ABL x PDGFR x c-Kit x Bcr-Abl

SUZHOU, China and ROCKVILLE, Md., April 17, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, today announced that it had released results from three preclinical studies of the company's China-approved novel third-generation BCR-ABL inhibitor olverembatinib (HQP1351), and two key investigational apoptosis-targeted drug candidates of Ascentage Pharma, the Bcl-2 inhibitor lisaftoclax (APG-2575) and the MDM2-p53 inhibitor alrizomadlin (APG-115), in Poster Presentations at the 2023 American Association of Cancer Research Annual Meeting (AACR 2023; Orlando, FL). "The data we presented at this year's AACR Annual Meeting highlight the three drug candidates' potential for clinical development and promising synergistic utilities in new indications," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We will investigate these assets in the clinical setting and hope that these efforts will result in new therapeutic options for patients in need." The details of these posters presented at AACR 2023 are as follows: Combination of olverembatinib (HQP1351) with Bcl-2 inhibitor lisaftoclax (APG-2575) overcomes resistance in gastrointestinal stromal tumors (GISTs) Abstract#: 1631 Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT GISTs are common malignant mesenchymal tumors that occur in the GI tract, with an estimated incidence rate of 1% to 2%. About 75% to 80% of patients with GIST have mutations in the KIT gene, while 5% to 10% have mutations in the platelet-derived growth factor receptor α (PDGFRA) gene. Tyrosine kinase inhibitors (TKIs) offer patients an improved quality of life, but increased pharmacological resistance to TKIs is often observed. Bcl-2 is expressed in >80% of GISTs, and amplification of Bcl-2 and Bcl-xL is a common feature associated with disease progression. One approach to GIST is to concurrently inhibit oncogenic KIT signaling while actively engaging apoptotic pathways. Olverembatinib (HQP1351) is a third-generation TKI that targets BCR-ABL1, KIT and PDGFRA and is currently in development for relapsed or refractory chronic myeloid leukemia and GIST. Lisaftoclax (APG-2575) is a selective Bcl-2 inhibitor under development for hematologic malignancies. The purpose of this study was to evaluate whether combining a Bcl-2 inhibitor, lisaftoclax, with olverembatinib enhances treatment effect on imatinib-resistant GISTs. The results demonstrate that olverembatinib and Bcl-2 inhibitor lisaftoclax have synergistic antitumor effects in imatinib-resistant GIST. Considering that the resistance mechanisms are similar for most TKIs, this novel dual approach may have the potential for treating patients with GISTs whose disease has progressed after treatment with imatinib or other TKIs. Olverembatinib (HQP1351) enhances antitumor effects of immunotherapy in renal cell carcinoma (RCC) Abstract#：5071 Time: Tuesday, April 18, 2023, 1:30 PM-5:00 PM, EDT In solid tumors, resistance to checkpoint inhibitors (CPIs) is frequently observed, partially due to upregulation of vascular endothelial growth factor A (VEGFA) and programmed death-ligand 1 (PD-L1) leading to an immunosuppressive tumor microenvironment and immune escape. Inhibitors against VEGF and the VEGF receptor (VEGFR) foster tumor vessel normalization and immunostimulatory reprogramming, in turn promoting treatment effects of immunotherapies. In recent years, tyrosine kinase inhibitors (TKIs) plus immunotherapy have been approved to treat advanced RCC. Olverembatinib is a third-generation multikinase inhibitor with targets including VEGFR, fibroblast growth factor receptor (FGFR), SRC, BCR-ABL1, c-KIT, and platelet-derived growth factor receptor (PDGFR). The drug is approved in China for the treatment of adult patients with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation, and is currently under clinical development for relapsed or refractory CML and gastrointestinal stromal tumor. The aim of this study was to assess whether olverembatinib combined with immunotherapy can promote inhibitory effects on RCC. The results demonstrate that combining olverembatinib with a CPI confers synergistic antitumor effects in an RCC mouse model by targeting tumor growth, angiogenesis, and immune regulation. This novel combination may provide an alternative approach to enhance treatment effects with CPIs in renal cancers. MDM2 inhibitor alrizomadlin (APG-115) promotes antitumor activity of mitogen-activated protein kinase (MAPK) inhibitors in uveal melanoma Abstract#：1632 Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT Uveal melanoma (UM) is the most common primary intraocular malignancy, yet its molecular pathogenesis is poorly understood. Most UM cases have activating mutations in genes encoding G protein subunits alpha Q or 11, leading to activation of downstream effectors. These include protein kinase C, mitogen-activated protein kinases (MAPK1/3; also termed extracellular signal-regulated kinase 2/1 [ERK2⁄ERK1], respectively), and yes-associated protein, suggesting a rationale for therapeutically targeting these related pathways. Genetic analyses show that TP53 is infrequently mutated in UM, but associated pathways may be functionally inactivated. Ubiquitination-mediated degradation of p53 activates MAPK signaling such that active p53 may promote suppression of MAPK signaling. Alrizomadlin (APG-115) is a small molecule targeting p53/MDM2 that is in clinical development for solid and hematologic cancers. This study evaluated the antitumor effect of alrizomadlin, alone or combined with other targeted therapies, in preclinical models of UM. The results demonstrate the potential utility of combining alrizomadlin with MAPK pathway inhibitors to treat patients with UM. 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 only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials 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, has been granted Priority Review designations and a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). Furthermore, it 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

SUZHOU, China, and ROCKVILLE, Md., June 6, 2022 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, today announced that it has released the latest results from a Phase Ib/II study of the third-generation tyrosine kinase inhibitor (TKI) olverembatinib (HQP1351) in patients with metastatic gastrointestinal stromal tumor (GIST) who were resistant to or failed prior TKI treatment, in a Poster Discussion session at the 58th American Society of Clinical Oncology (ASCO) Annual Meeting. Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the first dataset of olverembatinib in patients with GIST demonstrating a clinical benefit rate (CBR) of 83.3% in the subgroup with TKI-resistant succinate dehydrogenase- (SDH-) deficient GIST. Although the introduction of TKIs has transformed the management of GIST, TKI-resistant, locally advanced/metastatic GIST remains a major clinical challenge, particularly for patients with SDH-deficient GIST, which is not sensitive to existing TKIs and lacks standard-of-care treatment options. Olverembatinib is a novel drug developed by Ascentage Pharma and recently received approval in China for the treatment of adult patients with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation, making olverembatinib the first and only approved third-generation BCR-ABL inhibitor in China. While being clinically developed and applied for the treatment of hematologic malignancies, olverembatinib is also being investigated in preclinical and clinical studies for the treatment of GIST, and has already demonstrated promising antitumor activity in multiple preclinical models of GIST. Prof. Baibo Qiu of Sun Yat-sen University Cancer Center who is the principal investigator of this study, said, "Olverembatinib is a novel third-generation TKI with potent inhibitory activity against a range of kinases, including ABL, KIT, PDGFR, FGFR, b-RAF, DDR1, and FLT3, and has shown antitumor activity in multiple preclinical models of GIST. In this Phase Ib/II clinical study being conducted in China, olverembatinib has demonstrated preliminary efficacy in patients with TKI-resistant GIST, especially in the SDH-deficient subgroup. These data signal olverembatinib's potential as a treatment option for patients with SDH-deficient GIST who currently lack standard of care treatment and suggest it could bring a major breakthrough to this therapeutic area." Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "In the past few years, olverembatinib has amassed a wealth of data demonstrating its therapeutic utility in a number of hematologic malignancies such as CML. These clinical data presented at this year's ASCO meeting show that olverembatinib also has clinical potential for the treatment of GIST, thus suggesting a wide therapeutic window for the drug candidate as a multi-kinase inhibitor. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma's drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need." The highlights of this abstract on olverembatinib are as follows: Promising antitumor activity of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST). Abstract: #11513 This is an open-label, multicenter Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of olverembatinib in Chinese patients with locally advanced or metastatic GIST whose disease was resistant or failed to respond to imatinib or other TKIs. As of January 30, 2022, 39 patients had been enrolled. Olverembatinib was administered orally once every other day (QOD) in 28-day repeated cycles. After 3 patients were treated with 20 mg, other patients were randomly allocated in a 1:1:1 ratio to 30, 40, and 50 mg regimens. Efficacy Results: In the 8 patients with KIT wild-type GIST, 6 were confirmed as SDH-deficient: 2 had partial responses (PRs), 1 patient's tumor shrunk by 35.9% and lasted for 16 cycles, and another patient's tumor shrunk by 54.2% at the first evaluation. 4 patients had stable disease (SD) as the best response for 2, 6, 14, and 36 cycles, resulting in a CBR of 83.3% (complete response [CR]+PR+SD ≥ 4 cycles). Among 31 patients who had KIT or PDGFRA mutations, 13 had stable disease for at least 2 cycles as the best response, 8 withdrew early, and 10 had progressive disease before Cycle 3. A total of 36 (92.3%) patients experienced treatment-emergent adverse events, most of which were mild or moderate. Common treatment-related adverse events (≥ 20%) included increased leukocyte (59.0%) and neutrophil (46.2%) counts, anemia (20.5%), constipation or asthenia (35.9% each), hyperuricemia (25.6%), hypoalbuminemia (23.1%), and elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (20.5% each). Conclusions: olverembatinib was well tolerated and showed antitumor activity in patients with TKI-resistant SDH-deficient GIST. These promising findings warrant further investigation. Appendix: A list of Ascentage Pharma's abstracts selected by this year's ASCO Annual Meeting About Olverembatinib (HQP1351) Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing program, the orally active, third-generation BCR-ABL inhibitor olverembatinib is the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation. Meanwhile, olverembatinib is being investigated for the treatment of gastrointestinal stromal tumor (GIST) in China. The clinical results of olverembatinib in hematologic malignancies have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for four consecutive years since 2018, and was nominated for "Best of ASH" in 2019. Olverembatinib has already entered a Phase Ib study in the US and has been granted 3 Orphan Drug Designations (ODDs) and 1 Fast Track Designation (FTD) from the FDA, and 1 Orphan Designation by the EU. In July 2021, Ascentage Pharma and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in the oncology field in China. 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 eight 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 only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials in the US, Australia, Europe, and China. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML), was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and is already approved for the indication. In addition, olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EU. To date, Ascentage Pharma has obtained a total of 15 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) designations from the FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects, including 5 National Major New Drug Discovery and Manufacturing projects, 1 New Drug Incubator status, 4 Innovative Drug Programs, and 1 Major Project for the Prevention and Treatment of Infectious Diseases. 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, Merck, AstraZeneca, and Pfizer. The company has built a talented team with global experience in discovering, developing, launching, and commercializing innovative drugs and is setting up 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

Los Angeles, USA, Aug. 24, 2021 (GLOBE NEWSWIRE) -- Pulmonary Arterial Hypertension Pipeline Insight Research Report Around 55+ key companies are developing therapies for Pulmonary Arterial Hypertension, among which the drug of Liquidia Technologies is in the advanced stage (Pre Registration) DelveInsight’s “Pulmonary Arterial Hypertension (PAH) Pipeline Insight” report provides comprehensive insights about 55+ companies and 55+ pipeline drugs in the Pulmonary Arterial Hypertension pipeline landscapes. It comprises Pulmonary Arterial Hypertension pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Pulmonary Arterial Hypertension therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Pulmonary Arterial Hypertension pipeline products. Some of the key takeaways from the Pulmonary Arterial Hypertension Pipeline Report Get an overview of pipeline landscape @ Pulmonary Arterial Hypertension Clinical Trials Analysis Pulmonary Arterial Hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure in the arteries of the lungs for no apparent reason. Pulmonary Arterial Hypertension Emerging Drugs Sotatercept is a first-in-class therapeutic fusion protein composed of the extracellular domain of human activin receptor type IIA, fused to the Fc domain of human immunoglobulin G1 (IgG1). The United States Food and Drug Administration (FDA) has granted Orphan Drug designation and Breakthrough Therapy designation to sotatercept for the treatment of PAH; the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to sotatercept for the treatment of PAH. Sotatercept is in Phase III clinical trials for the treatment of PAH. LIQ861 is an investigational, inhaled dry powder formulation of treprostinil designed using the Company’s novel PRINT technology and engineered to enhance deep-lung delivery of treprostinil in PAH patients using a convenient, palm-sized dry powder inhaler. Liquidia resubmits New Drug Application for LIQ861 under the 505(b)(2) regulatory pathway for the treatment of pulmonary arterial hypertension (PAH). Gossamer Bio is developing Seralutinib (GB002) for the treatment of Pulmonary Arterial Hypertension. It is currently in the Phase II stage of development (NCT04456998). It acts as an inhibitor of Platelet-derived growth factor receptors,  CSF1R, c-KIT. Bial is developing Zamicastat for the treatment of Pulmonary Arterial Hypertension. It is currently in the Phase II stage of development (NCT04316143).  It acts as an inhibitor of Dopamine beta-hydroxylase. For further information, refer to the detailed report @ Pulmonary Arterial Hypertension Pipeline Therapeutics Scope of Pulmonary Arterial Hypertension Pipeline Drug Insight ·       Pulmonary Arterial Hypertension Therapies Late-stage (Phase III)  ·       Pulmonary Arterial Hypertension Therapies Mid-stage (Phase II)·       Pulmonary Arterial Hypertension Therapies Early-stage (Phase I) ·       Pulmonary Arterial Hypertension Preclinical stage and Discovery candidates     ·       Discontinued and Inactive candidates ·      Epoprostenol receptor agonists·      Activin inhibitors·      Platelet-derived growth factor receptor antagonists·      Dopamine beta-hydroxylase inhibitors·      Vasoactive intestinal peptide type II receptor agonists·      Angiogenesis inhibitors; Bcr-abl tyrosine kinase inhibitors ·      Cyclin-dependent kinase 4 inhibitors; Cyclin-dependent kinase 6 inhibitors·      Galectin 3 inhibitors ·     Peptides·     Monoclonal antibodies·    Small molecules ·    Proteins·    Gene therapy ·     Parenteral ·      Oral·      Intravenous·      Subcutaneous ·       Monotherapy·       Combination·       Mono/Combination Key Questions regarding Current Pulmonary Arterial Hypertension Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customized pipeline report @ Pulmonary Arterial Hypertension Drugs Pipeline Report Other Reports About DelveInsightDelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. It also provides Healthcare Consulting services comprising credible market analysis that will help accelerate the business growth and overcome challenges with a practical approach.