Akeso's sBLA for Ivonescimab in 1L Treatment of PD-L1 Positive NSCLC Accepted by NMPA

HONG KONG, July 29, 2024 /PRNewswire/ -- Akeso (9926.HK) is delighted to announce that the supplemental biologics license application (sBLA) for its independently developed, world's first-in-class PD-1/VEGF bispecific antibody drug, 依达方^® (generic name: ivonescimab Injection), as a monotherapy for first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC), has been accepted by the China National Medical Products Administration (NMPA).

Ivonescimab is the world's first bispecific antibody drug approved for the "tumor immunotherapy + anti-angiogenesis" mechanism. The first-line monotherapy treatment of PD-L1 positive (PD-L1 TPS ≥1%) locally advanced or metastatic NSCLC is ivonescimab's second indication, following its approval for the treatment of EGFR-mutant non-squamous NSCLC that has progressed after EGFR-TKI therapy. Ivonescimab is also expected to become a new standard of care treatment option for both first-line and second-line lung cancer therapy.

This new indication application for ivonescimab is based on the HARMONi-2 (AK112-303) study. The Independent Data Monitoring Committee (IDMC) conducted a pre-specified interim analysis of the HARMONi-2 study, showing highly positive results. In the intent-to-treat (ITT) population, ivonescimab monotherapy significantly prolonged progression-free survival (PFS) compared to pembrolizumab monotherapy, with a hazard ratio (HR) significantly better than expected.

"As a researcher and clinician, we eagerly anticipate ivonescimab becoming the new standard treatment for first-line lung cancer, providing a superior 'chemotherapy-free' option for patients," said Professor Zhou Caicun, principal investigator of the HARMONi-2 study and director of the Oncology Department at East Hospital Affiliated To Tongji University. "The success of the HARMONi-2 study underscores the immense value of ivonescimab's synergistic dual anti-tumor mechanism of 'tumor immunotherapy + anti-angiogenesis.'"

Professor Zhou also emphasized that clinicians are looking forward to Akeso seizing the opportunity to establish ivonescimab as the new standard treatment for first-line lung cancer. He encouraged continuous exploration of combination therapies and ongoing global upgrades to standard treatment options, aiming to provide patients with better therapeutic choices.

Dr. Michelle Xia, Founder, Chairwoman, President, and CEO of Akeso, said: "We are thrilled that ivonescimab has achieved a significant milestone in first-line lung cancer therapy shortly after its approval for second-line treatment. We sincerely thank all our colleagues at Akeso for their decade-long dedication and craftsmanship, the experts for their meticulous contributions, and all the participants involved in the projects."

According to Dr. Xia, the approval of ivonescimab for second-line lung cancer therapy and its potential as a superior, chemotherapy-free new standard for first-line treatment fills a clinical unmet need in global lung cancer immunotherapy with bispecific antibodies, providing a more effective solution for patients and fulfilling Akeso's commitment.

Dr. Xia also emphasized that the HARMONi-2 study showcases ivonescimab's superior efficacy and safety, further solidifying its potential as a cornerstone product in tumor immunotherapy (IO). This includes its broad clinical development value and market prospects when used in combination with ADC drugs or other novel anti-cancer drugs. "We look forward to sharing ivonescimab's robust clinical research data with global regulatory agencies to achieve worldwide approval and provide more effective solutions for patients around the globe."

About Ivonescimab

Ivonescimab, known as SMT112 in Summit's license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab's tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.¹ This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days,¹ is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit's license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

About Akeso

Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions.

With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases, with 19 drug candidates in the clinical stage ，including 8 multispecific antibodies. Akeso has successfully promoted the commercialization of three innovative biological drugs, and marketing applications of multiple indications are submitted for 4 new drugs. 安尼可^®, approved for marketing in August 2021, is currently the only differentiated PD-1 monoclonal antibody that applies the IgG1 subtype with modified Fc-nulldomain. 开坦尼^® (PD-1/CTLA-4 bi-specific antibody, Cadonilimab injection) has been granted marketing approval in June 2022, making it the world's first bi-specific antibody drug for tumor immunotherapy and the first bi-specific antibody new drug in China.In May 2024,依达方^® (PD-1/VEGF bi-specific antibody,Ivonescimab injection) ，the first-in-class PD-1/VEGF bi-specific antibody  independently developed by the Company, has been granted marketing approval for the treatment of epidermal growth factor receptor ("EGFR") mutated locally advanced or metastatic non-squamous non-small cell lung cancer ("nsq-NSCLC") ,making it the world's first approved PD-1/VEGF bi-specific antibody. The drug had been granted three Breakthrough Therapy Designations for the treatment of lung cancer by the Center for Drug Evaluation (CDE) .In December 2022, a license agreement with total potential deal value of USD5 billion, plus a low double-digit royalty of product net sales in the authorized countries of the new drug, 依达方^®, set a new record in overseas licensing for the transaction amount of an single innovative drug in China.

Through efficient and breakthrough R&D innovation, Akeso always integrate superior global resources, develop the first-in-class and best-in-class new drugs, provide affordable therapeutic antibodies for patients worldwide, and continuously create more commercial and social values so as to become a global leading biopharmaceutical enterprise.