Ascentage Pharma Group International

Good day and thank you for standing by. Welcome to the Ascentage Pharma 2025 interim results presentation and conference call. At this time all participants are in listen only mode. After the speaker's presentation there will be the question and answer session. To ask a question during the session you need to press star 1 1 on your telephone keypad. You will hear an automatic message advising your hand is raised. To withdraw a question please press star 1 and 1 again. Please be advised that today's conference has been recorded. I would now like to hand the conference over to our first speaker today, Hogan Wang. Please go ahead, sir.

Thank you, operator. Good morning and welcome to today's call. As a reminder, the company's remarks today corresponds with the earnings release that was issued on August 20th evening U.S. Eastern Time. In addition, recording of today's call and the PowerPoint presentation will remain available on the Centage website within the investor relations section shortly following the conclusion of this call. As part of today's call, I'll go over some of the Sage Harbor statements. We'll be making certain forward-looking statements based on our current expectations. These statements are subject to numerous and uncertainties that may cause actual results to differ materially from what we expect due to a variety of factors, including those discussed in our SDC filings, including 20F. Should any of these risks materialize, then the assumption may be proven to be incorrect and the actual results may vary from what was mentioned in the forward-looking statement. On today's call, I'm joined by Dr. Da Jun Yang, Chairman and CEO, who is going to provide an overview of recent developments and performance for the first half of 2025, as well as Dr. Veet Mishra, CFO, who will go through the financial highlights. The presentation will then be followed by a Q&A session. During the Q&A session, the team will be joined by Dr. Yifan Zhai, Chief Medical Officer, Dr. Xiaomeng Wang, Co-Founder, Chief Scientific Advisor, Mr. Eric Huang, Senior Vice President of Global Corporate Development and Finance, and lastly, Dr. Zhihao Si, Head of Commercial. With that, I will now turn the line over to Dr. Yang.

Thank you, Hogan. Hello, everyone. I'm Dejing Yang, Chairman and the CEO of Ascended Farmer. Thank you for joining us today for Ascended Farmers 2025, first half year business summary and the financial review. Ascentage has continued strong momentum in its business performance year to date. Sales of oral martinib in China grow significantly at 93% year over year, driven by the NRDL coverage expansion, which is substantially improving affordability of the drug And we have also made a lot of progress in improving patient access, with a 47% increase in the number of hospitals where Orenbutynib is on formulary. This is compared to over the last year. We expect sales of Orenbutynib to continue to grow. In July, Lisovacast was approved by the China MMP-8. making it is the first VCL2 inhibitor approved for CLL in China, and the second VCL2 inhibitor approved globally. The Silvercast is a novel VCL2 slack inhibitor developed by us internally, and is our second market product. The Silvercast approval, once again, demonstrate our research and development capability, and our relentless pursuit of developing and marketing drugs that address unmet medical needs. Now, with the two innovative hematological oncology products on the market, we have developed a tailored dual-engine commercial strategy through which we will expand our team, leverage our existing commercial infrastructure. We will focus on accelerating the silver cost of market entry and the beauty market leadership. I will talk about the commercial strategy later in our presentation. We continue to execute our global clinical programs. We continue to enroll patients in our registration of trials, including the three Polaris and the four Glora trials. Earlier this week, we announced that our Glorafor trials for first-line high-risk MDS has been cleared by the US FDA and EMA, with the first patient already those in Europe. In terms of our financial position, we have further strengthened our balance sheet. In addition to our NASA IPO in January, we have raised US $190 million in July. With the proceeds, our pro forma cash balance reached approximately US $420 million. With we join us recently as a CFO, we will deepen our engagement with global investors and further optimize our balance sheet and the cash management. Product sales of Orambutinib in China grow 93% year-over-year in first half 2025 to US dollars 30.3 million. We benefit from the expanded coverage by NRDL. Starting from the beginning of the year, all the approved indications have been covered by NRDL, including the CMLCP patients who are resistant and or intolerant to first and second generation TKI, regardless of T315 rotation status. This is an early but important success driven by improved affordability with much broader patient coverage by NRDL. We expect there'll be more patients switching from over-impartial now over time. Additionally, we made significant progress of accelerating hospital access, with a 47% increase in the number of hospitals over the last year. This is really significant. Going forward, we expect sales of our martini in China to continue to grow, driven by multiple tailwinds. We'll continue to further penetrate and increase our market share with the expanded NRDL coverage. We expect more patients to switch to ovarian bactinib, and the patient will stay on treatment for a longer time as ovarian bactinib is safe and well-tolerated. On the PSG positive AI front, we continue to make progress at advancing Polaris I, which, if successful, will make ovarian bactinib the first TKI for first-time pH-positive ALL in China. We have received a work-through therapy definition for pH-positive ALL from China CDE. Oral martinib is now included in Cisco 2025 recommendations with a level one status for both pH-positive ALL and CML, which will help us further in promotion. In July 10 this year, Lisovacast was approved by China's MMP8 for the treatment of adult patients with CLSL who had previously received at least one systematic therapy, including BDK inhibitors. The approval makes Lisovacast the first BCR2 inhibitor approved patient with CLSL in China, and the second BCR2 inhibitor approved globally. With this approval, The server cards address an urgent unmet medical demand, offers a much needed alternative for CLL patients, especially those who do not respond well to BDK or CIT, and effectively fills the void for BCR2 inhibitor for CLL, SIL in China. We are pleased to highlight that in this approved indication only requires patients to have received one prior line of treatment without specifically requiring patients to be refractory or resistant to prior treatment. This will allow more patients to benefit with a reserve cost at an earlier time. We have efficiently commercial sales in China with the first prescription written within just 15 days after approval. We have established distribution channels effectively by teaming up with all top national distributors. With two key products on the market in China, we have established a strong product portfolio in hematological oncology. Under the leadership of Zhi Chao, our head of commercial, we will execute our dual-engine commercial strategy. Since our launch of our martini in 2021, we have established robust and comprehensive commercial infrastructure in China. For the server class, we will leverage on the existing team, while further expanding it to build a fully in-house and nationwide team. We actually more than doubled our commercial team just in a couple of months. We will continue to capitalize on NRLDL's listing for over-emphasis to drive sales growth, while leverage The Silvercast is the first mover advantage to rapidly establish the market leadership. Now let's look at summary of our innovative pipeline. We are advancing six product candidates globally. Orembo Teneb and the Silvercast are approved in China and are running registration trials in US, China and Europe. In addition, we have four other novel compounds in the pipeline. APG2449 is a small molecule APK ALK and ROS1 triple kinase inhibitor. This is very novel. We are conducting Phase III registration of trials for ALK-positive long-term muscle lung cancer in China. APG115 is a small molecule MDN2-PP3 inhibitor in Phase II development in U.S. and China. In this year's ASCO, we published data on ACC and other solid tumors. APG1252 is a small molecule, dual BCR2 and XL inhibitor, in Phase II development for various cancers in U.S. and China. APG5918 is an EED inhibitor. In this year's AACR and EHOP, We have published data that show anti-tumor effects in preclinical models of castration-resistant prostate cancer and the T cell lymphoma. We are also conducting phase I trials on anemia patients. Now let's focus more on O1-Bartenev. For O1-Bartenev, we are currently conducting three rejection trials, including Polaris II, an FDA-created trial as a monotherapy for CML with and without T315 mutations. Polaris-1 that evaluates Ormaltilib in combination with chemotherapy for the treatment of a frontline phage-positive ALL. If approved, it is expected to become the first TKI for first-line phage-positive ALL in China. Polaris-3 that evaluates Ormaltilib as a monotherapy for STG-deficient Gs. CML and AL are large markets. It is estimated more than US $40 billion annual market combined. There are significant unmathematical needs for those indications. Despite initial responses to the first and second line TKI, many CML and AL patients develop mutations, resistance, or intolerance. Panadolib and Acinib have its own shortcomings, such as safety issues and the weaker effects and mutations limiting their potential. Ovamartinib is designed to address those unmet medical needs. Differentiated from other BCI-ABO inhibitors, with its favorable safety profile and efficacy, it is the first third-generation TKI approved in China. and the only third generation TKI covered by China NRDL. Ourobatinib have strong inhibition for the majority of BCR-ABL mutations and those compound mutations, allowing it to be overcome many difficulty resistance. It has demonstrated favorable clinical benefit in heavily pretreated patients, particularly prolactinib or acetaminophen patients as well as those of harboring T3-1,5 mutations. We also published data that Orvimartinib can overcome patients who felt both Panartinib and Acinimib in U.S. trials. Long-term safety has also been demonstrated in a five-year follow-up with 73% of CMR patients' continued treatment. This was published a couple years ago on ASH oral presentation. Orenbautinib clinical benefit, particularly in overcoming ponatinib and oracinib resistance, were published on JAMA oncology. In a trial led by Dr. Jabou from MD Anderson Cancer Center, Orenbautinib was investigated in heavily pre-treated patients. Among those patients, You can see that 29% had T315 mutations. 50% received more than four TKIs. 50% were pronotinib pre-treated. 27% were cinnamon pre-treated. ORN button was well tolerated. The median treatment duration of CML-CP was 48 weeks. and the longest treatment in that trial reached more than three years. All macronutrients show strong anti-leukemia activity regardless of mutation status and the prior treatment was a ponatinib or acetaminophen. All patient groups, including T315 mutants and the ponatinib or acetaminophen resistant patients demonstrated more than 50% in CCYR and more than 30% in MMR. Even CML patients who felt both ponatinib and acinib can benefit from Orambutanib. This is really impressive. At the 2024 ASH, we presented data for second-line therapy in CML CP patients, majority of which received second-generation TKIs as a first-line treatment. In patients who have been treated with second-generation TKI in the first-line setting, Orenbutynib demonstrated a CCYR rate of 78.9% and an MMR rate of 43.5%. Those data added to our confidence that Orenbutynib may be a viable second-line treatment option for patients with CML, especially for those who are failing on second-generation TKI in the first-line setting. For pH-positive ALL or Ratinib in combination with low-intensity chemo or Blink-Syto also demonstrated deep and a profound response. Patients were able to achieve 100% OR or CMR in as quickly as three months. Based on those real-world data, oral martinib will potentially offer a chemo-free and a transplant-free treatment option to revolutionize the treatment paradigm of ALL patients. At ASH2024, oral martinib and the SilverCast synergistically demonstrate promising clinical benefits as a chemotherapy or immunotherapy-free regimen for children with RR-pH-positive ALL. 83.3% OR was observed at the end of a combination therapy with a fixed duration regimen with no drug-drug interactions. Moving to our second lead asset, Lisovacus. As a recap, Lisovacus was approved by China MMPA in July for adult patients with CLSL. We are currently conducting several registrational trials including Glora, an FDA-clear regurgitational phase three trials, in combination with TKI inhibitors for CLSL patients, previously treated with BDK inhibitors. This is an add-on strategy, or 1.5 line, actively enrolling globally. Glora 2, evaluating the lower class, in combination with Acala-Bruzolib, as a frontline treatment for CLL and SRL. Glora 3, evaluating the total cost in combination with AZA for the frontline treatment of elderly or unfit AML. And very importantly, Glora 4, evaluating the total cost in combination with AZA as a frontline treatment for high-risk MDS. This is just recently cleared by FDA and EMA. So we are conducting four trials of ResultCast globally. We are also conducting phase two trials, ResultCast, for MN in US and China. Now, let's talk a little more about GlOR4 trials, recently cleared by FDA and EMA, and actively enrolling globally. This study was originally approved by ChinaCD in 2024. This is a multi-region, multi-center, randomized, double-blind, phase III trials to evaluate the efficacy and the safety of the server costs. combo with the AZA compared to AZA alone in a newly diagnosed adult patients with higher risk MDS. We are really excited that with the FDA and the EMA clearance, this represents the only DCR2 inhibitor in a phase three global registration trial for MDS. Patients are already enrolled in China and Europe. This trial is co-lead by Professor Xiaojun Huang from Peking University Hospital and Dr. Garcia-Monero from MD Anderson. There is a large unmathematic need for MDS patients, as there's no approved targeted survey in the last 20 years. The current standard of care, HMAs, only yield about 30% to 40% OR, and the CR less than 20% for first-line patients, and the five-year survival rate for high-risk MDS patients are only about 16% to 24%. If successful, Lasocas may become the world's first BCL2 inhibitor approved for the treatment of first-line high-risk MDS. Another very important thing is that this protocol combination with the AZA versus AZA alone is the same for US, Europe, and China. This is a very unique opportunity for the disabled class clinical development. BCR2 is a critical target for many hematological malignancies. In CLL, limited adoptions of another class combination leaves a large opportunity for lethal cuts. We are actually the first B-Shot inhibitor as proved for broader CLL indications. And the Venetocost only approved for the 70P deletion as a single agent in US and China. In AML, Venetocost plus AZA is widely used for elderly or unfit patients. but there's no effective treatment for those who fail Venetocast. In MDS, currently, Verna trial is negative, so no approval for target therapy in the last 20 years in MDS. And the Lizocast now is the only visual inhibitor in a phase three registration trial. Similarly, in MMM, Venetocast failed two phase III trials a couple years ago. These remain incurable with a higher rate of relapse and disease progression. As you can see, each one of these indications represents significantly un-mathematical needs and also hundreds of billions of market opportunities. The third class is globally the second BCR2 inhibitor under clinical trials. about seven, eight years ago. We have treated more than thousands of patients, demonstrate unique. Those are not strategy benefit, as we see in the CL, ML, MDS, and MM patients, including those patients who fail over another class. Resolver class, or APG 2575, is globally the second BCR2 inhibitor under clinical studies about seven, eight years ago. Now we have treated over 1,000 patients in CIL, AML, MDS, and MN, including those who failed or progressed on another class. And the VDK inhibitors offer much needed treatment alternatives. From day one, we designed Because of the shorter T half, actually, we demonstrate very good tolerability, lower incidence of neutropenia, thrombocytopenia, and infection, and also have much lower risk of TLS. No drug is used to treat TLS. Drug interaction was observed with any BDK inhibitor or other therapeutic agents, such as anti-infectant, which makes combination with those drugs possible. This is an important clinical differentiation. Reserve cards are the unique and the only patient-friendly daily dose-turn-up schedule. Compared with the vanilla cards that require weekly dose-turn-up, will take about five to eight weeks to complete. Patients on the silver class can achieve those target dose within five to six days. Patients undergo daily dosage and up for five days, basically 20 milligram on day one to 400 milligram on day five. Starting from day six, patients on the target dose of 600 milligram in the case of a single agent treatment. Also, no BDK need-in is required for debulking, which further shortens the initial dose turn-up. That means we can offer the patients the best treatment regimen early on. Notably, those daily dose turn-up schedule does not result TLS. The daily dose turn-up schedule offers superior convenience to patients and the doctors. allowing patients to achieve a target dose and a possible start combination much sooner. In all RRCL patients, this overcast demonstrated favorable clinical benefits and the tolerability profile as a single agent and in combination therapies. In combination with Akana, it was active in both treatment-naive and RRCL patients with an OR of 98%. For the 14 patients with prior venetoclastic rupture, the combined result is 86% OR. In long-term follow-up, no DDIs, no new safety findings were observed. In combination with the AZA in AML, lithoclasts demonstrate clinical meaningful OR and tolerability in patients. In RR-AML patients, OR and CR were 72.7% and 45.5% respectively. In first-line elderly unfit AML patients, ORR and CRC were 64.1% and 51.3% respectively. Similarly, the Zolocast showed favorable safety profile with no TLS reporting and low early mortality. In an oral presentation at ASCO this year, The results demonstrate clinical meaningful OR and tolerability in venetocast failed AML patients. Although two-thirds of those first-line patients received VEN plus ADA achievable CR or CRI, the remaining one-third failed to respond, and over half of those responders eventually relapsed. These venetocast failed AML patients. has very limited treatment options or no options. Lisovaclus combo with AZA could achieve 31.8% OR for patients relapse or refractory after venous cast treatment. Lisovaclus plus AZA was well tolerated with a few dose modifications and a low infection rate. In MDS, as reported in 2024 ASH, Lisovacus combo with AZA has the potential to effect deeper and more durable response. Meaningful ORR and favorable tolerability profile were observed in treatment-naive MDS. In 23 patients with treatment-naive MDS treated with Lisovacus and AZA, the ORR rate was 33.9%, and the CR rate was 30.4%. There's no 60-day mortality, much fewer dose reductions, and no dose discontinuation, and comparably low infection rates. No tumor lysis syndrome was reported. In an oral presentation at ASH2024, these overcasts, together with the Pondax, show the clinical benefit in RR multiple myeloma and amyloidosis patients. regardless previous use of anti-CD38 antibody. The combination of the several kinds of Pondax resulting in OR of more than 60% in all RRMM patients and those pre-treated with anti-CD38 antibody. The median PFS were 9.7 months for those patients as reported at ASH last year. There were no observed DDIs and very limited hematological side effects. With the excellent efficacy and the safety data in MN patients, lesophocasts may be able to overcome the challenges of another class facing MN in two previous phase three trials, basically safety and a DDI issue. Those are really clinically significant LiSERVA has the potential to combine with all other pipeline products, such as the MDN2-PP3 inhibitor APG105, and also BCR-EPO inhibitor . Especially in the preclinical models of AML, LiSERVA combo with APG105 demonstrates the genetic effect in the AML and also induces synthetic lethality with the potential to overcome another cause of resistance. The HERC-Cas combo with Orenbachtinib, which can also inhibit the FLIRT3, may have a synergistic effect on FLIRT3-ACD mutant AML. The combination of the two may synergistically inhibit cellular proliferation and induce apoptosis, overcome another cause of resistance. by down-regulating MCR1. Looking ahead to the second half of 2025, we will continue the expansion plan of commercial organization, execute the dual-engine commercial strategies. We will continue the sales growth momentum of our maintenance through improved affordability, increase the number of patients on treatment, and the lengthening duration of therapy. Leveraging the server-class product differentiation and the first-mover advantage will deepen market potential and improve patient access. We'll continue to carry out our ongoing registration trials, particularly the GLORA4, for the treatment of high-risk MDS, which clearly demonstrates benefits in the clinical setting and recently cleared by FDA and EMA. And importantly, we're using, we're taking the same protocol for registration trial in U.S., Europe, and China. We plan to commence the registration trial for the first-line Th-positive ALL in the U.S. as well. Now I will turn the presentation to Wei, our CFO, about the financial summary. Weed, please.