ASCO 2022 | The First Dataset of Olverembatinib (HQP1351) in Patients with GIST Demonstrates Therapeutic Potential with a Clinical Benefit Rate of 83.3%

SUZHOU, China, and ROCKVILLE, Md., June 7, 2022 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, today announced that it has released the latest results from a Phase Ib/II study of the third-generation tyrosine kinase inhibitor (TKI) olverembatinib (HQP1351) in patients with metastatic gastrointestinal stromal tumor (GIST) who were resistant to or failed prior TKI treatment, in a Poster Discussion session at the 58^th American Society of Clinical Oncology (ASCO) Annual Meeting.

Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the first dataset of olverembatinib in patients with GIST demonstrating a clinical benefit rate (CBR) of 83.3% in the subgroup with TKI-resistant succinate dehydrogenase- (SDH-) deficient GIST.

Although the introduction of TKIs has transformed the management of GIST, TKI-resistant, locally advanced/metastatic GIST remains a major clinical challenge, particularly for patients with SDH-deficient GIST, which is not sensitive to existing TKIs and lacks standard-of-care treatment options.

Olverembatinib is a novel drug developed by Ascentage Pharma and recently received approval in China for the treatment of adult patients with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation, making olverembatinib the first and only approved third-generation BCR-ABL inhibitor in China. While being clinically developed and applied for the treatment of hematologic malignancies, olverembatinib is also being investigated in preclinical and clinical studies for the treatment of GIST, and has already demonstrated promising antitumor activity in multiple preclinical models of GIST.

Prof. Baibo Qiu of Sun Yat-sen University Cancer Center who is the principal investigator of this study, said, "Olverembatinib is a novel third-generation TKI with potent inhibitory activity against a range of kinases, including ABL, KIT, PDGFR, FGFR, b-RAF, DDR1, and FLT3, and has shown antitumor activity in multiple preclinical models of GIST. In this Phase Ib/II clinical study being conducted in China, olverembatinib has demonstrated preliminary efficacy in patients with TKI-resistant GIST, especially in the SDH-deficient subgroup. These data signal olverembatinib's potential as a treatment option for patients with SDH-deficient GIST who currently lack standard of care treatment and suggest it could bring a major breakthrough to this therapeutic area."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "In the past few years, olverembatinib has amassed a wealth of data demonstrating its therapeutic utility in a number of hematologic malignancies such as CML. These clinical data presented at this year's ASCO meeting show that olverembatinib also has clinical potential for the treatment of GIST, thus suggesting a wide therapeutic window for the drug candidate as a multi-kinase inhibitor. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma's drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on olverembatinib are as follows:

Promising antitumor activity of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).

Abstract: #11513

• This is an open-label, multicenter Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of olverembatinib in Chinese patients with locally advanced or metastatic GIST whose disease was resistant or failed to respond to imatinib or other TKIs.
  
  
• As of January 30, 2022, 39 patients had been enrolled. Olverembatinib was administered orally once every other day (QOD) in 28-day repeated cycles. After 3 patients were treated with 20 mg, other patients were randomly allocated in a 1:1:1 ratio to 30, 40, and 50 mg regimens.
  
  
• Efficacy Results:
  
• In the 8 patients with KIT wild-type GIST, 6 were confirmed as SDH-deficient: 2 had partial responses (PRs), 1 patient's tumor shrunk by 35.9% and lasted for 16 cycles, and another patient's tumor shrunk by 54.2% at the first evaluation. 4 patients had stable disease (SD) as the best response for 2, 6, 14, and 36 cycles, resulting in a CBR of 83.3% (complete response [CR]+PR+SD ≥ 4 cycles).
• Among 31 patients who had KIT or PDGFRA mutations, 13 had stable disease for at least 2 cycles as the best response, 8 withdrew early, and 10 had progressive disease before Cycle 3.
  
  
• A total of 36 (92.3%) patients experienced treatment-emergent adverse events, most of which were mild or moderate. Common treatment-related adverse events (≥ 20%) included increased leukocyte (59.0%) and neutrophil (46.2%) counts, anemia (20.5%), constipation or asthenia (35.9% each), hyperuricemia (25.6%), hypoalbuminemia (23.1%), and elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (20.5% each).
  
  
• Conclusions: olverembatinib was well tolerated and showed antitumor activity in patients with TKI-resistant SDH-deficient GIST. These promising findings warrant further investigation.

Appendix: A list of Ascentage Pharma's abstracts selected by this year's ASCO Annual Meeting

About Olverembatinib (HQP1351)

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing program, the orally active, third-generation BCR-ABL inhibitor olverembatinib is the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation. Meanwhile, olverembatinib is being investigated for the treatment of gastrointestinal stromal tumor (GIST) in China.

The clinical results of olverembatinib in hematologic malignancies have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for four consecutive years since 2018, and was nominated for "Best of ASH" in 2019. Olverembatinib has already entered a Phase Ib study in the US and has been granted 3 Orphan Drug Designations (ODDs) and 1 Fast Track Designation (FTD) from the FDA, and 1 Orphan Designation by the EU.

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

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of eight clinical drug candidates, including novel, highly potent Bcl-2, and

dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials in the US, Australia, Europe, and China. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML), was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and is already approved for the indication. In addition, olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EU. To date, Ascentage Pharma has obtained a total of 15 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) designations from the FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects, including 5 National Major New Drug Discovery and Manufacturing projects, 1 New Drug Incubator status, 4 Innovative Drug Programs, and 1 Major Project for the Prevention and Treatment of Infectious Diseases.

Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, Merck, AstraZeneca, and Pfizer. The company has built a talented team with global experience in discovering, developing, launching, and commercializing innovative drugs and is setting up world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

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