ASH 2021 | Ascentage Pharma to Present Three Studies of Olverembatinib (HQP1351), a Novel Drug Candidate for the Treatment of Drug-Resistant Leukemia, in Abstracts Including One Oral Report at ASH Annual Meeting

SUZHOU, China and ROCKVILLE, MD., Nov. 4, 2021 /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 abstracts on three clinical trials of the company's novel drug candidate, olverembatinib (HQP1351), have been selected for poster presentations and one oral presentation at the 63^rd American Society of Hematology (ASH) Annual Meeting. Presenter, Qian Jiang, MD, and Xiaojun Huang, MD, from the Hematology Department of Peking University People's Hospital are the principal investigators of the study selected for oral presentation. This is the fourth consecutive year in which studies of olverembatinib were selected for oral presentation by the ASH Annual Meeting, demonstrating strong recognition of the drug candidate's promising efficacy and safety by the international hematology community.

Olverembatinib is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma for the treatment of patients with chronic myeloid leukemia (CML) resistant to first- and second-generation TKIs, including those with the T315I mutation, which confers resistance against these agents. The New Drug Application (NDA) submitted by Ascentage Pharma for olverembatinib for the treatment of patients with T315I-mutated CML in chronic-phase (CML-CP) or accelerated-phase (CML-AP) is currently under review in China and has already been granted the Priority Review status. Moreover, olverembatinib was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for the treatment of patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs.

The ASH Annual Meeting is one of the largest gatherings of the international hematology field, bringing together the latest and most cutting-edge research and other scientific and clinical developments in hematology. The 63^rd ASH Annual Meeting will take place on December 11-14, 2021, both virtually and in-person in Atlanta, Georgia, United States. This year, six abstracts on three of Ascentage Pharma's drug candidates (olverembatinib, lisaftoclax [APG-2575], and pelcitoclax [APG-1252]) have been selected by the ASH Annual Meeting for poster or oral presentations (information on those abstracts about lisaftoclax [APG-2575] and pelcitoclax [APG-1252] are available in a separate press release published in parallel).

"These data to be reported at the 2021 ASH Annual Meeting are very encouraging as they demonstrated olverembatinib's promising efficacy and tolerability profiles. This is the fourth year in which the clinical progress of this drug candidate has been selected for oral presentation at the ASH Annual Meeting, a strong indication of the international hematology community's recognition of olverembatinib's potential as a new treatment option for patients with CML," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As China's first and the world's second third-generation BCR-ABL inhibitor, olverembatinib offers patients with CML a potential new treatment with clear efficacy and potentially enhanced safety. We hope that olverembatinib will soon be granted market authorization so that patients with CML in China and around the world can start benefiting from this novel therapeutic."

These abstracts selected for presentations at 2021 ASH Annual Meeting are as follows:

Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML)

• Format: Oral Presentation
• Abstract: 311
• Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Mechanisms of resistance and expanded therapies
• Time: Saturday, December 11, 2021; 5:00 PM EDT
• Highlights

- This Chinese, open-label, multicenter, Phase I trial evaluated the safety and efficacy of olverembatinib in adults with CML-CP or CML-AP. Eligible patients had CML-CP or CML-AP resistant or intolerant to first- and second-generation TKIs. Olverembatinib was orally administered once every other day (QOD) in 28-day cycles and at 11 dose cohorts ranging from 1 to 60 mg. This study reports data on patients with long-term follow-up.

- From October 26, 2016, through February 2, 2021 (data cut-off date), 101 patients with CML-CP (n=86) or CML-AP (n=15) were enrolled and treated with olverembatinib. A total of 71 (70.3%) patients were male, the median age was 40 (range, 20-64) years, and the median (range) interval from diagnosis to initial olverembatinib treatment was 6.0 (0.3-15.2) years. In all, 84 (83.2%) patients received ≥ 2 prior lines of TKI-therapies, and 63 (62.4%) harbored the T315I mutation. At baseline, compound mutations were detected in 11 (10.9%) patients, of whom 7 (63.6%) had the BCR-ABL1^T315I genotype. A total of 20 (19.8%) patients had 2 (n=13) or ≥ 3 (n=7) mutations. The median follow-up was 30.8 (1.2-51.8) months. As of the data cutoff date, 81 (80.2%) of 101 patients continued on the treatment, 18 (17.8%) were treated for > 3 years, and 5 (5%) for > 4 years.

- Of evaluable patients without baseline responses, 97.0% had complete hematologic responses (CHR), 62.1% had complete cytogenetic responses (CCyR), and 51.0% had major molecular responses (MMR).

- Among patients in CML-CP, most evaluable patients with T315I mutations experienced CHR (100%), MCyR (83.7%), or MMR (71.2%).

- Among patients in CML-AP, 80.0% experienced CHR and 54.5% each MCyR or MMR.

At 36 months, the progression-free survival (PFS) rate was 96.3% (89.1%-98.8%) in patients with CML-CP and 71.4% (40.6%‒88.2%) in those with CML-AP.

Treatment responses were durable and unaffected by baseline BCR-ABL1 mutational status. Corresponding values in patients with> 4 years of treatment were 100% (CHR), 80% (CCyR), and 60% (MMR). The mean PFS rate was 100% at 36 or 48 months and not reached (NR-NR) at 60 months.

- Most treatment-related adverse events (TRAEs) were grade 1 or 2.

- The most frequent nonhematologic adverse event (AE) was (mostly grade 1 or 2) skin hyperpigmentation (86.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (5.0%).

- The most common hematologic TRAE was thrombocytopenia in 78 (77.2%) patients, including 52 (51.5% of total population) with grade ≥ 3. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade ≥ 3 in 16 (15.8%) patients.

- Conclusions: In patients with TKI-resistant CML-CP or CML-AP and long-term treatment, olverembatinib was efficacious and well tolerated.

Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1^T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP)

• Format: Poster Presentation
• Abstract: 3598
• Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster III
• Time: Monday, December 13, 2021; 6:00 PM – 8:00 PM EDT
• Highlights:

- HQP1351-CC201 and HQP1351-CC202 are Chinese open, single-arm, multicenter pivotal Phase II trials evaluating the safety and efficacy of olverembatinib in adults with TKI-resistant (BCR-ABL1^T315I-mutated) CML-CP and CML-CP, respectively. Olverembatinib was administered at 40 mg orally QOD for 28-day cycles.

- As of the data cutoff of August 25, 2020, HQP1351-CC201 had enrolled 41 patients with CML-CP, of whom 32 (78%) completed ≥ 12 cycles. The median follow-up was 13 (3.1-16.3) months. After ≥ 12 treatment cycles in patients without responses at baseline, all 31 (100%) experienced CHR (10 other patients had CHR at baseline); 31/41 (75.6%) MCyR; 28/41 (68.3%) CCyR; and 23/41 (56.1%) MMR. At 12 months, the PFS rate was 89.3%, and overall survival (OS) 100%.

- As of the data cutoff of July 27, 2020, HQP1351-CC202 had enrolled 23 patients with CML-CP, of whom 14 (61%) had completed≥ 12 cycles. The median (range) follow-up was 13.5 (1.4-15.2) months. After ≥ 12 treatment cycles in patients without responses at baseline, 17/23 (73.9%) experienced MaHR; 12/23 (52.2%) MCyR; 11/23 (47.8%) CCyR; and 9/23 (39.1%) MMR. At 12 months, the PFS rate was 74.1%, and the OS 91.3%.

- In HQP1351-CC201, the most frequent grade 3-4 TRAE was thrombocytopenia (48.8%), and no treatment-related deaths occurred.

- In HQP1351-CC202, the most frequent grade 3-4 TRAE was thrombocytopenia (56.5%).

- Conclusions: Olverembatinib was efficacious and well tolerated when administered as monotherapy in patients with TKI-resistant CML-CP or CML-AP and the BCR-ABL1^T315I mutation.

Trial in Progress: Phase 1b Bridging Study of the Pharmacokinetic (PK), Safety, and Efficacy of Orally Administered Olverembatinib (HQP1351) in Patients with Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph⁺ ALL)

• Format: Poster Presentation
• Abstract: 2551
• Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
• Time: Sunday, December 12, 2021; 6:00 PM - 8:00 PM EDT
• Highlights:

- This open-label bridging trial in the US is evaluating the PK, efficacy, and safety of olverembatinib administered orally QOD in adults who have CML-CP, CML-AP or blast-phase CML (CML-BP) and Ph⁺ ALL.

- This study is currently recruiting patients, with enrolled individuals being allocated to three dose cohorts: 30, 40, or 50 mg QOD orally. Endpoints of this study include PK, antitumor activity, and safety.

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 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), has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA. A New Drug Application (NDA) for HQP1351 has been submitted and subsequently granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) in China. To date, Ascentage Pharma has obtained a total of 12 ODDs from the US FDA for four 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

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