Global Registrational Phase III Study of Olverembatinib (HQP1351) Cleared by FDA

ROCKVILLE, MD, USA, and SUZHOU, China, February 13, 2024—Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, age-related diseases, and chronic hepatitis B (CHB), announced today that it has received clearance from the US Food and Drug Administration (FDA) to initiate a global registrational Phase III trial of olverembatinib (HQP1351) Read More ›

Olverembatinib Included in Newest Guidelines on Chronic Myeloid Leukemia (CML) Management from the National Comprehensive Cancer Network (NCCN)

SUZHOU, China, and ROCKVILLE, MD, January 16, 2024—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 olverembatinib (R&D Code: HQP1351) has been included in the latest guidelines from the National Comprehensive Cancer Network (NCCN) for the management of  Chronic Myeloid Read More ›

Ascentage Pharma Presented at 42nd Annual J.P. Morgan Healthcare Conference

SUZHOU, China, and ROCKVILLE, MD, January 10, 2024—Ascentage Pharma (6855.HK), a commercial stage global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that Dr. Dajun Yang, the company’s Chairman and CEO, gave a speech at the 42nd Annual J.P. Morgan Healthcare Conference. In the presentation, Read More ›

Ascentage Pharma to Present at 42nd J.P. Morgan Healthcare Conference

SUZHOU, China, and ROCKVILLE, MD, January 1, 2024—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 it will attend the 42nd J.P. Morgan Healthcare Conference, and Dr. Dajun Yang, its Chairman and CEO, will give a presentation on Ascentage Pharma Read More ›

Live from ASH 2023 | Oral Report Featuring Encouraging Data of Olverembatinib Combined with Reduced-Intensity Chemotherapy in Patients with Ph+ ALL Presented at the ASH Annual Meeting

SUZHOU, China, and ROCKVILLE, MD, December 15, 2023—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 Prof. Xiaoyuan Gong of the Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences, has presented the preliminary results from Read More ›

Live from ASH 2023 | Results from Chinese Studies of Olverembatinib Presented in Oral Report at the ASH Annual Meeting for the Sixth Consecutive Year, Including Data Showing Promising Efficacy in Patients with TKI-Resistant and/or Intolerant CML-CP

SUZHOU, China, and ROCKVILLE, MD, December 13, 2023—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 it has released updated data from a randomized, controlled, registrational Phase II study of the company’s novel drug candidate, olverembatinib (R&D code: HQP1351), in Read More ›

Live from ASH 2023 | Ascentage Pharma Releases the First Dataset of Bcl-2 Inhibitor Lisaftoclax in Patients with R/R MM, Demonstrating Encouraging ORR and VGPR

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released the clinical data of lisaftoclax (APG-2575), one of the company’s key drug candidates, combined with various novel therapies in patients with Read More ›

Live from ASH 2023 | Ascentage Pharma Releases Encouraging Long-Term Data of Bcl-2 Inhibitor Lisaftoclax in R/R CLL, Including an ORR of 73.3%

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released the latest efficacy and safety data of lisaftoclax (APG-2575), one of the company’s key drug candidates, in patients with heavily pretreated Read More ›

Live from ASH 2023 | Ascentage Pharma Presents Updated Data from US Study of Olverembatinib, Further Validating Encouraging Efficacy in Patients Resistant to Ponatinib or Asciminib

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released updated data from a US study of the company’s novel drug candidate, olverembatinib (R&D code: HQP1351), in patients with refractory chronic Read More ›

Olverembatinib Approved for New Indications, Allowing More Patients with CML to Benefit from the Drug

SUZHOU, China, and ROCKVILLE, MD, 17 Nov, 2023—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 the China National Medical Products Administration (NMPA) has approved olverembatinib (HQP1351) for the treatment of adult patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant Read More ›

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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

SUZHOU, China, and ROCKVILLE, MD, December 15, 2023—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 Prof. Xiaoyuan Gong of the Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences, has presented the preliminary results from a Phase II study of Ascentage Pharma’s novel drug candidate, olverembatinib, combined with reduced-intensity chemotherapy in treatment-naïve patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), in an Oral Report at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States.

 The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which the clinical results of olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting.

Following the introduction of tyrosine kinase inhibitors (TKIs), the combination of TKIs and intensive chemotherapy has become a widely adopted treatment for patients with Ph+ ALL because it can offer significantly improved prognosis. However, a large number of patients are ineligible for the treatment because of intolerance to intensive chemotherapy. Clinical results featured in this Oral Presentation demonstrated encouraging clinical benefit and favorable tolerability of olverembatinib, a third-generation TKI, when combined with reduced-intensity chemotherapy in patients with Ph+ ALL, with data showing a complete remission/incomplete hematologic recovery (CR/CRi) rate of 100% in patients treated with the olverembatinib combination regimen; a complete molecular response (CMR) rate of 62.2% in patients who received three cycles of the treatment that was free of intensive chemotherapy or immunotherapy; and a favorable tolerability profile. Compared to the existing data on TKI plus intensive chemotherapy combinations, patients on this combination regimen have a lower need for transfusion and a reduced incidence of infections.

Olverembatinib is a global best-in-class novel drug developed by Ascentage Pharma. As the first and only approved third-generation BCR-ABL inhibitor in China, olverembatinib has been approved 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 adult patients with CML-CP resistant and/or intolerant to first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Prof. Xiaoyuan Gong, commented, “The introduction of high-potency TKIs has made it a real possibility to treat patients with Ph+ ALL with reduced-intensity chemotherapy, or even without chemotherapy, while achieving improved efficacy and safety. As a third-generation TKI, olverembatinib has shown impressive therapeutic potential for the treatment of Ph+ ALL and for its role as a key part of chemotherapy-free regimens.”

“In this study, olverembatinib combined with reduced-intensity chemotherapy continued to demonstrate promising clinical benefit in patients with Ph+ ALL, once again indicating the potential superiority of this third-generation TKI over other TKIs and that an era of chemotherapy-free treatment for patients with Ph+ ALL might be on the horizon,” said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. “Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

Olverembatinib Combined with Venetoclax and Reduced-Intensity Chemotherapy for Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Early Results From a Phase II Study

Format: Oral Report

Abstract: #827

Session: 614. Acute Lymphoblastic Leukemia: Therapies, Excluding Transplantation and Cellular Immunotherapies: Optimal Frontline Treatment for ALL

Time: December 11, 2023, Monday; 3:45 PM (Pacific Time) / December 12, 2023, Tuesday; 7:45 AM (Beijing Time)

Highlights:

Background: The combination of olverembatinib (HQP1351), a novel third-generation TKI, with venetoclax generated high response rates in patients with relapsed/refractory (R/R) Ph+ ALL. However, the efficacy and safety of these two agents-based regimens as frontline treatment remains unknown.

Methods: This is a single-arm Phase II study (NCT05594784) that enrolled patients ≥ 14 years (yrs) of age with newly diagnosed Ph+ ALL.

  • In cycle 1, patients were treated with a combination of venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28), olverembatinib (40 mg once every continuously other day [QOD], from day 1-28), vincristine (1.4 mg/m2 [maximum dose 2 mg] on day 1, 8, 15, 22), and prednisone (60 mg/m2 on day 1-14; 40 mg/m2 on day 15-28).
  • In cycle 2-3, oral treatment with venetoclax (400 mg × 7 days), olverembatinib once every other day continuously, and injectable prednisone (60 mg/m2 × 7 days) were administered. Cycles were repeated every 28 days. During cycle 1, the dose of olverembatinib for patients who reached CMR was reduced from 40 mg QOD to 30 mg QOD.
  • The primary endpoint of this study was the rate of CMR at 3 months. CMR was defined as undetectable BCR-ABL1 transcripts by using the RT-PCR method with a sensitivity of 0.001%. Major molecular response (MMR) was defined as more than 3-log reduction of BCR::ABL1 transcripts.

Patients: From August 2022 to July 2023, a total of 45 patients were enrolled. The median age was 42 years (range, 19-74) and males accounted for 48.9%. 31 patients (68.9%) expressed the p190 transcript, and 14 patients (31.1%) expressed the p210 transcript. The median expression level of BCR::ABL1 was 90.3% (range, 25.9%-175.4%).

Efficacy results:

  • All patients have reached CR/CRi. At the end of cycle 1, 53.3% of patients achieved CMR and 28.9% MMR; at the end of cycle 2, 60.0% achieved CMR and 35.6% MMR; at the end of cycle 3, 62.2% achieved CMR and 31.1%
  • As of October 30, 2023, 16 of the 45 patients received autologous hematopoietic stem cell transplantation (Auto-SCT, 1 death), 8 patients received allogeneic hematopoietic stem cell transplantation (Allo-SCT), 5 patients received olverembatinib combined with blinatumomab, and 16 received olverembatinib combined with chemotherapy. 88.9% (40) of patients achieved CMR during treatment.
  • The median (range) duration of follow-up was 8 (3-14) months, and no patient relapsed during follow-up.

Safety results: The combination regimen was well tolerated and safe. Most adverse events were grade 1-2. The demand for transfusion and the incidence of infections significantly decreased compared to the existing data on intensive chemotherapy plus TKI combinations. No patient discontinued olverembatinib or venetoclax because of toxicity.

 Conclusions: The combination of olverembatinib and venetoclax with reduced-intensity chemotherapy is a safe and effective regimen in patients with newly diagnosed Ph+ ALL. The regimen results in high rates of CMR in the absence of intensive chemotherapy or immunotherapy.

*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 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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

SUZHOU, China, and ROCKVILLE, MD, December 13, 2023—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 it has released updated data from a randomized, controlled, registrational Phase II study of the company’s novel drug candidate, olverembatinib (R&D code: HQP1351), in patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or Intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs), in an Oral Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. Prof. Xiaojun Huang and Prof. Qian Jiang, from the hematology department of Peking University People’s Hospital, are the principal investigators of the study.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (including olverembatinib and lisaftoclax) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which study results on olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting.

Data from this Chinese study (HQP1351CC203) of olverembatinib showed that, in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs, the olverembatinib arm achieved statistically significant improvement in event-free survival (EFS) compared to the control arm that was treated with the best available therapy (BAT), thus meeting the primary endpoint of the study with markedly improved prognosis for patients in the olverembatinib arm, compared to those in the control arm. In November 2023, based on results from this study, the China National Medical Products Agency (NMPA) approved olverembatinib for the treatment of adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Prof. Qian Jiang, deputy director of the hematology department of Peking University People’s Hospital and a principal investigator of the study, commented, “In November 2021, olverembatinib was granted its first marketing authorization that ended the lack of effective treatment for patients with T315I mutant CML in China. However, resistance to TKIs remained a major challenge in the treatment of CML. According to existing clinical data, 30%-50% of patients treated with first- or second-generation TKIs develop resistance/intolerance. These patients have a very poor prognosis due to the lack of effective treatments. The updated data from this randomized, controlled, registrational Phase II study showed that olverembatinib significantly improved the EFS for patients with first- and second-generation TKI-resistant and/or intolerant CML while exhibiting potent efficacy and favorable safety. These results supported the recent approval for an additional indication of olverembatinib. We are confident that, through standardized diagnosis and treatment, olverembatinib will benefit the broader population of patients with CML by better treatment responses earlier and further improving the prognosis of patients with TKI-resistant and/or intolerant CML.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “Results from this study supported the recent approval for an additional indication of olverembatinib and the selection for Oral Presentation at the ASH Annual Meeting for the sixth consecutive year, which are encouraging achievements that indicated strong recognition for our work. Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring more safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

Olverembatinib (HQP1351) Demonstrates Efficacy Versus. Best Available Therapy (BAT) in Patients with Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia Chronic-Phase in a Registrational Randomized Phase 2 Study

Format: Oral Report

Abstract: #869

Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Therapeutic Approaches

Time: December 11, 2023, Monday; 3:45 PM (Pacific Time) / December 12, 2023, Tuesday; 7:45 AM (Beijing Time)

Highlights:

Background: Patients with CML resistant and/or intolerant to first- and second-generation TKIs have a high risk of disease progression and poor prognosis. Results from a Phase I study and a registrational Phase II study of olverembatinib (HQP1351-SJ0002, HQP1351CC201/202) have demonstrated favorable safety, potent antitumor activity, as well as potent inhibitory activity against BCR-ABL1WT and T315I mutations. Moreover, olverembatinib also showed significant inhibitory activity against BCR-ABL1 compound mutations.

Methods: The study enrolled patients with CML-CP resistant and/or intolerant to 3 TKIs, including imatinib, dasatinib, and nilotinib, with an ≤ 2 Eastern Cooperative Oncology Group (ECOG) performance score and adequate organ functions. Patients were randomized at a 2:1 ratio to receive olverembatinib (40mg, every other day [QOD]) or BAT (interferon, hydroxyurea, homoharringtonine [HHT], and TKIs [imatinib, dasatinib, and nilotinib] in monotherapy or combinations). The primary endpoint of this study was EFS. After reaching EFS, patients in the BAT arm were allowed to cross-over to the olverembatinib arm for continued treatment.

Patients: As of October 17, 2023, a total of 144 patients were enrolled, of whom 96 patients received olverembatinib and 48 received BAT. In the BAT arm, 22 (47.8%) patients received nilotinib; 16 (34.8%) received dasatinib; 2 (4.3%) received imatinib; 2 (4.3%) received nilotinib combined with hydroxyurea; 2 (4.3%) received dasatinib combined with interferon; 1 (2.2%) received nilotinib combined with interferon; and 1 (2.2%) received interferon combined with hydroxyurea and HHT. The median (range) duration of treatment of the olverembatinib arm and the BAT arm were 21.4 (0.6-44.2) months and 2.9 (0.2-40.5) months, respectively. The median (range) duration of follow-up of the two arms were 30.8 (1.3-46.0) months and 30.4 (0-45.8) months, respectively.

Efficacy results:

  • Clinical data from this study showed, in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs, the olverembatinib arm achieved statistically significant improvement in EFS compared to the BAT arm, thus reaching the primary endpoint. Compared with the BAT control arm, olverembatinib reduced event risk by 60%. The EFS of the olverembatinib arm at 12, 24, and 36 months were 59% (95% CI, 48-68), 47% (95% CI, 36-57), and 47% (95% CI, 36-57), respectively. Among the 48 patients in the BAT arm, 35 (73%) patients were crossed-over to received olverembatinib after reaching the primary endpoint (25/35 patients were crossed-over 3 months prior to this study).
  • The olverembatinib arm showed a significantly higher cumulative response rate than the BAT arm, as well as durable efficacy.

Safety results: In the olverembatinib arm, the median duration of treatment was 21.4 (0.6-44.2) months, and 85.4% of patients experienced grade ≥3 adverse events (AEs). In the BAT control arm, the median duration of treatment was 2.9 (0.2-40.5) months, and 67.4% of patients experienced grade ≥3 AEs. The incidence of grade ≥3 hematologic AEs in the olverembatinib arm declined over time as the treatment went on, and the incidence of grade ≥3 non-hematologic AEs did not increase as the treatment continued. As of October 17, 2023, a total of 98 patients (56 [58.3%] patients in the olverembatinib arm and 42 [87.5%] patients in the BAT control arm) discontinued therapies due to disease progression/treatment failure (13.5% vs 45.8%), AEs (28% vs 31.3%), consent withdrawal (9.4% vs 2.1%), poor compliance (3.1% vs 2.1%), death (1% vs 2.1%), drop-out from follow-up (0%-2.1%), and other reasons (3.1% vs 2.1%).

Conclusions: In patients with TKI-resistant and/or intolerant CML, the olverembatinib arm has achieved significantly improvement in EFS (HR=0.4, 95%CI 0.3,0.5), p<0.001, comparted with the BAT control arm, thus reaching the primary endpoint of the study. In addition, the olverembatinib arm has shown a higher cumulative response rate and longer duration of responses.

* 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 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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

 

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released the clinical data of lisaftoclax (APG-2575), one of the company’s key drug candidates, combined with various novel therapies in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (amyloid light-chain [AL]) amyloidosis, in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. This is the first data readout of lisaftoclax for the treatment of patients with R/R MM.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (lisaftoclax and olverembatinib) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations.

These data signalled the favorable therapeutic potential and tolerability of lisaftoclax combination regimens in patients with hematologic malignancies such as R/R MM. Results showed an overall response rate (ORR) of 66.7% and a very good partial response (VGPR) rate of 28.6% in patients with R/R MM who received lisaftoclax combined with pomalidomide and dexamethasone; and an ORR of 100% and a VGPR rate of 50% in patients with R/R MM who received lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone. Lisaftoclax was well tolerated at doses up to the maximum of 1,200 mg.

Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, “It was the first time to issue efficacy of lisaftoclax in patients with R/R MM, with an outstanding overall response rate. Lisaftoclax was well tolerated even when the combination dose was escalated up to 1200 mg. At the same time, the efficacy of lisaftoclax for patients with AL amyloidosis is also showing up.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “At this year’s ASH Annual Meeting, we presented data of lisaftoclax combinations in patients with malignant plasmocyte diseases such as R/R MM that demonstrated promising ORR, VGPR; and favorable tolerability at doses up to 1,200 mg. These results reaffirmed the global best-in-class potential and unique therapeutic utility of lisaftoclax. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

First Report on the Effects of Lisaftoclax (APG-2575 in Combination with Novel Therapeutic Regimens in Patients with Relapsed or Refractory Multiple Myeloma (R/R MM or Immunoglobulin Light-Chain (Amyloid Light-Chain [AL] Amyloidosis

 Format: Poster Presentation

Abstract: #2016

Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster I

Time: December 9, 2023, Saturday, 5:30 PM – 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time)

Highlights

Background: Lisaftoclax is an investigational, novel, potent, selective Bcl-2 inhibitor under clinical development for treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefits. In a previous study on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other hematologic malignancies, lisaftoclax was shown to require only a short dose ramp-up to mitigate tumor lysis syndrome (TLS) and was associated with a low incidence of adverse events (AEs). This multicenter study was designed to evaluate the safety and efficacy of lisaftoclax combination regimens in patients with R/R MM or R/R AL amyloidosis.

 Methods:

  • This study has three treatment arms that included Arm A: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R MM; Arm B: lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone in patients with R/R MM; and Arm C: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R AL amyloidosis.
  • Lisaftoclax was administered orally once daily (QD) at 5 dose levels (400 mg, 600 mg, 800 mg, 1,000 mg, and 1,200 mg) without ramp-up in 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone 40 mg (20 mg for patients aged >75 years) was administered on Days 1, 8, 15, and 22 of 28-day cycles.

Patients: As of July 3, 2023, a total of 30 patients were enrolled. Among them, 22, 3, and 5 patients were enrolled into Arms A, B, and C, respectively. 66.7% of patients were male, and the median (range) age was 70.5 (24-88) years. All patients were previously exposed to multiple lines of treatment. 18 (60%) patients were triple-class-exposed, 7 (35%) had received pomalidomide and 3 (10%) harbored the t(11;14) chromosomal abnormality.

Efficacy results:

  • In Arm A, 21 patients with R/R MM were efficacy evaluable, including 6 (28.6%) who have reached VGPRs and 8 (38.1%) who have reached partial responses (PRs), resulting in an ORR (PR + VGPR) of 66.7%.
  • In Arm B, 1 patient with R/R MM achieved PR and another achieved VGPR, resulting in an ORR of 100%.
  • In Arm C, 3 patients with R/R amyloidosis achieved a hematologic VGPR, resulting in an ORR of 60%; 1 patient achieved improvement in organ functions.

Conclusions: Lisaftoclax combination regimens were well tolerated and demonstrated potent antitumor activity (especially VGPRs and PRs) in patients with R/R MM and R/R AL amyloidosis.

* Lisaftoclax (APG-2575) is an investigational drug that has not been approved in any country and region.

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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released the latest efficacy and safety data of lisaftoclax (APG-2575), one of the company’s key drug candidates, in patients with heavily pretreated chronic lymphocytic leukemia (CLL), in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (lisaftoclax and olverembatinib) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations.

These data in patients with R/R CLL reaffirmed the potential clinical benefit and tolerability of lisaftoclax. Results showed an overall response rate (ORR) of 73.3%; a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 24.4%; and a positive correlation between CR/CRi rate and dose levels. In addition, the study observed a low incidence of tumor lysis syndrome (TLS) that is comparable to the results of earlier studies.

Prof. Keshu Zhou, MD, at Henan Cancer Hospital and the presenter of this report, commented, “Our report this year has focused on the efficacy, particularly deep responses including the CR/CRi rate and measurable residual disease (MRD) negativity of Chinese patients with R/R CLL who were treated with lisaftoclax monotherapy. Having been treated with a wide spectrum of doses that ranged from 100 to 800 mg, these patients showed a CR/CRi rate of 24.4%. While in long-term follow-up, the study observed a 30-month overall survival (OS) rate of 86.3% that indicated the drug’s potential in bringing long-term survival benefit to patients with CLL.”

Prof. Jianyong Li, MD, at Jiangsu Province Hospital and the principal investigator of the study, noted, “In a series of Phase Ib/II studies carried out in China and overseas, lisaftoclax has demonstrated its strong therapeutic potential, while results from long-term follow-up reaffirmed the high response rate, long-term safety, and long-term survival benefit of lisaftoclax. In the field of CLL, lisaftoclax has made considerable strides towards confirmatory trials. We hope that this Bcl-2 inhibitor will soon have these results validated in larger samples of the broad CLL population and eventually be approved for wide clinical adoption.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “Lisaftoclax is the first Bcl-2 inhibitor that demonstrated clear efficacy in China and the second globally. At this year’s ASH Annual Meeting, we presented encouraging data of lisaftoclax in patients with CLL that reaffirmed the drug’s promising clinical benefit, favorable tolerability, and strong global best-in-class potential. Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

Updated Efficacy and Safety Results of Lisaftoclax (APG-2575) in Patients (pts) with Heavily Pretreated Chronic Lymphocytic Leukemia (CLL): Pooled Analyses of Two Clinical Trials

Format: Poster Presentation

Abstract: #1900

Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

Time: Saturday, December 9, 2023; 5:30 PM – 7:30 PM (Pacific Time) / Sunday, December 10, 2023; 9:30 AM – 11:30 AM (Beijing Time)

Highlights:

Background: Lisaftoclax is a novel selective Bcl-2 inhibitor that has demonstrated antileukemic activity and favorable tolerability in patients with CLL. This poster reported updated data from 14-month follow-up in two Phase Ib/II studies (APG-2575-CN001 [NCT03913949] and APG-2575-CC101 [NCT04494503]) of lisaftoclax in patients with CLL.

Methods: In the 2 studies, lisaftoclax was administered orally once daily in 28-day cycles, in 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg dose cohorts. Under close monitoring for prevention and early detection of TLS, patients were treated (with a daily dose ramp-up schedule) until disease progression, intolerable toxicity, or death.

Patients: As of April 27, 2023, a total of 47 patients with CLL were enrolled. The median (range) age was 58 (34-80) years. At enrollment, 53.2% of patients were in Rai stage III/IV, and 48.9% of patients were in Binet stage C. 44.7% of patients had received ≥3 lines of treatment; 66.0% of patients had received ≥2 lines of treatment; 23.4% of patients were previously treated with Bruton tyrosine kinase inhibitors (BTKis); and 55.3% were previously treated with a CD20 monoclonal antibody.

Efficacy results: In patients with CLL, the ORR and CR/CRi were 73.3% (33/45) and 24.4% (11/45), respectively, and the CR/CRi rate exhibited an upward trend with increases in dose levels. Among patients who were tested for MRD in peripheral blood, 38.9% (7/18) achieved the MRD-negative status. Among patients who were tested for MRD in bone marrow, 66.7% (4/6) were MRD-negative. The median time (range) to the first response was 2.07 (1.94-3.94) months, the median progression-free survival (PFS) was 18.53 (95% CI, 9.13-24.05) months, and the rate of OS at month 30 was 86.3% (95% CI, 66.1%-94.9%).

Safety results: In total, 76.6% (36) of patients experienced grade ≥3 adverse events (AEs); 27.7% (13) experienced serious AEs (SAEs). The incidence of treatment-emergent AEs (TEAEs) was not dose-dependent. Treatment-related adverse events (TRAEs) were observed in 95.7% (45) of patients, of whom 68.1% (32) experienced grade ≥3 TRAEs and 14.9% (7) experienced SAEs. One case of TLS was reported. 68.1% (32) of patients discontinued the study because of disease progression (51.1%), patient withdrawal (6.4%), AEs (2.1%), investigator’s decision (2.1%), poor compliance (2.1%), protocol deviation (2.1%), and other reasons (2.1%).

 Conclusions: Lisaftoclax demonstrated favorable tolerability and significant efficacy in patients with R/R CLL, and the CR/CRi rate was positively correlated with escalating dose levels.

* Lisaftoclax (APG-2575) is an investigational drug that has not been approved in any country and region.

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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

SUZHOU, China, and ROCKVILLE, MD, December 11, 2023—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 it has released updated data from a US study of the company’s novel drug candidate, olverembatinib (R&D code: HQP1351), in patients with refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that representleading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which clinical results on olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting.

After releasing preliminary results of the US study in an Oral Report at last year’s ASH Annual Meeting, this year Ascentage Pharma presented updated data from a larger patient sample that reaffirmed the favorable clinical benefit and tolerability of olverembatinib, as a monotherapy and in combinations, in heavily pretreated patients with CML and Ph+ ALL, particularly those who have failed prior treatment with the third-generation TKI ponatinib or the allosteric STAMP inhibitor asciminib.

Prof. Elias Jabbour, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and the Principal Investigator of the study, commented, “Once again, the follow-up data of study HQP1351CU101 showed olverembatinib’ s excellent treatment response, especially in patients who were resistant to ponatinib or asciminib. Olverembatinib will provide an effective new treatment option for CML and Ph+ ALL patients.”

“Building on the encouraging results presented at last year’s ASH Annual Meeting, the data released this year validated olverembatinib’s promising therapeutic potential in patients resistant to ponatinib or asciminib. These encouraging results once again underscored the potential of this China-developed global best-in-class drug in addressing the unmet needs of patients with CML and Ph+ ALL worldwide,” said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. “Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring more safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

Update of Olverembatinib (HQP1351) Overcoming Ponatinib and/or Asciminib Resistance in Patients (Pts) with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

 Format: Poster Presentation

Abstract: #1798

Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I

Time: December 9, 2023, Saturday, 5:30 PM – 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time)

Highlights:

Background: Patients with CML who failed on first- and second-generation tyrosine kinase inhibitors (TKIs) have a poor prognosis. Olverembatinib, a novel third-generation TKI, has shown strong antitumor activity in patients with CML and Ph+ ALL. This presentation reports on the safety, efficacy, and pharmacokinetics (PK) of olverembatinib in patients with CML and Ph+ ALL outside of China, particularly in patients previously treated with third-generation TKI ponatinib and/or allosteric STAMP inhibitor asciminib.

Methods: Olverembatinib was administered orally once every other day (QOD). In the monotherapy cohort, patients were enrolled after treatment failures on at least 2 prior TKIs (no limit on the number of prior TKIs for patients harboring the T315I mutation) and randomized to receive olverembatinib QOD at 30, 40, or 50 mg, in 28-day cycles. In the combination cohort, patients with Ph+ B-cell precursor ALL (BCP ALL) or lymphoid CML-BP (CML-LBP) resistant to at least 1 second-generation TKI were enrolled and administered olverembatinib (30 or 40 mg) QOD in combination with CD19/CD3 bispecific antibody (bispecific T-cell engager) blinatumomab.

Patients: As of June 30, 2023, 76 patients were enrolled, including 57 with CML in chronic phase (CML-CP) and 19 with advanced Ph+ leukemia (CML-AP, CML-LBP, Ph+ ALL). The median (range) age was 54.5 (21-80) years, and 56.6% of patients were male.

  • 11 (14.5%), 23 (30.3%), and 39 (51.3%) patients had received 2, 3, and ≥4 TKIs, respectively.
  • A total of 40 (52.6%) patients were previously treated with ponatinib, of whom 67.5% were resistant, 25.0% were intolerant to the drug, and 7.5% of patients failed for other reasons.
  • A total of 21 (27.6%) patients were previously treated with asciminib, of whom 71.4% were resistant and 19.1% were intolerant to the agent, and 9.5% failed for other reasons.
  • At baseline, 31.6% of patients had T315I mutations, and 38.2% had hypertension.
  • The median (range) duration of treatment was 24.1 (0-134) weeks. PK analysis showed that patients worldwide had a PK profile similar to historical data on Chinese patients.

Efficacy results:

  • Among 50 efficacy-evaluable patients with CML-CP, 56.8% (25/44) achieved a complete cytogenetic response (CCyR), and 42.9% (21/49) achieved a major molecular response (MMR). In patients with CML-CP harboring the T315I mutation, CCyR and MMR rates were 60.0% (9/15) and 43.8% (7/16), respectively; In patients without the T315I mutation, CCyR and MMR rates were 55.2% (16/29) and 42.4% (14/33), respectively; In patients who were ponatinib-resistant, CCyR and MMR rates were 53.3% (8/15) and 37.5% (6/16), respectively; In patients who were asciminib-resistant, CCyR and MMR rates were 42.9% (3/7) and 37.5% (3/8), respectively.
  • Among the 13 efficacy-evaluable patients with advanced Ph+ leukemia, 23.1% (3/13) achieved MMR, of whom 1 patient harbored the T315I mutation and 2 were T315I mutation negative and resistant to ponatinib.
  • In the combination cohort, 2 patients with Ph+ BCP ALL received olverembatinib 30 mg QOD in combination with blinatumomab. Both patients achieved CCyR and 1 achieved negative minimal residual disease (MRD) status after 1 treatment cycle.

Safety results: A total of 12 patients with CML-CP and 7 with advanced Ph+ leukemia discontinued treatment for reasons including adverse events (AEs n=4), disease progression (n=7), and other reasons (n=8). A total of 54 (83.1%) patients experienced treatment-related AEs (TRAEs) of any grade after receiving olverembatinib. Grade ≥3 TRAEs occurring in ≥3 patients included thrombocytopenia (17.0%), neutropenia (13.8%), elevated blood creatine phosphokinase (13.8%), leukopenia (7.7%), anemia (4.6%), and elevated lipase (4.6%). 10 (15.4%) patients experienced treatment-related serious AEs (SAEs).

Conclusions: Olverembatinib monotherapy or combined with blinatumomab was efficacious and well tolerated in heavily pretreated patients with CML or Ph+ ALL and was potent in patients who were resistant or intolerant to ponatinib and/or asciminib, regardless of the T315I mutation status. Olverembatinib may provide an effective treatment option for patients with CML or Ph+ ALL who have failed on two or more TKIs.

* 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 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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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.

SUZHOU, China, and ROCKVILLE, MD, 17 Nov, 2023—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 the China National Medical Products Administration (NMPA) has approved olverembatinib (HQP1351) for the treatment of adult patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant of first-and second-generation tyrosine kinase inhibitors (TKIs). This approval, marking yet another major milestone for olverembatinib following its first regulatory approval in 2021 and the subsequent inclusion into the China 2022 National Reimbursement Drug List (NRDL), which will benefit a broader population of patients with CML in China.

This approval for olverembatinib is based on the results from an open-label, national multicenter, randomized-controlled, registrational pivotal Phase II study (HQP1351CC203) that evaluated the efficacy and safety of olverembatinib in patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. Patients were randomized to either receive olverembatinib or into the control group to receive the current best available treatment (BAT). Results from the study show that compared to patients who were treated with the BAT in the control group, those received olverembatinib achieved statistically significant improvement in the primary endpoint of event-free survival (EFS),meeting the primary endpoint of the study. In March 2021, the Center of Drug Evaluation (CDE) of the NMPA granted olverembatinib a Breakthrough Therapy Designation (BTD) to olverembatinib; and in July 2022, the New Drug Application (NDA) for olverembatinib in this indication was accepted and granted a Priority Review Designation by the CDE.

CML is a hematologic malignancy of the white blood cells. The introduction of BCR-ABL TKIs has significantly improved the management of CML. However, 20%-40% of patients fail to achieve desired treatment outcome due to resistance or intolerance to TKIs1-3, thus leading to disease progression or even death. At present, resistance to TKIs is posing a major challenge to the management of CML globally and patients are in desperate need of a new generation of drugs that are safe and efficacious.

Olverembatinib is a global best-in-class novel drug developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China. As the first and only China-approved third-generation BCR-ABL inhibitor, olverembatinib can effectively target BCR-ABL and a spectrum of BCR-ABL mutants, including the T315I mutation. In November 2021, olverembatinib was approved in China for the treatment of adult patients with TKI-resistant CML-CP or accelerated-phase CML (CML-AP) harboring the T315I mutation. In January 2023, olverembatinib has been officially included into the China National Reimbursement Drug List, further enhancing the affordability and accessibility of the drug. Ascentage Pharma and Innovent are mutually committed to the commercialization of olverembatinib in the China market.

Prof. Xiaojun Huang, MD, Director of the Institute of Hematology, Peking University, Director of the Hematology Department at Peking University People’s Hospital, and a principal investigator of olverembatinib in China, commented, “The first approval for olverembatinib has brought about a long-awaited breakthrough to the treatment of T315I mutant CML in China. Meanwhile, patients who are resistant to or intolerant of first- and second-generation TKIs still lack effective treatment options. Olverembatinib’s efficacy and safety for the treatment of drug-resistant CML has been validated repeatedly in a number of studies and this expansion of the drug’s indications is widely anticipated by patients and clinicians. I am pleased that olverembatinib is now approved for the treatment of patients with TKI-resistant CML-CP as it will help more patients to achieve deeper responses faster, offer a better prognosis to patients, and improve patients’ overall survival. Furthermore, this approval for olverembatinib will also bring the management of CML to the next level in China.”

Prof. Qian Jiang, MD, Deputy Director of the Hematology Department at Peking University People’s Hospital, and another principal investigator of olverembatinib in China, noted, “A sizeable portion of patients with CML eventually experience disease progression due to their resistance to or intolerance of first- or second-generation TKIs. Even after being switched to the second or third TKIs, many of those patients would develop new mutations or complications, thus fail to achieve desired responses. Clinically, there is currently an enormous need for a new generation of drugs that are safe and effective. Existing data show that the third-generation TKI olverembatinib has potent antitumor activity, durable efficacy, and a manageable safety profile in patients with CML who harbour complex mechanisms of drug resistance following multiple lines of failed treatment. I am encouraged by this expansion of olverembatinib’s indications as it will bring renewed hope to broader population of patients with drug-resistant CML.”

Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma, said, “This indication expansion marks another major milestone for olverembatinib which would not have been possible without the strong support from our regulators and government agencies, as well as the trust and efforts from the investigators and patients who took part in the clinical studies of olverembatinib. We are very encouraged that a broader population of patients in China can now benefit from olverembatinib, a China-developed high-quality global best-in-class novel therapeutic, and to see our persistent innovation bringing meaningful improvement to patients’ lives. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will continue to investigate olverembatinib in additional indications and accelerate our clinical development programs to benefit more patients.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, “We are very excited by this indication expansion for olverembatinib, the first and only China-approved third-generation BCR-ABL inhibitor and a China-developed global best-in-class novel drug. I would like to thank all branches of the Chinese drug regulator for their recognition of olverembatinib’s safety and efficacy and for clearing the drug’s path to bringing survival benefit to more patients. Encouraged by the latest approval, we are ever more confident in pursuing original innovation with our global R&D strategies and in bringing more China-developed globally advanced novel therapeutics to patients in need.”

References

  1. O’Brien SG, Guilhot F, Larson R, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. Engl J Med. 2003 Mar 13;348(11):994-1004.
  2. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management. Am J Hematol. 2014 May;89(5):547-56.
  3. Larson R, Hochhaus A, Hughes T, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia. 2012 Oct;26(10):2197-203.

 About Olverembatinib (HQP1351)

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the orally active, third-generation tyrosine kinase inhibitor (TKI) olverembatinib is the first and only China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target BCR-ABL and a spectrum of BCR-ABL mutants, including the T315I mutation.

In November 2021, olverembatinib was granted a conditional approval through the Priority Review process by the China National Medical Products Administration (NMPA) for the treatment of adult patients with TKI-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. Subsequently, Olverembatinib was included into the China 2022 National Reimbursement Drug List (NRDL) for the approved indication. In March 2021, olverembatinib was granted a Breakthrough Therapy Designation (BTD) by the Chinese Center for Drug Evaluation (CDE) for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs. In Nov 2023, the New Drug Application (NDA) for this indication was approved by the NMPA through the Priority Review process. In addition, the registrational pivotal Phase III study of olverembatinib for the first-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has already dosed its first patient. In solid tumors, olverembatinib was granted a BTD by the CDE in June 2023 for the treatment of patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had received first-line treatment.

In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. Since 2018, the clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for five consecutive years, and was nominated for “Best of ASH” in 2019. To date, olverembatinib has been granted one Fast Track Designation (FTD) and four Orphan Drug Designations (ODDs) from the US Food and Drug Administration (FDA) for the treatment of CML, ALL, acute myeloid leukemia (AML), and GIST; and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.

In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.

*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 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 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.

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