK inhibitor in MF. And obviously, it's encouraging to see Ibsen enter the acquisition with potentially $1.75 billion. I think there is a potential maybe at the end of the tunnel to see the finally MDN2 PP3 inhibitor may enter the market or registration pass. For your question, I think among the pipeline, we have five of them right now. Each one of them have a unique different strength differentiation based on the current data. Obviously, the two new ones, the ED inhibitor 5918, 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. And for the EED inhibitor, there's also potential in prostate cancer in some other settings of a solid tumor. I think that there's a lot of potential in the EED. We are the first one in China, globally, the second in oncology setting. And I think there are a lot of potential in the EED in both heme and the solid tremor. And, of course, the BDK degrader 3288 is also very exciting in terms of oncology, non-oncology. I think that they currently, in addition to the two approved products in China globally for registration trial, clearly the focus, right? We want to, you know, 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 a clinical team to advance those trials. Again, which one is a favor? 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.
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.
That's great. Thank you, gentlemen, for all the color and congratulations again.
Operator
Your next question will come from the line of Mayank Mamtani with B. Riley Securities. Please go ahead with your question.
Yes, team. Thanks for taking our questions and appreciate the helpful detail. A couple of quick questions on the Zafclax. I think you were talking about when failure patients development being explored. Could you maybe just touch on, you know, how quickly you can generate data there? What does a, you know, 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.
So the first question, I think maybe Yifan can answer.
Very great question. Yes, based on our preclinical data, we have reported using the subclass in combination with over-unpertinib able to overcome vendor-class resistance, which we have previously reported at the ACR. We also use very preliminary data we submitted to this year OSH, and when the data mature, So we have data demonstrated the combo able to overcome the resistance. The data is preliminary, but very exciting. We submit the abstract to us. So that's just your question. We are in the process globally, including in China or outside China in the U.S., and we try our best effort, try to enroll more venocast treatment-filled 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, EBG-1252. To address your question, GARA IV 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 I mentioned earlier, we plan to complete enrollment either by the end of this year or early next year. Because based on the current design and the dual primary interpreter, we were able to submit the NDA and using the CRA as the primary endpoint and then continue to mature the OS data and sometimes next year.
Thank you. I appreciate the detail. And then on a similar kind of question on Polaris 2, you know, 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, crossover from control arm, panatinib there? Do they have option to get your drug or are they moving on to other trials and what sort of longer term efficacy we can get there?
Very good question. So based on the current study design, at the beginning, actually FDA denied our study design to allow patients to cross over 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 to fail from the control arm and cross over to over-emotinib. 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, the MMR rate as the primary endpoint.
So the basic study design is the power enough and double the MMR rate compared to control R. Okay. and also just i don't want the the design of the polarity 2 uh 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 if they you know did agree this is a two to one ratio so and also allow the crossover okay And remember, the Polaris II also have the RMB, the mutation with T31 mutation patient only, that we can do the single arm design with 48 patients. So I think the total Polaris 2 is 333 patients enrolled well, and then the six-month MMR rate for the initial filing of the NDA with the FDA.
Awesome. Thank you. And last one for Veith, if I may, just if you could comment, Veith, on your OPEX trajectory and, you know, if you're getting to peak, 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 your question.
Yeah, great question, Mayank. So as I said, we reaffirmed our cash runway and we're, you know, happy that we've been adhering to our forecasted spending, you know, given the scale of our studies, you know, globally, multiple countries. And, you know, 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. Yang and Dr. Zai 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 and our balance sheet.
Operator
Of course. Your final question will come from the line of Michael King with Rodman and Renshaw, LLC. Please unmute and ask your question.
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 any urgency to do additional partnerships or other types of arrangements where you could lay off some of the capital allocation demands.
In terms of 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 fasil on board the optionality as 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 yeah i think i fully agree uh just add one more point that our current cash runway as we stated before consistently can support our r&d
plans through the end of 2027. More importantly, with non-registration trial and four global cleared by FDA and EMA, majority of this enrollment are already done. That's why you see the first six months, we have earned expense of more than 30% increase, primarily due to this heavy enrollment. But the good news is that most, you know, part of the cost is already at least more than halfway done, right? Of course, we remain open, flexible for many, you know, options for the, you know, fundraising and also partnership, other source of income. on top of our, you know, positive continued growth revenue with two product sales in China. I think we're really unique. It's not just because we have, you know, legacy and resources in China, but also steady the growing revenue income from China and looking forward for the global commercialization and 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.
Thank you all for joining us. I think this interim report, again, positioned us well to be the global player in the HEM malignancies. And 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 competitors or the a really excellent biotech company this time last year, okay? So I told my team and many investors, I said that you will be a different company by the time next year, okay? So 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.
