Ascentage Pharma and Innovent Biologics Announce Approval for China's First Third-Generation BCR-ABL TKI Olverembatinib, Marking a Clinical Breakthrough in the Treatment of Chronic Myeloid Leukemia

SUZHOU, China and ROCKVILLE, Md., Nov. 30, 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, 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 and other major diseases, jointly announce that the novel drug candidate olverembatinib of Guangzhou HealthQuest Pharma Co., Ltd., Inc., a wholly-owned subsidiary of Ascentage Pharma, has been approved by the China National Medical Products Administration (NMPA) 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 as confirmed by a validated diagnostic test (an indication that has not been approved in the US).

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing program, olverembatinib is a potentially best-in-class drug that will be co-commercialized in China market by Innovent and Ascentage Pharma, for the benefit of more patients and their families. As China's first third-generation BCL-ABL TKI developed for the treatment of TKI-resistant CML, this approval fills an important treatment gap in T315I-mutant CML, and marks a major milestone signifying that Ascentage Pharma has successfully entered the commercial-stage.

This approval for olverembatinib is based on the results from two pivotal Phase II studies – the HQP1351CC201 study and the HQP1351CC202 study. These results showed that olverembatinib is efficacious and well-tolerated in patients with CML-CP and CML-AP, and the probability and depth of clinical response is expected to increase with prolonged treatment period.

CML is a hematologic malignancy of the white blood cells. The introduction of 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. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance; T315I, which is the most common drug-resistant mutation, occurs in about 25% of patients with drug-resistant CML. Patients with T315I-mutant CML are resistant to both first- and second-generation BCR-ABL inhibitors, hence presenting an urgent unmet medical need for an effective treatment.

Prof. Xiaojun Huang, MD, Director of the Institute of Hematology, Peking University, Director of the Hematology Department at Peking University People's Hospital, and a principal investigator of olverembatinib in China, commented: "Efficacy and safety data from studies to date have consistently showed that olverembatinib has enormous potential in effectively addressing the unmet medical need in the treatment of chronic myeloid leukemia, and is a drug with true best-in-class potential. The clinical progress with this novel therapeutic has also received widespread interest from the global hematology community over the years. I am excited that olverembatinib is now approved in China, as it finally brings about a breakthrough to the clinical conundrum caused by drug-resistance and a milestone in the treatment of CML. In a broad sense, this approval also signifies that China is rapidly emerging as a world leader in hematology clinical development."

Prof. Qian Jiang, MD, Deputy Director of the Hematology Department at Peking University People's Hospital, and another principal investigator of olverembatinib in China, noted: "First- and second-generation TKIs are ineffective in patients with T315I-mutant CML-CP and CML-AP, and drug-resistant CML has long represented an urgent unmet clinical need. This approval for olverembatinib bears great significance for doctors and patients, as it offers a long-awaited change to the treatment landscape in CML. I am confident that the approval of olverembatinib will bring significant survival benefit and renewed hope to patients with CML."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, President and CEO of Healthquest Pharma commented: "We are grateful to all the regulators and agencies for their understanding of the urgent clinical needs of patients with CML, and their strong support to home-grown pharmaceutical innovation in China. I would also like to thank all the clinical experts for their trust and dedication to the clinical development program of olverembatinib. Last but not least, I would like to express my most heartfelt appreciation for the employees of Ascentage Pharma for their dedication and perseverance that allowed us to overcome the unprecedented challenges posed by the COVID-19 pandemic. This approval for olverembatinib, China's first and the world's second approved third-generation BCR-ABL inhibitor, not only brings hope to Chinese patients with T315I-mutant CML who would otherwise have no effective treatment, it also indicates the drug's potential in addressing a major unmet need in the treatment of CML globally."

Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, said: "This approval for olverembatinib, Ascentage Pharma's first product entering commercialization, marks a very encouraging milestone in our transition from a R&D-driven biotech into a full-fledged biopharmaceutical company with commercialized product. We will fully engage Innovent to expedite the buildout of the commercial infrastructure for olverembatinib. Meanwhile, we are partnering with stakeholders such as genetic testing companies, commercial insurance companies, and online pharmacies, in order to make this China-developed novel therapy accessible to more patients , honoring our commitment to global innovation and the mission of addressing unmet clinical needs in China and around the world. Moving forward, we will continue to explore additional indications of this drug, advance its clinical development overseas, and accelerate the global development of other drug candidates in our pipeline, to further solidify our global presence. "

Dr. Michael Yu, Founder, Chairman and CEO of Innovent Biologics, said: "We are pleased about the NDA approval of olverembatinib in China, which further strengthens Innovent's franchise in oncology and hematology area by adding a new generation anti-cancer therapy to our commercial portfolio. In oncology area, Innovent has a robust pipeline of up to 20 assets, an industry-leading product development team, and a broad channel coverage with a commercial team of nearly 3000 people. We look forward to collaborating with Ascentage Pharma for the co-commercialization of olverembatinib, in order to bring forth this novel drug to solve the unmet medical needs from Chinese TKI-resistant T315I-mutated CML patients as early as possible."

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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^{[1]- [2]}. 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^[3].

BCR-ABL tyrosine kinase inhibitors (TKIs) have significantly improved the clinical 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; T315I, which is the most common drug-resistant mutation, occurs in about 25% of patients with drug-resistant CML. Patients with T315I-mutant CML are resistant to both first- and second-generation BCR-ABL inhibitors, therefore the mutation had long been a clinical obstacle undermining patients' long-term survival.

About Olverembatinib

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.

In October 2020, olverembatinib was granted the Priority Review status by the Center for Drug Evaluation (CDE) in China for the treatment of adult patients resistant to TKIs and with T315I-mutant chronic phase CML (CML-CP) and accelerated phase CML (CML-AP). In March 2021, it was granted the Breakthrough Therapy designation by the CDE. In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. In May 2020, olverembatinib was sequentially granted an Orphan Drug designation and Fast Track designation by the US FDA. In November 2021, olverembatinib was granted an Orphan Designation by the European Union. Furthermore, 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. (Olverembatinib has not been approved for any indication in the US.)

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

Results from the two pivotal Phase II studies

The HQP1351CC201 study in patients with CML-CP

• HQP1351CC201 is an open-label, multicenter, single-arm Phase II designed to evaluate the safety and efficacy of patients with T315I-mutant CML-CP who have received prior treatment with BCR-ABL1 TKIs. The primary endpoint of the study is major cytogenetic response (MCyR).
• As of data cut-off date of August 25, 2020, the median duration of follow-up in patients with CML-CP was 13.0 months (range: 7.2-16.3). Of the 31 patients evaluable for hematologic responses, all 31 (100%) patients achieved a complete hematologic response (CHR); In the 41 patients evaluable for cytogenetic responses, 31 (75.6%) patients achieved a MCyR, including 28 (68.3%) with complete cytogenetic response (CCyR), and 3 (7.3%) with partial cytogenetic response (PCyR); Among the 41 patients evaluable for molecular responses, 23 (56.1%) achieved a major molecular response (MMR). The 12-month progression-free survival (PFS) was 85.7% (95% CI: [63.6%-94.9%]) and the overall survival (OS) was 100% (95% CI: [100.0% -100.0%].

The HQP1351CC202 study in patients with CML-AP

• HQP1351CC202 is an open-label, multicenter, single-arm Phase II designed to evaluate the safety and efficacy of patients with T315I-mutant CML-AP and resistance to TKIs developed on prior treatment with BCR-ABL1 TKIs. The primary endpoint of the study is major hematologic response (MaHR).
• As of data cut-off date of July 27, 2020, the median duration of follow-up in patients with CML-AP was 14.3 months (range: 6.6-15.2). Of the 17 patients evaluable for hematologic responses, 12 (70.6%) patients achieved a major hematologic response (MaHR), including 11 (64.7%) with CHR and 1 (5.9%) with no evidence of leukemia (NEL); Among the 17 evaluable patients, 8 (47.1%) achieved a MCyR, all of whom achieved (47.1%) a CCyR, and another 7 (41.2%) achieved MMR. The 12-month PFS was 73.3% (95% CI: [43.3%-89.1%]), and the 12-month OS was 88.2% (95% CI: [60.6%-96.9%].

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 fiveNational 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.

Ascentage Pharma's Forward-Looking Statements

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

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 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 26 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) and Olverembatinib, a Biologics License Application (BLA) for sintilimab accepted for review in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 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.

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.

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