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JSKN003
Pipeline Programs
  • Envafolimab(KN035)
  • KN046
  • KN026
  • KN026+KN046
  • KN019
  • KN052
  • JSKN003

    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, and it achieved global sales of about US$2.7 billion in 2017.


    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.

    KN052 is a PD-L1/OX40 bispecific antibody developed by Alphamab Oncology using the company's bispecific antibody platform. It can simultaneously bind PD-L1 and OX40, effectively reversing tumor induced immune inhibition by blocking the PD-L1/PD-1 pathway and promoting the immune response by agonizing OX40. KN052 prevents the immune escape of tumor cell, on the other hand, it activates CTL T cells and attenuates Treg-mediated immunosuppression. Through synergistic mechanisms, KN052 is expected to exert strong antitumor efficacy.

     

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    KN052:Product Structure

     

    PD-L1 antagonist and OX40 agonist activity in one molecule;tandem structure for antigen binding domain arrangement to attenuate anti-OX40 toxicity;wildtype IgG1 Fc with full Fc function to enable depletion of Tregs overexpression OX40. OX40 is a member of key class of T cell costimulatory molecules. OX40, through interaction with OX40L, plays key role in survival and amplification of effector T cells and memory T cells and induce cytokine secretion. It can be used as an adjuvant in combination with tumor vaccines and cell therapy.

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    In preclinical studies, KN052 showed significantly stronger activity than single antibody or in combination. In February 2022, the IND for KN052 was approved by the National Medical Products Administration (NMPA) to initiate Phase I clinical trials in China. The first patient was dosed in the KN052-CHN-001 PhaseⅠtrial of KN052 in June 2022.

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    KN052

    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.


    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

     

    An open-label, dose-escalation, first-in-human Phase I trial in Australia is ongoing to assess safety and tolerability in patients with advanced or metastatic solid malignancies and to determine the maximum tolerated dose /RP2D. The IND of JSKN003 in China has also been approved by NMPA.

     

     

    JSKN003-表格1(en)