Ascentage Pharma and Innovent Biologics Reach Multifaceted Strategic Agreement Totaling US$245 Million Including Commercialization of Olverembatinib (HQP1351) in China, Joint Clinical Development of Lisaftoclax (APG-2575) and Equity Investment

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Jul 14, 2021, 13:43 ET

SUZHOU, China, and ROCKVILLE, Md., July 14, 2021 /PRNewswire/ -- Ascentage Pharma (6855.HK), a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, and Innovent Biologics (1801.HK, "Innovent"), today announced a multifaceted strategic collaboration. This collaboration includes the joint clinical development and commercialization of HQP1351(olverembatinib), a third-generation BCR-ABL inhibitor and a core drug candidate of Ascentage Pharma, in China; the collaborative clinical development of Ascentage Pharma's Bcl-2 inhibitor APG-2575(lisaftoclax) in combination with the anti-CD20 monoclonal antibody HALPRYZA® (rituximab biosimilar injection) co-developed by Innovent and Eli Lilly and Company, and Innovent's anti-CD47 monoclonal antibody letaplimab (IBI188). Furthermore, Innovent will subscribe to Ascentage Pharma's common shares for a total consideration of US$50 million at HK$44.0 per share, and be granted stock warrants that will allow it to acquire additional Ascentage Pharma's common shares for a total consideration of US$50 million at a subscription price of HK$57.2 per share. This agreement marks a large-scale multifaceted collaboration between two leading Chinese innovative biopharmaceutical companies.

Key components of the agreement:

The joint clinical development and commercialization of HQP1351 in China

Upon signing the agreement, Ascentage Pharma will receive an upfront payment of US$30 million from Innovent.
Joint clinical development and commercialization: According to the agreement, Innovent and Ascentage Pharma will be jointly responsible for the subsequent R&D of HQP1351 in China. Upon being granted a New Drug Application (NDA) approval, the two companies will jointly commercialize HQP1351 in China and equally split the profit generated by the joint commercialization.
Milestone payments: upon achieving certain pre-specified milestones in development, registration and annual sales performance of HQP-1351, Ascentage Pharma is eligible to receive up to US$115 million in milestone payments.

The joint clinical development of APG-2575 in China

The two companies agree to jointly explore the development of APG-2575 with the anti-CD20 monoclonal antibody HALPRYZA® (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188) in certain indications.

Investment in equity and stock warrants

Innovent agrees to purchase US$50 million worth of Ascentage Pharma's common stock at HK$44.0 per share.
Ascentage Pharma will grant Innovent stock warrants that will allow it to acquire additional Ascentage Pharma's common shares for a total consideration of US$50 million. These warrants will be issued at a subscription price of HK$57.2 per share, exercisable within two years upon and after the approval of shareholder meeting of Ascentage Pharma. Ascentage Pharma retains the right to redeem the warrants if Innovent decides not to exercise the warrants within six months of the stock price remaining above HK$57.2 per share.

Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, stated: "Innovent is a leading biopharmaceutical company with outstanding integrated capabilities in the R&D and commercialization of innovative therapies. It is our great pleasure to enter into this multifaceted and comprehensive landmark partnership with Innovent. HQP1351 is a novel therapeutic with practice-changing potentials. We hope that by leveraging the two companies' expertise in clinical development, we will be able to quickly expand the indications of HQP1351. Another one of our assets, APG-2575, is the world's second, and China's first Bcl-2 inhibitor that has demonstrated compelling clinical activity with best-in-class potential. As a small-molecule drug, APG-2575's potential utility in combination with Innovent's anti-CD20 monoclonal antibody and anti-CD47 monoclonal antibody is very promising. The equity investment in Ascentage Pharma is a major strategic investment signifying Innovent's strong recognition of our R&D capabilities and our growth potential, and generates powerful tailwind to our global clinical development programs. Moreover, this collaboration between two companies with shared company cultures and mission is groundbreaking for China's biopharmaceutical industry. We hope this partnership between the two companies will accelerate the development of innovative therapeutics in China and benefit more patients around the world."

Dr. Michael Yu, Founder, Chairman and CEO of Innovent Biologics, stated: "We are excited to form this strategic collaboration with Ascentage Pharma, a pioneer in the field of innovative R&D of apoptosis-targeted therapies. Innovent is deeply engaged in the oncology area having built up a robust oncology pipeline of nearly 20 clinical stage assets, an industry-leading medical operations and regulatory affairs team, a broad commercial channel and a professional commercial team of over 2,000 people. The collaboration with Ascentage Pharma adds another near-to-launch innovative medicine HQP-1351 to our pipeline, and we will leverage our advantage in the joint commercialization after the drug is approved. In addition, this collaboration creates potential synergy with our oncology pipeline such as CD47 and CD20 antibodies. Meanwhile, we are impressed with Ascentage Pharma's strong R&D capability and rich pipeline, and we hope to join in our partner's growth potential realization through the strategic equity investment. We look forward to partnering with Ascentage Pharma and bringing the innovative therapies of both parties to patients as soon as possible.

The strategic collaboration represents a new model for China biopharmaceutical companies to work together to bring additional benefit to patients. Innovent has been exploring diversified and innovative strategic partnership models with outstanding pharmaceutical companies globally with the aim to make more innovative therapies available. This collaboration proves once again that Innovent is an ideal partner to help expand pipeline development and product commercialization."

Background of the Collaboration

HQP1351 is a BCR-ABL tyrosine kinase inhibitor (TKI) designed to effectively target a spectrum of BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). At present, an 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.

This partnership is designed to leverage the two companies' strengths in clinical development, commercialization, and channel expansion will help further explore the value of HQP1351 as well as accelerate its indication expansion. The two companies are set to jointly build a highly competitive team in hematologic malignancies to rapidly roll out HQP1351 to hospitals and pharmacies at various tiers, in aims to make this novel therapeutic available to a broad population of cancer patients in China.

APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. It is worth noting that APG-2575 is also the world's second, and China's first selective Bcl-2 inhibitor that has demonstrated promising clinical activity. Ascentage Pharma released data in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrating a promising objective response rate (ORR) of 80% with APG-2575 as single agent in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL). Moreover, Bcl-2 inhibitors have broad therapeutic utility and combinatory potential in the treatment of B-cell malignancies.

HALPRYZA® (rituximab injection), co-developed and co-commercialized by Innovent and Lilly, is a high quality anti-CD20 monoclonal antibody, which binds to the CD20 antigen on the surface of B lymphocytes and mediates complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Normal and malignant B cells are targeted for destruction by the antibody, thereby achieving anti-tumor and immunosuppressive therapeutic effects. HALPRYZA® (rituximab injection) is approved by NMPA for diffuse large b cell lymphoma (DLBCL), follicular lymphoma (FL), and CLL. Letaplimab (IBI188) is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47, which blocks phagocytosis of macrophage by binding to the signaling regulatory protein (SIRP) on the surface of macrophage, to send a "don't eat me" signal. A Phase 1a study of letaplimab (IBI188) has showed promising preliminary safety, good tolerability and anti-tumor activity. Letaplimab (IBI188) is currently undergoing Phase 1b studies for the treatment of myelodysplastic syndromes (MDS) and AML.

Bcl-2 inhibitors have strong combinatory potential with anti-CD20 and anti-CD47 monoclonal antibodies. This partnership aims to realize the potential synergy between Ascentage Pharma's portfolio of leading small-molecule assets and Innovent's cutting-edge platform of large-molecule biologics. Moving forward, both companies will leverage their strengths in clinical development, expand access to hospitals, and enhance R&D efficiency.

About Olverembatinib (HQP1351)

Being developed by Ascentage Pharma, HQP1351 is a novel, orally active, potent third-generation BCR-ABL tyrosine kinase inhibitor (TKI) designed to effectively target a spectrum of BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). Since 2018, the clinical results of HQP1351 have been selected for oral presentations at American Society of Clinical Oncology (ASCO) Annual Meeting for three years in a row. At present, a New Drug Application (NDA) for HQP1351 has been submitted in China, and the application was subsequently granted the Priority Review status. Moreover, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study, and was subsequently granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA.

About Lisaftoclax (APG-2575)

At present, APG-2575 has been cleared and approved to enter multiple Phase Ib/II studies in the US, China, Europe, and Australia, and is being developed globally for the treatment of multiple hematologic malignancies including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and breast cancer. To date, APG-2575 has been granted five ODDs by the US FDA for the treatment of Waldenström macroglobulinemia (WM), CLL, multiple myeloma (MM), AML, and follicular lymphoma (FL).

About HALPRYZA® (rituximab injection)

HALPRYZA®, a rituximab biosimilar injection, is a recombinant human/murine chimeric monoclonal antibody drug co-developed and co-commercialized by Innovent and Lilly. Rituximab binds to the CD20 antigen on the surface of B lymphocytes and mediates complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Normal and malignant B cells are targeted for destruction by the antibody, thereby achieving anti-tumor and immunosuppressive therapeutic effects. In China, HALPRYZA® is approved by National Medical Products Administration (NMPA) for diffuse large b cell lymphoma (DLBCL), follicular lymphoma (FL), and CLL.

About letaplimab (IBI188)

Letaplimab, or IBI188, developed by Innovent Biologics, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. CD47 is a transmembrane protein that blocks phagocytosis of macrophage by binding to the signaling regulatory protein (SIRP) on the surface of macrophage, to send a "don't eat me" signal. After blocking this myeloid checkpoint, letaplimab enhanced phagocytosis of tumor cells and cross-activated T cells. Preclinical data showed that letaplimab had clear target, clear mechanism of action and significant efficacy. Phase 1a clinical data showed that the escalation of all the preset doses has completed, with the highest exploratory dose of 30mg/kg QW. No dose-limiting toxicity occurred in each dose group, and letaplimab was well tolerated generally.

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. HQP1351, 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 11 ODDs from the US FDA for 4 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. Ascentage Pharma aims to continuously strengthen its R&D capabilities and accelerate its clinical development programs 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 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 25 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 14 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.

Note:

Sintilimab is not an approved product in the United States.

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

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab 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.

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Innovent Biologics, Inc. Forward-Looking Statements

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