ASH 2021 | Ascentage Pharma Releases Long-Term Clinical Data of Olverembatinib (HQP1351) in Oral Presentation Demonstrating Efficacy and Safety

SUZHOU,China,and ROCKVILLE,Md.,Dec. 14,2021 -- Ascentage Pharma (6855.HK),a global biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today announced that it has released the updated data from three clinical studies of the company's novel drug candidate,olverembatinib,at the 63rd American Society of Hematology (ASH) Annual Meeting. Prof. Qian Jiang,MD,and Prof. Xiaojun Huang,from the Hematology Department of Peking University People's Hospital are the principal investigators of these studies,of which one study was reported by Prof. Jiang in an 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 drug developed by Ascentage Pharma and recently received approval in November 2021 in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation,thus making olverembatinib the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant CML.

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. This year,abstracts from six studies of the company's drug candidates (olverembatinib,lisaftoclax [APG-2575],and pelcitoclax [APG-1252]) were selected for presentations at the ASH Annual Meeting (information on those abstracts about lisaftoclax and pelcitoclax are available in a separate press release published in parallel).

Prof. Qian Jiang commented: "This year,we reported the long-term follow-up data (with a median duration of follow-up of 39 months) that further validated olverembatinib's promising tolerability and potent and durable efficacy,signifying the drug's best-in-class potential. In addition,we reported compelling data from the CC201 and CC202 study in patients with drug-resistant CML harboring the T315I mutation. These two studies have provided clinical evidence that enabled the marketing authorization for olverembatinib that brought about a clinical breakthrough for patients with drug-resistant CML harboring the T315I mutation in China. We hope this novel therapy will soon benefit more patients in need."

"We are very excited about the approval of olverembatinib in China,announced just prior to this year's ASH Annual Meeting. This year marks the fourth year in which the clinical progress of this drug candidate was selected for oral presentation at the ASH Annual Meeting,a strong indication of the international hematology community's recognition of olverembatinib's therapeutic potential," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "It is worth pointing out that this year,we announced olverembatinib's five-year data from 2016 and 2021 which demonstrated efficacy and safety. As China's first and the world's second third-generation BCR-ABL inhibitor,olverembatinib offers a novel therapy with clear efficacy and improved safety to patients with CML. We hope olverembatinib will soon be made available outside China to patients with drug-resistant CML around the world."

These abstracts on olverembatinib presented at the 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

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 September 27,2021 (data cutoff),101 patients with CML-CP (n=86) or CML-AP (n=15) were enrolled and treated with olverembatinib. 71 (70.3%) of those patients were male,at a median age of 40 (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-ABL1T315I genotype. A total of 20 (19.8%) patients had 2 (n=13) or ≥ 3 (n=7) mutations. The median follow-up was 39 (1.2-58.6) months. As of the data cut-off date,77 (77%) of 101 patients continued on the treatment,24 patients discontinued the treatment of which 9 (9%) discontinued due to disease progression,6 (6%) due to adverse events (AEs),4 (4%) due to investigator-confirmed treatment failure,4 (4%) due to withdrawal,and 1 (1%) case of death.

- Of evaluable patients with CML-CP who did not show any response at baseline,100% had complete hematologic responses (CHR),70% had complete cytogenetic responses (CCyR),and 55% had major molecular responses (MMR).

-Among evaluable patients with CML-CP who only harbored the T315I mutation,100% had CHR,90% had MCyR,84% had CCyR,78% had MMR,68% had MMR 4.0,and 58% had MR 4.5.

-Among evaluable patients with CML-CP harboring the T315I and compoundmutations,64% had MCyR,55% had CCyR,58% had MMR,and 25% each for MMR 4.0 and MR 4.5.

-Among evaluable patients with CML-CP harboring other mutations,89% had MCyR,67% had CCyR,64% had MMR,46% had MMR 4.0,and 27% had MR 4.5.

-Among evaluable patients with CML-CP who did not harbor any mutation,9% had MMR,and 5% had MMR 4.0.

- Of evaluable patients with CML-AP who did not show any response at baseline,92% had CHR,and 43% had each CCyR and MMR.

-Among evaluable patients with CML-AP who only harbored the T315I mutation,67% had CHR,60% had each CCyR,MMR,and MMR 4.0,and 40% had MR 4.5.

- Among evaluable patients with CML-AP who harbored the T315I and other compound mutations,MMR 4.0 and MR 4.5.

- Among evaluable patients with CML-AP who harbored other mutations,and none had achieved CCyR or MR.

- Among evaluable patients with CML-AP who did not harbor any mutation,and none had achieved CCyR or MR.

- As of the data cut-off date,the progression-free survival (PFS) rates in patients with CML-CP and CML-AP were 92.7% (84.5%-96.7%) and 56.3% (27.2%-77.6%),and the overall survival (OS) rates were 94.1% (86.4%) and 71.4% (40.6%-88.2%),respectively.

- Olverembatinib demonstrated favorable tolerability and durable antitumor activity in patients with CML,including those with the T315I and compound mutations. Responses were durable and unaffected by baseline BCR-ABL1 mutational status.

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

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

-The most common hematologic TRAEs included thrombocytopenia (77.2),of which 51.5% were grade ≥ 3; leukopenia (23%),of which 21% were grade ≥ 3; and anemia (46%),of which 17% were grade ≥ 3.

All patients who experienced these AEs have recovered after temporary discontinuation,dose adjustments or intervention treatments.

- Conclusions: Olverembatinib was well-tolerated and exhibited durable and potent activity in patients TKI-resistant CML-CP or CML-AP.

Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-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

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-ABL1T315I-mutated) CML-CP and CML-CP,respectively. Olverembatinib was administered at 40 mg orally QOD for 28-day cycles.

- As of the data cutoff on September 30,2021,HQP1351-CC201 had enrolled 41 patients with CML-CP,of whom 32 (78%) completed ≥ 12 cycles. After ≥ 12 treatment cycles in patients without responses at baseline,100% patients experienced CHR; 81 % MCyR; 68% CCyR; and 56% MMR. As of the data cutoff date,the PFS and OS rates in patients with CML-CP were 91.9% (76.9%-97.3%) and 95% (81.5%-98.7%),respectively.

- As of the data cutoff on September 30,HQP1351-CC202 had enrolled 23 patients with CML-CP,of whom 14 (61%) had completed≥ 12 cycles. After ≥ 12 treatment cycles in patients without responses at baseline,74% experienced major hematologic responses (MaHR); 70% CHR; 52% MCyR; 52% CCyR; and 48% MMR. As of the data cutoff date,the PFS and OS rates in patients with CML-AP were 61.8% (37.6%-78.9%) and 69.1% (45.8%-83.9%),respectively.

- 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-ABL1T315I 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

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. Olverembatinib,the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML),was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA),and is already approved for the indication. In addition,the olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA,and an Orphan Designation by the EU. To date,Ascentage Pharma has obtained a total of 12 ODDs from the US FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects,including five National Major New Drug Discovery and Manufacturing projects,one New Drug Incubator status,four Innovative Drug Programs,and one Major Project for the Prevention and Treatment of Infectious Diseases.

Leveraging its robust R&D capabilities,Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology,MD Anderson Cancer Center,Mayo Clinic,Dana-Farber Cancer Institute,MSD,AstraZeneca,and Pfizer. 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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