refractory chronic myelocytic leukemia

ROCKVILLE, Md. and SUZHOU, China, Sept. 13, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that it has released the clinical data of olverembatinib (HQP1351), the company's novel drug candidate, in patients with succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST), in a Mini Oral at the 2024 European Society of Medical Oncology (ESMO) Congress. These data of olverembatinib, presented in the Mini Oral at ESMO 2024, showed sustained clinical benefit in patients with SDH-deficient GIST. As of March 12, 2024, six of the 26 patients with SDH-deficient GIST enrolled in the study achieved partial responses (PRs). The objective response rate (ORR) was 23.1%, and the median progression-free survival (PFS) was 22 months. Furthermore, studies on mechanism of action (MOA) revealed that olverembatinib exerts its antitumor activity by modulating multiple signaling pathways involved in angiogenesis, apoptosis, proliferation, and survival. Olverembatinib, a novel orally-administered tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma, is the first approved third-generation BCR-ABL inhibitor in China. To date, olverembatinib has been approved for two indications in China, including adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first-and second-generation TKIs. Olverembatinib is jointly commercialized in China by Ascentage Pharma and Innovent Biologics. This is a study of an investigational drug not yet approved by the US Food and Drug Administration (FDA). In addition to hematologic indications, olverembatinib is also being clinically evaluated for the treatment of GIST. To date, olverembatinib has already been granted a Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) for the treatment of patients with SDH-deficient GIST who had received first-line treatment. Recently, olverembatinib was cleared by the China CDE to enter a registrational Phase III study in patients with SDH-deficient GIST. Prof. Haibo Qiu, of Sun Yat-Sen University Cancer Center, and the presenter of the report, commented, "SDH-deficient GIST is an extremely rare type of cancer. According to Chinese and International clinical guidelines, there are currently no standard treatment options for unresectable SDH-deficient GIST. In this Phase I study, we have observed encouraging clinical benefit data and further explored the MOA of olverembatinib. Supported by existing data, we will soon initiate a registrational Phase III study in efforts to bring a new treatment option to more patients with SDH-deficient GIST." Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "Clinical data presented in the Mini Oral reaffirmed olverembatinib's clinical benefit and favorable tolerability in patients with SDH-deficient GIST, thus indicated another potential breakthrough for an indication with a huge unmet medical need. We will actively advance this clinical development program which hopefully will soon offer patients a safe and effective new treatment option." As one of the world's leading and most influential oncology congresses, the ESMO Congress showcases the latest results in some of the most cutting-edge cancer research from around the world. Highlights of the data on olverembatinib presented at this year's ESMO Congress are as follows: Updated efficacy results of olverembatinib (HQP1351) in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and potential mechanisms of action (MOA) Format: Mini oral Presentation#: 1722MO Category: Sarcoma Date & Time: Friday September 13, 2024, 16:30 - 16:35 CEST Speaker: Haibo Qiu, MD, PhD, Sun Yat-sen University Cancer Center Highlights: Background: SDH-deficient GIST is a rare disease with limited treatment options. The oncogenic mechanism of SDH deficiency has not been elucidated. Olverembatinib, already approved in China for the treatment of adult patients with TKI-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP), with or without the T315I mutation, has shown promising clinical efficacy in SDH-deficient GIST. This report provides the most updated Phase I efficacy data and translational data of olverembatinib in SDH-deficient GIST. Methods: This study (HQP1351-SJ0003; NCT03594422) was designed to evaluate the safety and efficacy of olverembatinib in patients (≥12 years of age) with GIST or other solid tumors. Olverembatinib was administered orally every other day (QOD). The study evaluated the clinical efficacy of olverembatinib and analyzed the drug's MOA using multiple in vitro and in vivo assays including a SDHB knock-down rat pheochromocytoma PC12 (#5F7)-derived mouse xenograft model. Enrolled Patients: As of March 12, 2024, a total of 26 patients with SDH-deficient GIST (confirmed by IHC) were treated with olverembatinib, including 25 (96.2%) who had received 1 to 4 TKIs and 13 (50.0%) who had received ≥3 TKIs. Efficacy and Safety Results: Olverembatinib was well tolerated at doses of 30 to 50 mg. In all, 6 (23.1%) patients achieved partial responses (PRs) and the median PFS was 22.0 months (range: 12.9-38.6). Preclinical Results: Olverembatinib had superior antiproliferative activity (vs. other approved TKIs) in SDHB-deficient cell lines (IC50, 0.129-5.132 μM). In PC12#5F7 (SDHB knock-down) cells, olverembatinib decreased HIF 2α, VEGFA, and FGFR1 protein levels and inhibited phosphorylation of FGFR1, IGF 1R, SRC, AKT, and ERK1/2. In PC12#5F7-derived xenograft models, olverembatinib demonstrated dose dependent antitumor activity at 10 and 20 mg/kg (QOD). Conclusions: Olverembatinib showed sustained clinical efficacy in SDH-deficient GIST, indicating potential benefit of this treatment as well as providing a benchmark for future studies in this rare subtype of GIST. MOA studies revealed that olverembatinib exerts antitumor activity by modulating multiple signaling pathways involved in angiogenesis, apoptosis, proliferation, and survival. About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ROCKVILLE, Md. and SUZHOU, China, Aug. 22, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies for malignancies, today announced its 2024 interim results. During the reporting period, Ascentage Pharma continued to execute its global innovation strategy, having achieved breakthroughs across various aspects of its business including external collaborations, commercialization, and clinical development. In particular, the company has set a new record with its revenue for the first half of 2024 and reported profit for the first time. During the reporting period, Ascentage Pharma has set a new record for its revenue that grew by 477% from the same period last year to RMB824 million, with most of the revenue generated from sales of pharmaceutical products and license income. For the very first time in its history, Ascentage Pharma reached profitability, having reported a net profit of RMB163 million. Ascentage Pharma made rapid progress with the commercialization of its first approved product, olverembatinib (HQP1351). During the reporting period, olverembatinib generated a sales revenue of RMB113 million, which grew by 120% from the second half of 2023 and 5% year-over-year. Ascentage Pharma and Takeda, a multinational pharmaceutical company, have entered into an exclusive option agreement that granted Takeda an exclusive option to enter into an exclusive license agreement for olverembatinib. Once exercised, the Option would allow Takeda to license global rights to develop and commercialize olverembatinib in all territories outside of, among others, the mainland China, Hong Kong China, Macau China, and Taiwan China. Ascentage Pharma has received US$100 million in option payment and a US$75 million equity investment. The company's cash flows continued to improve. As of June 30, 2024, the company's cash balances were RMB1.1 billion and rose to RMB1.8 billion by early July, 2024. Entered into a landmark global collaboration that is the largest BD deal among small molecule oncology drugs in China Ascentage Pharma constantly seeks global partnerships. During the reporting period, the company and Takeda, a multinational pharmaceutical company, entered into an exclusive option agreement for olverembatinib. This collaboration, with a total value reaching US$1.3 billion, includes an option payment of US$100 million and an option exercise fee and potential milestone payments totaling US$1.2 billion. Additionally, Ascentage Pharma is eligible for tiered double-digit royalties on annual net sales. To date, this is the largest out-licensing deal for any small molecule oncology drug in China. Furthermore, Ascentage Pharma also received an equity investment from Takeda. This collaboration highlights the significant clinical and commercial potential of olverembatinib in the global market and laid a solid foundation for the future global commercialization of the drug. Ascentage Pharma has already received the US$100 million option payment and US$75 million equity investment from Takeda. Commercialization of olverembatinib accelerated and strengthened the company ' s revenue generating ability Following the inclusion of the first approved indication of Ascentage Pharma's novel drug candidate olverembatinib into the China National Reimbursement Drug List (NRDL) in January 2023 and the regulatory approval for its new indication in November 2023, olverembatinib continued to realize its growth potential while boosting company's ability to generate revenue through product sales. During the reporting period, the sales revenue of olverembatinib grew by 120% from the second half of 2023 and by 5% year-over-year, to RMB113 million. Ascentage Pharma is expeditiously expanding the commercialization of its approved product. As of June 30, 2024, olverembatinib has entered 670 hospitals and direct-to-patient (DTP) pharmacies nationwide and its number of listed hospitals has grown by 79% compared to the end of last year. Since the approval of its new indication in November 2023 till June 30, 2024, olverembatinib has been included into 114 supplemental insurance for major diseases and Huimin insurance plans of 20 provinces and 83 municipalities. Additionally, olverembatinib was included into the special drugs catalog of the Huimin insurance plan of 20 provinces and municipalities such as Hebei, Hainan, Inner Mongolia Autonomous Region, Wuxi, Huzhou, Shenzhen, and Yantai, which greatly improved the drug's accessibility and alleviated the burden on patients. As the first China-approved third-generation BCR-ABL inhibitor, olverembatinib's clinical value and therapeutic potential continued to received high profile recognition during the reporting period, both in China and globally. In January 2024, clinical trial results of olverembatinib were included into the US National Comprehensive Cancer Network® (NCCN) Guidelines for the Management of Chronic Myeloid Leukemia (CML). Moreover, olverembatinib has received upgraded recommendations from the 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Hematologic Malignancies in CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), plus a number of additional Level I recommendations from the guideline. In July 2024, olverembatinib was approved in Macau China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs, marking another major milestone for olverembatinib following initial approvals it received in the Chinese mainland. Global innovation strategy yielding more encouraging results with eight registrational studies being simultaneously advanced Guided by its global innovation strategy, Ascentage Pharma delivered multiple milestone achievements and swiftly advanced its global clinical development programs during the reporting period. To date, two of the company's key drug candidates, olverembatinib and lisaftoclax (APG-2575), have been cleared to enter 11 registrational studies, including 3 registrational studies that have been completed and 8 registrational studies currently ongoing. In February 2024, olverembatinib was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study in previously treated adult patients with CML-CP. This is the first FDA-cleared registrational Phase III study of olverembatinib and it represents a big step forward for Ascentage Pharma's global clinical development in hematologic malignancies. Outside hematology, the Center for Drug Evaluation (CDE) of China's National Medical Product Administration (NMPA) cleared a global registrational Phase III study of olverembatinib in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had failed prior systemic treatment. This clearance represents a crucial step in Ascentage Pharma's clinical development in solid tumors. Meanwhile, Ascentage Pharma also made notable strides with the clinical development of lisaftoclax in hematologic malignancies. During the reporting period, the China CDE cleared a Phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS). This is the fourth cleared registrational Phase III study of lisaftoclax. Winning recognition from around the world with robust clinical data spanning multiple indications As an innovative biopharmaceutical company focused on global innovation, Ascentage Pharma has built a high value pipeline composed of assets with first- and best-in-class potentials and conducted more than 40 clinical trials in China, the US, Australia, Europe, and Canada. In this process, Ascentage Pharma made steady progress exploring and validating a number of its drug candidates across multiple indications and presented updated results from its clinical programs at a number of international congresses, showcasing its prowess in R&D and clinical development. During the reporting period, results from four clinical studies of olverembatinib, lisaftoclax, and APG-2449, the company's three key drug candidates, were selected for presentations at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. This is the seventh consecutive year for Ascentage Pharma to present at the meeting. Among these results, the data of olverembatinib in patients with TKI-resistant SDH-deficient GIST were selected for an Oral Report. In the data, olverembatinib showed promising clinical benefit including a clinical benefit rate (CBR) of 92.3% and a median progression-free survival (PFS) of 25.7 months in patients with SDH-deficient GIST, an indication that currently lacks standard of care treatment. At the same meeting, Ascentage Pharma presented the latest data that further demonstrated the therapeutic potential of its FAK/ALK/ROS1 TKI APG-2449 for the treatment of non-small cell lung cancer (NSCLC). At the 2024 European Hematology Association Hybrid Congress (EHA 2024) which took place in June this year, Ascentage Pharma released update results from five studies of olverembatinib, lisaftoclax, and APG-5918, three of the company's key drug candidates. These data highlighted the company's competitiveness in the field of hematologic malignancies. The three studies of olverembatinib presented at EHA 2024 include one that reported the latest median 1-year follow-up data of olverembatinib in patients with CML and Ph+ ALL, updated from the data released at the 2023 American Society of Hematology (ASH) Annual Meeting. In the results, olverembatinib showed excellent durable clinical benefits and favorable long-term tolerability in patients who had been treated with multiple TKIs (including those who were resistant to ponatinib and/or asciminib), regardless of whether they harbored the T315I mutation. The latest data from multiple studies of lisaftoclax were also selected for presentations at the 2024 ASCO Annual Meeting and EHA 2024. These results highlighted lisaftoclax' therapeutic potential in a range of hematologic malignancies. Data released at this year's ASCO Annual Meeting include the latest promising results from a Phase Ib/II study of lisaftoclax in combination with AZA in patients with treatment-naïve (TN) or relapsed/refractory (R/R) acute myeloid leukemia (AML), and a global, multicenter Phase Ib/II study of lisaftoclax alone or in combinations for the treatment of patients with Waldenström macroglobulinemia (WM). At EHA 2024, the company presented encouraging updated data of lisaftoclax in patients with R/R multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis. Furthermore, results from three preclinical studies of olverembatinib, alrizomadlin (APG-115), APG-2449, and APG-5918 were announced at the 2024 American Association of Cancer Research Annual Meeting (AACR 2024), providing important scientific rationale for the future clinical development of these assets. Deepening global innovation while opening a whole new chapter on growth and development To support its long-term strategy and growth, during the reporting period, Ascentage Pharma has confidentially submitted a draft registration statement on Form F-1 to the US Securities and Exchange Commission (SEC) relating to the proposed initial public offering of American depositary shares (ADSs) representing its ordinary shares. Ascentage Pharma is steadfastly committed to its global innovation strategy and strengthening its intellectual property portfolio. As of June 30, 2024, Ascentage Pharma holds 520 issued patents globally, among of which 367 patents were issued outside of China. Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, said, "In the first half of 2024, Ascentage Pharma has achieved multiple milestones in global business development, product commercialization, and global clinical development. These achievements highlight our global innovative capabilities and competitiveness in the field of hematologic malignancies. During the reporting period, we entered into a global collaboration valued at up to US$1.3 billion with Takeda, a multinational pharmaceutical company, for olverembatinib, in an agreement that also includes tiered double-digit royalties on annual net sales. This is the largest BD deal for any small molecule oncology drug in China. Moreover, we have already received US$75 million in equity investment from Takeda. This collaboration is another validation of our leadership in the industry and olverembatinib's value in the global market that will hopefully demonstrate clinical potential in more conditions that currently lack treatment options. In February 2024, the US FDA cleared a global registrational Phase III study of olverembatinib, marking yet another major milestone in the global clinical development of the drug. It is worth emphasizing that during the reporting period, Ascentage Pharma achieved profitability for the first time in its history. With olverembatinib included into the China NRDL and approved for a new indication in the country, we are empowered to further strengthen our commercialization capabilities. At the same time, we made broad progress with our global clinical development programs, expanded the potential indications of our key drug candidates, and reinforced our competitiveness in the field of hematologic malignancies. Pressing ahead with our patient-centric global innovation strategy, we will continue to build out our commercialization capabilities and accelerate the global clinical development of our investigational assets. To fulfill our mission of addressing unmet clinical needs in China and around the world, we aspire to bring our innovative drugs to the global market as soon as possible for the benefit of more patients around the world and create additional value for societies and our investors." About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. The company has built a pipeline of 9 clinical-stage drug candidates, including novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma

SUZHOU, China and ROCKVILLE, Md., June 17, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that updated results from three studies of olverembatinib (HQP1351), the first China-approved third-generation BCR-ABL1 inhibitor, have been released in posters at the 2024 European Hematology Association Hybrid Congress (EHA 2024), taking place in Madrid, Spain. Building on the data reported at the 2023 American Society of Hematology Annual Meeting, Ascentage Pharma has released the updated median 1-year follow-up data of olverembatinib in patients with chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). In the results, olverembatinib showed excellent durable clinical benefits and favorable long-term tolerability in patients who had been treated with multiple TKIs (including those who were resistant to ponatinib and/or asciminib), regardless of whether they harbored the T315I mutation. Dr. Elias Jabbour, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and the Principal Investigator of the study, commented, "The study on olverembatinib demonstrates significant efficacy and a manageable safety profile in patients with heavily pretreated CML and Ph+ ALL, including those with resistance or intolerance to ponatinib and asciminib. These findings indicate that olverembatinib has the potential to be a valuable treatment option for this challenging patient population, warranting further investigation through long-term studies to confirm its clinical benefits." "Updates released at this year's EHA Hybrid Congress, combined with previously reported data, reaffirmed the enormous potential of olverembatinib in patients who are resistant to ponatinib and asciminib," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moving forward, we will expeditiously advance the clinical development of this global best-in-class drug in efforts to bring a new treatment option to patients as soon as possible." Olverembatinib is a global best-in-class drug developed by Ascentage Pharma. As the first China-approved third-generation BCR-ABL1 inhibitor, olverembatinib has been approved for two indications in China, including adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first-and second-generation TKIs. Olverembatinib is jointly commercialized in China by Ascentage Pharma and Innovent Biologics. A global registrational Phase III trial of olverembatinib in treatment-naïve patients with Ph+ ALL is currently ongoing and could potentially lead olverembatinib to become the first TKI approved in China for first-line treatment of Ph+ ALL. The EHA Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year. This year, in addition to the latest data on olverembatinib, Ascentage Pharma also released those of its Bcl-2 inhibitor lisaftoclax (APG-2575) and the EED inhibitor APG-5918. Highlights of those data of olverembatinib presented at EHA 2024 are as follows: Olverembatinib Overcomes Ponatinib and Asciminib Resistance in Patients (Pts) with Heavily Pretreated Chronic Myeloid Leukemia (CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Abstract#: P722 Presentation Type: Poster presentation Topic: Chronic myeloid leukemia – Clinical Date & Time: Friday June 14, 2024, 18:00 - 19:00 CEST Presenting Author: Dr. Elias Jabbour, Department of Leukemia, The University of Texas MD Anderson Cancer Center Highlights: Background: Existing preclinical and clinical data show that olverembatinib, an investigational, novel, potent BCR:: ABL1 TKI, has strong antitumor activity in CML or Ph+ ALL. Introduction: This multicenter, open-label study was designed to assess the safety, efficacy, and pharmacokinetic (PK) profiles of olverembatinib in patients with heavily TKI (including ponatinib and asciminib) pretreated CML or Ph+ ALL. Patient enrollment and methods: As of January 2, 2024, a total of 80 heavily TKI pretreated patients, including 62 patients with CML-CP and 18 patients with advanced Ph+ leukemia (CML-AP, CML-BP, Ph+ ALL), were enrolled. These patients were randomly assigned to receive orally administered olverembatinib at 30, 40, or 50 mg once every other day (QOD) in 28-day cycles. Efficacy results: 1) In patients with CML-CP: 31/51 (60.8%) patients achieved a complete cytogenetic response (CCyR), and 25/59 (42.4%) achieved a major molecular response (MMR). No differences in the response rates of patients with/without the T315I mutation were observed. In patients who failed prior treatment with ponatinib, 15/26 (57.7%) achieved a CCyR (including 10/19 [52.6%] patients with prior resistance to ponatinib and 3/4 [75.0%] with prior intolerance of ponatinib), and 11/30 (36.7%) patients achieved an MMR (including 9/21 [42.9%] patients with prior resistance to ponatinib and 1/6 [16.7%] with prior intolerance of ponatinib). In patients who were asciminib-resistant, 4/8 (50.0%) achieved a CCyR, and 4/12 (33.3%) achieved an MMR. 2) In patients with advanced Ph+ leukemia: 3/14 (21.4%) patients achieved a CCyR, and 3/17 (17.6%) patients achieved an MMR. Safety results: 72 (90.0%) patients experienced treatment emergent adverse events (TEAEs) during their treatment with olverembatinib. Most of the TEAEs were mild to moderate in severity. Common grade≥3 TEAEs included thrombocytopenia (17.5%), neutropenia (12.5%), and increases in blood creatine phosphokinase (12.5%). Serious adverse events occurring in ≥3 (3.8%) patients included atrial fibrillation, COVID-19 infection, febrile neutropenia, and intestinal obstruction. No treatment-related adverse events (TRAE) led to death. Two (2.5%) patients experienced Grade 1 treatment-related arterial occlusive events, one each with angina pectoris and cardiac failure. Conclusions: Olverembatinib was efficacious and well tolerated in patients with heavily TKI pretreated CML-CP and advanced Ph+ leukemias, including ponatinib- or asciminib-resistant/intolerant disease. Combination of Third Generation TKI Olverembatinib and Chemotherapy or Blinatumomab for New Diagnosed Adult Ph+ ALL Patients Abstract#: P427 Presentation Type: Poster presentation Topic: Acute lymphoblastic leukemia – Clinical Date & Time: Friday June 14, 2024, 18:00 - 19:00 CEST Presenting Author: Junjie Chen, Nanfang Hospital, Southern Medical University Highlights: Background: TKIs have improved the long-term outcomes of patients with Ph+ ALL, but resistance to TKIs remains a challenge. Previous reports showed that third-generation TKI ponatinib, combined with chemotherapy, results in a modest rate of complete molecular response (CMR) of 75% in 3 months. Our recent study, a front-line combination of olverembatinib and the PDT-ALL-2016 regimen in Ph+ ALL, had shown a promising outcome, achieving a CMR rate of 84.6% at day 90. Furthermore, the combination of TKI and blinatumomab (BITE) as a chemotherapy-free treatment approach has demonstrated safety and effectiveness. Introduction: This study explored the clinical efficacy of the front-line combination of olverembatinib and chemotherapy (TKI+chemotherapy) or olverembatinib and blinatumomab (TKI+BITE) for the treatment of Ph+ ALL. Patient enrollment and methods: From Jan 2022 to Dec 2023, 31 patients with newly diagnosed Ph+ ALL treated with olverembatinib (40mg once every other day) with pediatric-inspired chemotherapy (n=19; PDT-ALL-2016 protocol) or blinatumomab (n=12; administered for a total of 2 weeks followed by 2 weeks of break) were enrolled. The median age was 40 years old, 15 (48.4%) patients had one comorbid disease, and 8 (25.81%) patients had≥2 comorbid diseases. Efficacy results: With a median follow-up of 16 months, all patients achieved a complete remission (CR) after one cycle of treatment. For the entire cohort, 28 (90.3%) patients achieved a CMR within 3 months. Among them, 16 (84.2%) and 12 (100.0%) patients in the TKI + chemotherapy and TKI + BITE cohorts achieved a CMR within 3 months, respectively. The 1-year overall survival (OS) rate was 93.1% and event-free survival (EFS) rate was 78.4% in the entire cohort. For the TKI + chemotherapy cohort, the 1-year OS rate was 96.2% and the EFS rate was 71.5%. In the TKI + BITE cohort, the 1-year OS rate was 100.0% and the EFS rate was 90.0%. Safety results: Adverse events were observed in 10 (32.3%) patients: 3 patients (9.6%) developed septic shock during treatment, 2 patients (6.4%) experienced mild pancreatitis, 2 patients (6.4%) experienced Pneumocystis jiroveci pneumonia, 2 patients (6.4%) experienced grade 2 cytokine release syndrome (CRS), and 1 patient (3.2%) developed pulmonary embolism. Conclusions: This study showed the combination of olverembatinib and chemotherapy or blinatumomab for treating adult patients with Ph+ ALL. Among the 31 patients enrolled, a notable rate of 1-year survival and CMR was observed, which holds promise for improved long-term survival. Both the TKI + chemotherapy and TKI + BITE cohorts showed good clinical outcomes, although the TKI + BITE cohort exhibited better survival than the TKI + chemotherapy cohort. It is important to note that, although 74.19% of enrolled patients had at least one comorbid disease and the median age was 40 years, the safety profile was acceptable. Patient Reported Outcomes in Adults with TKI-Resistant Chronic Myeloid Leukemia Receiving Olverembatinib-Therapy Abstract#: P1862 Presentation Type: e-Poster presentation Topic: Chronic myeloid leukemia – Clinical Date & Time: 14, 2024, 18:00 - 19:00 CEST Presenting Author: Lu Yu, Peking University People's Hospital Highlights: Background: Third-generation (3G) TKIs have improved the outcomes of patients with TKI-resistant CML. However, there are very limited data on patient reported outcomes in adults receiving 3G TKIs such as olverembatinib. Introduction: The aim of this study was to assess health-related quality of life (HRQoL), anxiety and depression symptoms and identify variables associated with them in patients with TKI-resistant CML receiving olverembatinib-therapy. Patient enrollment and methods: Subjects with TKI-resistance receiving olverembatinib in the multicenter study were invited to complete the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) questionnaires at baseline and regularly during the study treatment. The time trends of the patient reported outcomes were estimated by a linear model using the generalized estimating equation based on the independent working correlation matrix. The generalized estimating equation model was utilized to assess the impact of patients' characteristics at baseline and treatment response during olverembatinib therapy on HRQoL, SAS, and SDS. A total of 159 patients in CP or AP CML were included in this study. Median (range) age was 42 (20-74) years. 104 (65%) patients were male. Interval from diagnosis of CML to initiation of olverembatinib therapy was 5 (0.3-23) years. 77 (48%) patients received olverembatinib therapy within 5 years from the diagnosis of CML. All patients completed the QLQ-C30 questionnaire; and 115 completed the SAS and SDS questionnaires. Survey results: Assessed by the EORTC QLQ-C30 questionnaire, the top 3 severe symptom burdens at baseline were financial difficulties, fatigue, and insomnia. Eight scale items including global health, physical functioning, emotional functioning, fatigue, pain, dyspnea, diarrhea and financial difficulties improved significantly during olverembatinib therapy. No scale deteriorated significantly. In multivariate analysis, age < 40 years was associated with better improvement of social functioning (p = 0.021); CP (vs. AP), better improvement of dyspnea (p = 0.028) and diarrhea (p = 0.042); achieving MMR, better improvement of global health (p = 0.005), nausea and vomiting (p = 0.009), and diarrhea (p = 0.001). At baseline, 96 (84%) patients were normal according to the SAS score; and 19 (16%) had mild or moderate anxiety symptoms. 64 (56%) patients were normal according to the SDS score; 37 (32%) had mild depression symptoms; and 14 (12%), moderate or severe depression symptoms. SAS score was decreased significantly during olverembatinib therapy over time (p < 0.001) while the SDS score did not change significantly. At 36 months on olverembatinib therapy, 78 (95%) and 48 (59%) patients had no anxiety and depression symptoms assessed by SAS and SDS questionnaires, respectively. There was no variable identified that impacted the change of SAS score during olverembatinib therapy. Conclusions: HRQoL and anxiety symptoms significantly improved over time during olverembatinib therapy in patients with TKI-resistant CML. Younger age, CP than AP, and achieving MMR on olverembatinib therapy were associated with better improvements of HRQoL. *Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland. About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma