On July 14, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and Ascentage Pharma (6855.HK), reported a multifaceted strategic collaboration (Press release, Innovent Biologics, JUL 14, 2021, https://www.prnewswire.com/news-releases/innovent-and-ascentage-pharma-reach-multifaceted-strategic-agreement-including-joint-commercialization-of-olverembatinib-in-china-joint-clinical-development-on-multiple-products-and-equity-investment-301333902.html [SID1234584858]). This collaboration includes: i) the joint commercialization of HQP1351 (olverembatinib) in China; ii) the collaborative clinical development of Bcl-2 inhibitor APG-2575 (lisaftoclax) with the anti-CD20 monoclonal antibody HALPRYZA (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188); and iii) the equity investment in Ascentage Pharma.
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HQP1351, the core drug candidate of Ascentage Pharma, is 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. 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. Innovent will leverage its advantage of broad commercial channel and experienced oncology commercial team to roll out HQP1351 to hospitals and pharmacies at various tiers, in aims to make this novel therapeutic available to the cancer patients in China.
After signing the agreement, Ascentage Pharma will receive an upfront payment of US$30 million from Innovent. 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.
In addition, the two companies agree to jointly explore the possibility of developing the Bcl-2 TKI APG-2575 with the anti-CD20 monoclonal antibody HALPRYZA (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188), in certain indications.
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 subscription price of HK$57.2 per share within the next two years.
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 2000 people. The collaboration with Ascentage pharma adds another near-to-launch innovative medicine HQP1351 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."
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."
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) (Free ASCO Whitepaper) 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)
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. APG-2575 is the first China-developed Bcl-2 inhibitor entering clinical development in China.
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 biosimilar injection)
HALPRYZA,a rituximab biosimilar injection, is a recombinant human/murine chimeric monoclonal antibody drug co-developed and co-commercialized by Innovent and Eli Lilly and Company. 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)
IBI188 (letaplimab), 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, IBI188 (letaplimab) enhanced phagocytosis of tumor cells and cross-activated T cells. Preclinical data showed that IBI188 (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 IBI188 (letaplimab) was well tolerated generally.