On August 24, 2021 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported its 2021 interim results and released an update on the recent progress in clinical development, strategic partnerships, and preparation for commercialization (Press release, Ascentage Pharma, AUG 24, 2021, View Source [SID1234586862]).
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During the reporting period, Ascentage Pharma achieved significant progress in areas including clinical development, strategic partnerships, and intellectual properties. In particular, the company reported clinical results on its lead drug candidates in oral presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, validating the promising clinical utility and first/best-in-class potential of its late-stage assets. In strategic collaborations, Ascentage Pharma entered into a major partnership with Innovent Biologics (or "Innovent"), setting the precedence of a large-scale multifaceted collaboration between two leading Chinese innovative biopharmaceutical companies.
Rapidly advancing clinical development with commitment to global innovation
In the first half of 2021, Ascentage Pharma continued to increase its investment in innovation, with the research and development expenses increased by 26.3% year on year, to RMB318 million. The company has rapidly advanced its global clinical development programs, and is currently conducting over 40 Phase I/II clinical trials in the United States, Australia, Europe, and China. Meanwhile, the company has further strengthened its portfolio of intellectual properties, paving the way for its accelerating research and development. As of June 30, the company has 144 issued patents and more than 510 patent applications globally, among of which, 110 patents are issued overseas.
In the six months ended June 30, 2021, Ascentage Pharma has rapidly advanced its drug candidates in clinical development. The third pivotal Phase II study of the company’s lead drug candidate, HQP1351 (olverembatinib), in patients with chronic myeloid leukemia (CML) resistant/intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs), has already completed its patient enrollment. In March 2021, a Breakthrough Therapy Designation for the indication was granted to HQP1351 by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), accelerating the future development of regulatory approval of the product. HQP1351 is the first China-developed third-generation BCR-ABL inhibitor developed for the treatment of patients with TKI-resistant CML, and is designed to effectively target BCR-ABL mutants, including T315I. Prior to the reporting period, the company has already submitted a New Drug Application (NDA) for HQP1351 in China and was subsequently granted the Priority Review status by the CDE.
Lisaftoclax (APG-2575), the first China-developed selective Bcl-2 inhibitor entering clinical development in China, was cleared by the US Food and Drug Administration (FDA) in June 2021 to enter a clinical study evaluating the drug candidate as a single agent or in combination with other antitumor therapies for the treatment of patients with advanced estrogen receptor-positive (ER+) breast cancer or other solid tumors. APG-2575 is currently being investigated in 17 clinical studies in a range of hematologic malignancies and solid tumors, and has thus far showed enormous therapeutic potential.
During the reporting period, the MDM2-p53 inhibitor alrizomadlin (APG-115) was granted an Orphan Drug Designation (ODD) for the treatment of stage IIB-IV melanoma, marking the fifth ODD granted the product. In total, Ascentage Pharma has obtained twelve ODDs, which is a new record in the number of ODDs granted to any Chinese biopharmaceutical company and a manifestation of the company’s capabilities in global innovation.
Demonstrating the therapeutic utility of lead assets with a focus on delivering clinical values
As a global leader in the development of apoptosis-targeting therapies, Ascentage Pharma has continued to demonstrate its capabilities in global innovation by attracting widespread interest at major scientific events and delivering impressive progress with the clinical development of its apoptosis-targeting drug candidates.
In an oral presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma reported updated results from the first-in-human study evaluating the Bcl-2 inhibitor APG-2575, another core drug candidate of the company’s apoptosis-targeting pipeline, in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies. These results of APG-2575 demonstrated favorable preliminary safety and efficacy, including an objective response rate (ORR) of 80%, and a good tolerability profile with manageable adverse events (AEs). Moreover, no dose-limiting toxicity (DLT) was observed at the maximum tested dose of 1,200 mg. The maximum tolerated dose (MTD) has not been reached, and no laboratory or clinical tumor lysis syndrome (TLS) has been reported. These data are indictive of APG-2575’s potential as an alternative treatment with clear best-in-class potential.
In another oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, the company released updated results from a Phase II study of APG-115, which is also a lead candidate in Ascentage Pharma’s apoptosis-targeting pipeline, in combination with pembrolizumab in patients with unresectable or metastatic melanoma or advanced solid tumors that have progressed on prior immuno-oncologic (IO) drugs. These results demonstrated a manageable safety profile and meaningful clinical antitumor activity, including one patient with a complete response (CR), an objective response rate (ORR) of 24.1% and a disease control rate (DCR) of 55.2%. In addition, partial responses (PRs) were reported in enrolled patients with other tumor types. These results showed APG-115’s potential as a first-in-class therapy for patients resistant or refractory to prior IO drugs. Furthermore, the preclinical results of APG-115 published in the renowned scientific journal, Nature Immunology, in March this year has demonstrated MDM2’s pivotal biological role in T-cell stability, survival, and antitumor immunity, potentially laying a foundation for synergistic effects between MDM2-targeted agents such as APG-115 and cancer immunotherapy.
Expanding external collaborations through multiple new landmark partnerships
In the first six months of 2021, Ascentage Pharma entered into a landmark strategic partnership with Innovent, setting a new partnering model between innovative biopharmaceutical companies in China. According to the terms of the agreement, the two companies will jointly develop and commercialize one of Ascentage Pharma lead drug candidates, the third-generation BCR-ABL inhibitor, HQP1351; jointly develop Ascentage Pharma’s Bcl-2 inhibitor, APG-2575, 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). Moreover, the two companies agreed that Innovent will subscribe to Ascentage Pharma’s common shares for a total consideration of US$50 million at HK$44.0 per share (subscription completed), and to grant Innovent 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 (pending approval at shareholder meeting). Having entered this strategic collaboration that created a new partnering model for the development of innovative therapies, the two companies will collaborate in every possible manner to accelerate the introduction of China-developed innovative therapies to the world and bring clinical benefit to more patients in need.
While building win-win partnerships in China, Ascentage Pharma has actively sought new partners overseas. To accelerate its global innovation, the company has entered into a Cooperative Research and Development Agreement (CRADA) with the world-leading research institute, the National Cancer Institute (NCI), to collaborate on the non-clinical and clinical development of Ascentage Pharma’s drug compound APG-1252 (pelcitoclax). This collaboration with the NCI will help Ascentage Pharma to maximize the clinical potential of APG-1252 in solid tumors and further strengthen the company’s pipeline.
Also during the reporting period, Ascentage Pharma received another milestone payment from its global licensee, UNITY Biotechnology, after UNITY reported positive data from a Phase I clinical study of the senolytic drug candidate UBX1325, and dosed the first patient in the subsequent Phase IIa clinical study. In the future, Ascentage Pharma will continue to work closely with UNITY in the development anti-aging drugs that will bring hope to patients around the world.
Steady progress in commercialization and industrialization in preparation for upcoming product launches
To support the company’s commercialization activities and the rollout of its global strategies, Ascentage Pharma commenced the construction of its Global Headquarters, R&D center, and manufacturing facility in November 2019. Since then, the construction has progressed rapidly and the facility will likely to be ready for operations later this year to accelerate the company’s transition from a clinical-stage biotech into a full-fledged global biopharmaceutical company, further extending the company’s global outreach. While entering into the agreement with Innovent on the joint commercialization of HQP1351, Ascentage Pharma has built a commercial team processing a strong track record in the field of hematology. This talented team is currently in all-out preparation for the upcoming launch of the company’s lead drug candidate HQP1351, laying down a solid foundation that will enable the future commercial success.
Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, commented: "In the first half of 2021, Ascentage Pharma achieved tremendous progress in clinical development, external collaborations, and commercialization preparation. Clinical progress with two of our lead apoptotic assets, APG-2575 and APG-115, reported in oral presentations at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, demonstrated our robust progress in research and development, and further validated the clinical value and potential of our assets. Meanwhile, we entered into a large-scale multifaceted strategic collaboration with Innovent. This collaboration will generate strong tailwind to the commercialization of our lead compound, HQP1351, and the clinical development of APG-2575. The equity investment from Innovent signifies strong recognition of our R&D capabilities and our growth potential.
Moving forward, we will press ahead with the commercialization of HQP1351 and reach the milestone of our first commercial launch as soon as possible. We will continue to accelerate our clinical programs globally and steadfastly implement our global innovation strategy. To move us closer to realizing the mission of addressing unmet clinical needs in China and around the world, we will strive to bring more safe and effective therapies to patients and to create additional value for our shareholders."