Ascentage Pharma and Innovent Announce the China NMPA Accepted and Granted Priority Review Designation to a New Drug Application for Olverembatinib for the Treatment of Drug-Resistant CML

SUZHOU, China, ROCKVILLE, Md. and SAN FRANCISCO, July 19, 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, and Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, today announce that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has accepted and granted Priority Review designation^[1] (in a CDE's public notice ended on July 18, 2022) to a New Drug Application (NDA) that will support the full approval of olverembatinib in patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant and/or intolerant of first- and second-generation tyrosine kinase inhibitors (TKIs). Following the conditional NDA approval in November 2021, the acceptance for the latest application marks another milestone and will potentially bring olverembatinib to benefit a broader population of patients with CML. Ascentage Pharma and Innovent are mutually committed to the commercialization of olverembatinib in China market.

In November 2021, the NMPA granted a conditional approval to olverembatinib for the treatment of adult patients with TKI-resistant CML-CP or CML-AP harboring the T315I mutation as confirmed by a validated diagnostic test, thus filling an urgent treatment gap that has long hindered the clinical outcome in Chinese patients with TKI-resistant CML harboring the T315I mutation.

The acceptance and Priority Review designation for this application are based on the results from an open-label, randomized, controlled, confirmatory Phase II pivotal study (study code: HQP1351CC203) which previously served as the basis for a Breakthrough Therapy designation to olverembatinib by the CDE in March 2021. The study is designed to evaluate the efficacy and safety of olverembatinib in patients with CML-CP who are resistant and/or intolerant to first- and second-generation TKIs, with the event-free survival (EFS) as its primary endpoint. A total of 144 patients were enrolled and randomized to either receive olverembatinib or the control group to receive the current best available treatment (BAT). Results show that olverembatinib significantly improved the EFS compared to the control group and has met the pre-specified superiority criteria. Detailed results from this study will be released at an upcoming academic conference.

CML is a hematologic malignancy of the white blood cells. The introduction of BCR-ABL TKIs has significantly improved the clinical practice and management of CML. However, acquired resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance and there is an urgent unmet medical need for a safe and effective treatment. Olverembatinib is a potentially global best-in-class drug that developed by Ascentage Pharma and supported by the National Major New Drug Discovery and Manufacturing Program in China. As the first and only third-generation BCR-ABL inhibitor approved for the treatment of drug-resistant CML in China, olverembatinib is able to effectively target a spectrum of BCR-ABL mutants, including T315I.

The leading principal investigator of olverembatinib in China, Prof. Xiaojun Huang, MD, Director of the Institute of Hematology, Peking University, Director of the Hematology Department at Peking University People's Hospital, commented: "The approval for olverembatinib last year has brought a breakthrough therapy for patients with drug-resistant CML harboring the T315I mutation. Meanwhile, many patients who are resistant to first- and second-generation TKIs still lack effective treatment and drug resistance to TKIs and this remains a major clinical challenge in the treatment of CML. In recent years, results from multiple clinical studies have validated olverembatinib's therapeutic efficacy in CML patients. We hope that the second Priority Review designation granted to olverembatinib will allow more patients with CML to soon benefit from this novel drug."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "As an innovative biopharmaceutical company dedicated to addressing the unmet medical needs of patients in China and around the world, Ascentage Pharma is forging ahead with its clinical development programs to allow more patients to benefit from our innovative drugs. Having this application for olverembatinib accepted and granted the Priority Review designation by the CDE highlights the authority's commitment to filling the treatment gap in patients with drug-resistant CML and its strong recognition of olverembatinib's therapeutic efficacy. We will work closely with the CDE to bring this innovative therapeutic to more patients as soon as possible."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased about the acceptance and Priority Review designation for the application for olverembatinib, as it will potentially allow a broader population of patients with TKI-resistant CML to benefit from this novel therapeutic. Innovent has established a robust pipeline and franchise in hematology and we are fully committed to bringing forth more 'high-quality biopharmaceutical products that are affordable to ordinary people' and serve the unmet medical needs from Chinese patients as early as possible."

About Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a malignancy caused by the clonal proliferation of hematopoietic stem cell in the bone marrow. Also referred to as chronic myelocytic leukemia, CML is one of the most common subtypes of chronic leukemia, accounting for 15% of all leukemia cases in adults. According to epidemiology data, the onset of CML in Chinese patients happens at a younger age than that in the West; the median age of onset of CML in China is around 45 – 50 years old, while it is 67 years old in the west.

BCR-ABL TKIs have significantly improved the clinical management of CML. However, acquired resistance to TKIs remains a major challenge in the treatment of CML, while BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance.

About Olverembatinib

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

In November 2021, olverembatinib was approved by the NMPA of China for the treatment of adult patients with TKI-resistant CML-CP or CML-AP harboring the T315I mutation as confirmed by a validated diagnostic test. In March 2021, it was granted the Breakthrough Therapy designation by the CDE for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs.

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 four consecutive years, and was nominated for "Best of ASH" in 2019. To date, olverembatinib has been granted one Fast Track designation and three Orphan Drug designations from the US FDA for the treatment of CML, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML); 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 has not been approved for any indication in the U.S.

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.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 32 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) , olverembatinib (BCR-ABL TKI) and Cyramza® (ramucirumab), 3 assets under NMPA NDA review, 3 assets in Phase 3 or pivotal clinical trials, and an additional 19 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT^® (sintilimab injection) is not an approved product in the United States.

BYVASDA^® (bevacizumab biosimilar injection), SULINNO^®, and HALPRYZA^® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT^® (sintilimab injection, Innovent)

BYVASDA^® (bevacizumab biosimilar injection, Innovent)

HALPRYZA^® (rituximab biosimilar injection, Innovent)

SULINNO^® (adalimumab biosimilar injection, Innovent)

Pemazyre^® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre^® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA^® (ramucirumab, Eli Lilly). Cyramza^® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Ascentage Pharma's Forward-Looking Statements

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Innovent's Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

[1] Priority Review Designation accelerates the research and development of innovative drugs that have significant clinical advantages and fills urgent medical needs. According to the Provisions for Drug Registration (SAMR Order No. 27) and Working Procedures for Priority Review and Approval of Drug Marketing Authorization (Interim) (No. 82 of 2020) implemented on July 1, and July 7, 2020, respectively, the regulatory authority will prioritize the review process and evaluation resources for NDAs which helps accelerate the market access of these innovative drugs.

SOURCE Ascentage Pharma