Ascentage Pharma Group International (6855) Earnings Call Transcript

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

Thank you. Really honored to be here at the main conference presentation for the first time. And we were supposed to do our presentation last year, but due to the planned IPO immediately after the JPMorgan meeting last year, so we had to cancel our presentation last year. So it's a great honor to be here. And this year, we have made a lot of progress. And as I said, we did a great IPO last year following the JPMorgan meeting and also led by JPMorgan last year as well. So this is really the overview of Ascentage. For some of you who may not know us before, let me go through this in a little bit more detail. Ascentage actually founded about 16 years ago, in 2009, and we are really truly global and commercial stage hematology/oncology company. We have 2 novel commercial products targeting BCR-ABL and also Bcl-2. We are one of the few dual listed on NASDAQ and the Hong Kong Stock Exchange. And up to the last financial report, we have $420 million of cash. So that will -- can support our current R&D plans through 2027. We have a very robust pipeline. We have 7 novel active clinical stage compounds targeting more than 10 indications, with about 30-plus FDA-cleared INDs, and we actually received 17 orphan drug designation by FDA and also by EMA, 4 Fast Track designation, 2 of them are pediatric. We run at the time, more than 40 clinical trials globally. I think one thing really makes Ascentage standing out is that we have global IP protection over 478 global issued patents, about 500-plus more pending applications. We publish regularly on JAMA Oncology, Clinical Cancer Research, among other peer-reviewed journals globally. Currently, we have close to 800 employees worldwide. Overall, we did or ongoing 13 global registration trials, including 4 FDA-cleared Phase III registration trials. Company is incorporated in Cayman Islands with headquarter in China, Suzhou, Rockville, Maryland and also Sydney. This is actually our headquarter in Suzhou building, the R&D center. So these are 2 novel commercial stage products with global opportunity. Olverembatinib is the third-generation BCR-ABL inhibitor approved in China for CML-CP with or without mutation and about 2 TKI, including the intolerant. And we are running 2 global Phase III studies cleared by FDA and EMA. On the right, we have Lisaftoclax, the novel orally active selective Bcl-2 inhibitor approved just 6 months ago in China for the CLL and SLL after BTK therapy. I think for this indication, we are actually the first one globally after BTK in CLL with a single agent as Venetoclax was only 17p at deletion indications. We also have 4 global registration trials with 2 cleared by FDA and EMA. We also have 4 global registrational trials with 2 cleared by FDA and EMA. This is our really the world-class innovative and a highly derisked late-stage pipeline. As you can see, the first 2 are commercial stage, targeting the variety of heme malignancies. We also have 3 other novel compounds potentially the first-in-class, these were successfully developed to the market. Those focus on FAK, focus on MDM2-p53, Bcl-2, Bcl-xl. There's no currently approved product yet globally. I think there are also 2 exciting programs targeting the PRC2 through the EED, have potential both for oncology anemia. Just about last week, we announced clearance of BTK degrader cleared by FDA for the global study. Here's a little more information about the Olverembatinib, HQP1351. As you can see, we have this product approved in China since 2021. That's why I said it's highly derisked. We already treated over tens of thousands of patients, CML with and without mutation and also Ph+ ALL. We have 3 global programs, POLARIS-2 targeting the CML with a single agent with the control arm bosutinib cleared by FDA and EMA and also POLARIS-1, first-line Ph+ for ALL patients. This is actually a great result. With the Part A of POLARIS-1 data we presented at ASH just last month, we doubled the 3-month CMR rate over like ponatinib in the same patient population. And we also received breakthrough designation by CD. We also have one small indication targeting SDH-deficient GIST. This is a monotherapy for pivotal registration trial. And this is a group of patients which has no effective therapy globally. I think really exciting to see is that even that this is a conference where there are at least 2 other peer companies are targeting the same like a CML patient population received great attention at Street. So overall CML market currently is over $7 billion or $8 billion and asciminib peak sales already increased from $3 billion to $4 billion. And Olverembatinib is strongly positioned for T315 mutation and compound mutations and could be the first choice for the late-line CML globally. There's another indication is the Ph+ ALL. It's very prevalent in Asian countries as China, Japan. Currently, there's no effective, safe small molecule drug and Olverembatinib is a global registration in the first-line Ph+ for ALL. I think the data so far in the last almost 10 years development in the clinic with the 2 guidance that we entered, NCCN guidelines and also CSCO in China. I think you can see we have a really truly differentiated efficacy profile as a single agent. We show strong -- also really safety profile in Ph+ ALL patients. The longest time patients use our drug is almost 10 years since the Phase I in 2016. And we have a 5-year follow-up for the CML patients after Phase I and also about 6 years follow-up for those in the AP patient population. And we actually had several presentations at ASH last month with strong activity in other rare disease like [ MM ], also FGFR rearrangement, CML, VP, et cetera. So basically, Olverembatinib demonstrates strong activity, especially in this slide, leading by the Dr. Kantarjian and Dr. Jabbour at MD Anderson. This is actually all U.S. patient population. The initial result already published on the ASH and JAMA Oncology. As you can see in this heavily pretreated, truly failed resistant CML patients, those who failed ponatinib, who failed asciminib and also over 30% of them have [ T31 ] mutation, okay? This is a really different patient population, as you see from some of the peers presentation at ASH or this conference. So with this heavily pretreated then almost the last line after 4, 5 line patient population, we see a greater efficacy as a single agent. You can see that in those who failed ponatinib or asciminib, will receive a single agent about 40% or 30% MMR rate. There are few patients actually fail both, ponatinib and asciminib. We still see the single-agent benefit. I think another very exciting data is what we released last month at ASH that in the Ph+ ALL, the newly diagnosed patients, this is part A of our global Phase III trial, the POLARIS-1. As you can see, in this population patients, we can have 64% MRD-negative CR rate, okay? This is almost double the same patient population ponatinib did about 34%. Of course, the control arm, the imatinib only can do about 16%, 17% CMR rate. We also have demonstrated very good safety profile. Another exciting data is really on the second-line treatment. This is in the CML-CP patients, patients who use either imatinib or one of the second-generation dasatinib or nilotinib and then immediately after the first line using the Olverembatinib. You can see MMR rate is over 40%. And actually, in the patients who in the first line use the second-generation compound do receive even better response. Another very exciting efficacy data is in this rare MM patient population with FGFR rearrangement. Currently, there's really no effective treatment. And we take quite a few efforts to enroll about 20 patients. And as you can see, they have a really robust activity, including the CMR rate and also a complete response after the transplant. Another really deep remission is in the blast phase CML patients. I think in the interest of time, I will not go into detail, but I think it is important to note is that the Olverembatinib has really broad and strong activity against almost all forms of the CML. The important data is on the safety. I think over the last couple of years, including actually, I forgot to mention, we entered the partnership under the option agreement with Takeda in about 2024, I think. Takeda is a great partner in CML and ALL globally. I think this is actually a 4-year follow-up of the registration trial we did. One thing I want to mention in China, actually, CD have a very high bar. This patient population, they have to fail all 3 TKI, okay? Majority, almost globally, all the registration trial is after 2 TKI. And this particular study, over 140 patients, majority of them had to fail all 3 TKIs, not just imatinib or dasatinib and also nilotinib in China. Of course, this is looking for the EFS as a great data. And the 4-year follow-up, as you can see, this is the safety profile. In the hematological AE, this is all grade 3 and above. Actually, over the time, because of the benefit of treatment to clear the cancer cells in bone marrow, those with thrombocytopenia, neutropenia actually reduced. The nonhematologic event are mostly grade 1 or 2. I think this is a great safety with a 4-year follow-up. Another exciting, I think, notable data is actually combination of Olverembatinib with Bcl-2 in Ph+ ALL. In this case, they use the Venetoclax because that's already approved on the market. Remarkable efficacy in the chemo-free setting. And more importantly, the longest patient follow-up in this particular treatment is over 800 days, okay? Of course, we will continue with the PI, the combination of Olverembatinib with Lisaftoclax now. These are more details of our APG-2575, Lisaftoclax. Lisaftoclax standing for life-saving [indiscernible] class and briefly always just called Lisa, okay? So as you can see, we have the first pivotal Phase II study with monotherapy in -- in the BTK failed patient population approved in China just about 6 months ago. And we are running 4 global studies, especially GLORA and GLORA-4, all cleared by EMA and FDA and major regulatory agency around the world, including Japan. I want to bring your attention to that the Bcl-2 selective inhibitor actually have really broad multiple heme malignancies. This is just list of 3 here, the CLL, AML and also the MDS. I think the MDS right now, globally no targeted drug approved by FDA in the last 20 years and it's really truly unmet medical need globally and untapped market. So our solution to those issues is that Lisaftoclax demonstrate great efficacy, entered the statistical guideline, the first time in China and also granted 5 ODD by FDA, okay? I think the notable efficacy data, I will present more details. But more importantly, I think, differentiate the first Bcl-2 inhibitor on the market in the last 9 years, Venetoclax is really the safety profile, okay? I think in all the clinical trials, over 600, 700 CLL patients and overall near 2,000 patients, we really demonstrate this safety profile over the current or only one on the market in U.S., Venetoclax. We designed from day 1, the patient-friendly daily dosing schedule, okay? And we received approval. Overall have a very low tumor lysis syndrome, some studies with 0. And then more importantly, there's no drug-drug interaction observed. This is really different than the Venetoclax even have a DDI with ibrutinib. Actually, if you know, they recently just released public data, [indiscernible] even have higher risk DDI over Venetoclax. So I think this is highly convenient for patients and caregivers. I think one of the very exciting important study is this GLORA-4 global trial in the first-line high-risk MDS cleared by FDA and EMA. We all know that VERONA trial had a negative result about -- since reported last July. And of course, that's really unfortunate for patients globally. And we are very fortunate to have Dr. Garcia Manero, the leading PI from MD Anderson and also Dr. Xiaojun Huang to lead this global study. I think you will see the data actually really different than the VERONA trial in terms of Venetoclax versus the combo with AZA. We demonstrated the data in the U.S. study actually that Lisaftoclax has strong clinical activity in AML, MDS as well as those patients who failed Venetoclax, okay? Especially in the MDS, CML, CMML patients, they -- ORR can be 80%, majority actually is a CR. In the exposed AML/MDS patients, we can also achieve about 31% ORR, okay? I think this really demonstrates truly differentiation and strong activity in AML and high-risk MDS patients. These are all U.S. and Australia studies. This is the summary of our label in China for the CLL, okay? As you can see, we are the first one, the only one with this daily dose ramp-up design, okay? We have only 3 dose strengths, okay, 5 days combination to the target dose and maintain, okay? I think this is the unique strength and also really convenient for patients with CLL. With a single agent after BTK in CLL, actually, this is the first indication approved globally. I want to also share with you some of the data. Actually, in this patient population, we did a pivotal Phase II. Again, CD has a high bar. They gave us this pivotal Phase II trial design 4 years ago, but a really high bar. They want -- every single patient at that time had to fail the BTK, okay? At that time, BTK was not very commonly used in terms of first line, right? It took us a while to recruit these 77 patients. But also, you can see the data, these patients are really sick patients, right, in terms of [ TP53 ] mutation, 17p deletion and chromosome -- complex chromosome. And then we demonstrate that we can achieve over 62% ORR and also really meaningful MRD negativity and the PFS as well. So -- and then they -- currently, they still observed in the PFS and OS. The data also had an oral presentation at ASH last month. The safety is also really good with those patients. But in the interest of time, I will not go through the details already presented at ASH. But more importantly, moving forward, I think, Bcl-2 is really -- can serve as a backbone across major -- many B-cell malignancies. This is also an example, we can do the combination with our own small molecule drug, such as with Olverembatinib or our MDM2-p53 inhibitors, either in AML or DLBCL, okay? I want to point it out that majority of Bcl-2 inhibitor resistance actually is due to the Mcl overexpression, not due to the mutation, right? So any drug can combine, indirectly reduce -- inhibit Mcl-1 will have a synergistic effect. And we are the only company that has those small molecule drug globally. We also have many other interesting novel pipeline. This is our BTK degrader, APG-3288. I want to point it out, actually, we moved this product very quickly from this decision to go to the program and from the PCC to the IND clearance in less than 2 years. And actually from the PCC declaration, the IND-enabling study to the IND clearance in about 8 months. And we also have other program like APG-5918. This is the epigenetic therapeutic program targeting the PRC2 via the EED. There's multiple indications in heme malignancies besides lymphoma, myeloma and also solid tumor in prostate cancer and more also additional indication in anemia. This is the data we presented at ASH last month, preclinical data demonstrated the combination with IMiD in the multiple myeloma. I think one of the benefit of this epigenetic target is really to correct this deregulation and restore the function of other important compound, including those in the prostate cancer. This is one example of the activity in CKD anemia model. In China, we already finished healthy volunteer SAD, MAD, completed about the 3-dose cohort in patients with thalassemia. China doesn't have much sickle cell anemia patients. So that's where we see initially clinical proof of concept in the anemia patients. The last one is the APG-2449. This is a triple kinase inhibitor targeting both FAK, ALK and ROS1. For the ALK, ROS1, we actually received clearance for Phase III registration trial in China. But I think more exciting is maybe on the FAK as well. But in terms of non-small cell lung cancer, this particular triple kinase inhibition may also offer the benefit because FAK overexpression is related to the ALK inhibitor resistance. And the last one is a tough target, but we have continued our effort is the MDM2-p53. There are many companies working on that, and we have been also working on that for the last 10 years, including multiple Phase II studies. And currently, we are looking for the path for the registration trial with some really truly clinical unmet medical need in the ACC or some of the pediatric sarcoma patients. So the last one is we also work a long time is the dual Bcl-2, xL inhibitor. This takes a while to develop in the clinic. I think the other peer drug, navitoclax actually stopped all the studies due to some of the target toxicity in the platelets. We solved this problem preclinically by making the prodrug, but still need more study in terms of regulatory path to the NDA. So in the interest of time, I will not go to that much detail. I think finally, this is a very exciting time to summarize our achievement last year. I think 2025 has been tremendous important year for Ascentage. We achieved the first goal being listed on NASDAQ and also get NDA approval for the Bcl-2 selective inhibitor, Lisaftoclax and also received 2 important clearance from FDA and EMA because these 2 trials are the first-line patients. And for MDS, we are globally the only Phase III studies for the MDS patients, and we are really moving fast on the GLORA-4 enrollment. And POLARIS-1 again, is Ph+ for ALL patients for the first line. And of course, we do everything we can to advance enrollment all these POLARIS and the GLORA registration trial studies. I think thanks to my team, we work very hard behind the scene. As I'm presenting here, all the major achievements come from our team's effort. Looking forward to the 2026, I think the first and most important one is focus on execution, complete the enrollment for all the registration studies. And also, of course, we will have a continued growth and reach out to more patients in our commercialization effort. And we're looking for the NRDL coverage for Lisaftoclax and advance our BTK protein degrader and also the EED inhibitor in oncology and also anemia, both U.S. and China. I think there's a lot of excitement to come from Ascentage team this year. And finally, I think I want to enter this slide that from day 1, we focus on the patient, focus on the global market. Right now, actually, you can see there's one missing we have 7, what we call 7 magnificent small molecule drug with 2 already late stage. One day, one of the analysts told me we should refer us as a super late stage. So we have 2 super late-stage global opportunity products. And actually, with the BTK degrader, we're going to target all major 3 lineages of heme malignancies from the CML, ALL, CLL, AML, MDS, multiple myeloma, DLBCL and also anemia. I think more importantly, we are probably the only company have this chemo-free oral active small molecule drug can do the combination, right? So the combination of our Bcl-2, Olverembatinib, BTK degrader plus other one like EED inhibitor and the MDM2-p53, we are probably the only company who will be able to have this novel single-agent compound and also combination to help the patients globally. Finally, I thank you all for attending, and I'd be happy to answer the questions. Thank you.

Thank you, Dr. Yang. Thank you so much for joining us. Welcome. Let's start the Q&A. For those who are in the audience, if you have any questions, feel free to raise your hand. And for those joining us virtually, you can also submit questions on the portal. Dr. Yang, first time on the main track at the conference, so welcome. Ascentage had been such a strong performer last year out of the NASDAQ IPO. How do you think about where you stand today from a strategic standpoint? I think part of the observation that we see is that U.S. investors haven't gotten to fully know the story, right? So how do you think about getting traction with investors? How do you think about maintaining your strong position also from a liquidity standpoint as well?

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

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

Great question. I think the BTK degrader first demonstrated our R&D capabilities. We entered -- designed that program and then getting the PTC in less than a year. And from PTC to getting the -- filing the IND about 7, 8 months and received the IND clearance within 30 days through the FDA. And we're looking for -- this is public information that CD already put on the website, starting the clock. Nowadays, CD can be getting IND cleared by 14 days, 14 working days. I think this is the first time for us to getting the true novel degrader into the clinic. But more importantly, I think with the BTK degrader, first, in terms of clinical program, they will take care of all these inhibitors covalent, non-covalent or mutation or not. That's very important, right? Second, this will allow us to have a combination with our Bcl-2 inhibitors, especially. And also, more importantly, we will demonstrate probably more potential moving forward in the lymphoma. So always using this as the analogy of having Army, the Navy and the Air Force working together to target 3 lineages of heme malignancies, lymphoid, myeloid and lymphoma. And then we have all these 3 orally active targeted small molecule drugs.

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