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., Dec. 10, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that 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 65^th 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.

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