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KN026+KN046
Pipeline Programs
  • Envafolimab(KN035)
  • KN046
  • KN026
  • JSKN003
  • KN026+KN046
  • KN019
  • JSKN033
  • JSKN016

    JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (ADC), which is developed inhouse with proprietary Glycan-specific conjugation platform. Through enzyme catalysis and click chemistry, the payloads are site-specifically linked to glycan on Fc. The glycan structure is precisely controlled via process engineering which renders consistent DAR with more favorable stability. Upon binding with HER2, JSKN003 induces clustering of the receptor and triggers extensive internalization the JSKN003-Her2 complex. The internalization leads to release of payload that kills tumor directly or via and by stander effect.

    JSKN00301
    JSKN003:Product Structure

    Comparing with other ADC drugs, JSKN003 induces faster and more intense endocytosis , which leads to stronger bystander effect in HER2-expressing tumors. Meanwhile the better serum stability ensures much wider therapeutic window. For example, JSKN003 shows better safety profile in preclinical study and similar tumor killing activity with Enhertu (DS-8201) in both high and low HER2 expression model (CDX+PDX).

    JSKN003机制图

     

    JSKN003 is carrying out a series of clinical studies in Australia and China, and has entered the phase III clinical stage in China for HER2 low expression breast cancer indications.

     

     

    KN019 is a biosimilar of Belatacept (Nulojix®), an immunosuppressive agent approved for prophylaxis of organ rejection in adult patients receiving a kidney transplant. As a fusion protein composed of the Fc-fragment of a human IgG1 immunoglobulin linked to the extracellular domain of CTLA-4, Belatacept acts as a selective T cell co-stimulation blocker. Belatacept’s superior efficacy profile has been demonstrated in long-term outcome studies*.

     

    KN019 : Crystal Structure

    Belatacept is an improved version of Abatacept (Orencia®) with higher potency. Orencia is approved for rheumatoid arthritis, idiopathic arthritis, and psoriatic arthritis.

     

    KN019 has started phase II trial for rheumatoid arthritis in August 2019 and will expand to oncology-related indications in the future.

    Due to its structure of a fusion protein with complex glycosylation, Belatacept is very difficult to manufacture as the biosimilar product. So far, few companies are able to develop a competitive biosimilar of Belatacept. In contrast, KN019 has demonstrated robust CMC and superior quality in multiple batches of large-scale production.

    KN019表格-en

    JSKN033 is the world's first subcutaneous fixed-dose combination (FDC) developed by Alphamab Oncology, consisting of JSKN003 and envafolimab. JSKN003 is a HER2-directed antibody-drug conjugate (ADC), comprising of three components: a bispecific antibody targeting two non-overlapping epitopes of HER2 extracellular domains, a cleavable linker, and a topoisomerase inhibitor. The envafolimab, the other component of the FDC, is a Fc fusion protein consisting of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment, which has been approved by China NMPA for the treatment of MSI-H or dMMR advanced solid tumors as the first subcutaneously administered PD-L1 inhibitor.

    JSKN03301
    作用机制

    Compared with other anti-HER2 ADCs, JSKN003 induces more endocytosis in HER2-expressing tumors and stronger bystander effect in Her2 negative tumors. In addition, JSKN003 shows much better serum stability. These characteristics ensure JSKN003 maybe have much wider therapeutic window. JSKN003 is carrying out a series of clinical studies in Australia and China, and has entered the phase III clinical stage in China for HER2 low expression breast cancer indications. Envafolimab is the global first subcutaneously administered PD-L1 inhibitor and marketed in China. Based on its unique design, envafolimab offers advantages in terms of safety, convenience and compliance, eliminating the need for patients to have intravenous drips, while at the same time having low healthcare costs. KN035 is currently undergoing clinical studies in multiple oncology indications in China, the United States and Japan, and several indications have entered phase III registration. JSKN033 is expected to provide effective innovative therapy for patients and doctors through IO and ADC combo and have better safety profile and convenience due to the nature of SubC injectables. JSKN033 has received approval from the Australian Bellberry Clinical Research Ethics Committee to conduct clinical studies for the treatment of HER2-expressing advanced or metastatic solid tumors.

     
    JSKN033-表格(en)

    JSKN016 is a bispecific antibody conjugated drug (ADC) developed inhouse with proprietary Glycan-specific conjugation platform,which can simultaneously target HER3 (Human epidermal growth factor receptor 3) and TROP2 (Trophoblast cell surface antigen 2).

    JSKN01601
    JSKN016:Product Structure

     

     

    After binding with TROP2 or HER3 on the surface of tumor cells, JSKN016 enters the lysosome through target-mediated endocytosis, releasing cytotoxic topoisomerase I inhibitor (TOPIi), and then inducing tumor cell death. In addition, the inhibitor can penetrate the cell membrane and enter the antigen-negative tumor cells to exert bystander effect. These effects can effectively inhibit the growth of tumor cells.

    图片10

     

    The clinical study of JSKN016 for the treatment of advanced malignant solid tumors has been accepted by the CDE.