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Pipeline Programs
  • KN035
  • KN046
  • KN026
  • KN019

    KN035* is an investigational PD-L1 antibody currently being evaluated in broad clinical studies in the US, China, and Japan. It is created by a fusion of the of PD-L1 domain antibody with the Fc domain of a regular antibody. Compared with conventional PD-(L)1 antibodies currently approved and under development, KN035’s unique design makes a differentiated and competitive profile: better tumor tissue penetration in animal model studies, subcutaneous injection, high affinity and stability, low immunogenicity, mutated Fc domain to eliminate ADCC/CDC activity, and comparable in vivo half-life.

    KN035 : Crystal Structure

    Current PD-(L)1 therapies in the market require frequent intravenous administration, a major drawback to compliance and convenience. Furthermore, there is a growing population of cancer patients who need more user-friendly PD-(L)1 therapies:

    Many patients have gone through multiple cancer treatments with intravenous administration, such as chemotherapy and target therapy. The difficulty of finding adequate veins for the site of injection becomes a significant challenge to intravenous-based treatment.
    Due to the recent advance in cancer therapies, many cancer patients are able to lead a normal life, with their cancer in remission, but they need maintenance therapies to keep fighting the residual cancer cells. For these patients, returning to the hospital or clinic for hour-long intravenous injections can impact their quality of life.

    KN035 is the only classic subcutaneous formulation among PD-L1 antibody therapeutics, on the market or under development. It can be injected easily without the need for a vein, significantly shortens the time required for administration (in seconds), and has the potential for home-use injection, creating an improved quality of life for patients.

      Zhang F, Wei H, Wang X, et al. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discovery, 2017, 3:17004.

    KN046 is a PD-L1 – CTLA-4 bispecific antibody currently in phase II clinical trials. 

    PD-L1 and CTLA-4 are the two most validated immuno-oncology targets, and combination therapies of PD-L1 and CTLA-4 are already approved for melanoma and renal cell carcinoma. Such combinations are also in multiple late-stage clinical trials, showing the massive market potential of a safer and efficacious drug aimed at both these targets. However, high toxicity of current CTLA-4 antibodies limits their therapeutic utility.

    We have developed KN046, a PD-L1 – CTLA-4 bispecific with a few innovative designs:

    A proprietary CTLA-4 domain antibody with a much-improved safety profile;
    Engineered to target the tumor microenvironment and limiting the CTLA-4 arm's function to the tumor site.

    The preclincial and clinical study results for KN046 have shown a profile of promising efficacy and lower toxicity, in support of the above strategy. Such novel designs make KN046 well ahead of peer PD-(L)1 – CTLA-4 bispecific competitors, with the potential to become the cornerstone of immuno-oncology therapy in the future.

    KN026*  is an anti-HER2 Fc-based heterodimer bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, leading to a dual HER2 signal blockade. KN026 is currently in phase II clinical trial in China, and in phase I clinical trial in the US. KN026 is on fast track for regulatory review and approval by the NMPA. 

    KN026 : Crystal Structure

    In pre-clinical studies, KN026 has demonstrated a much-improved profile over combination of Trastuzumab and Pertuzumab, such as increased binding affinity, as well as better efficacy in 40% of HER2 expression tumor cell lines screened.

    The CMC process for KN026 has been well validated by multiple large-scale (250 L to 1000 L) batches, and it consistently delivers a world-class process as robust as those for regular homodimer antibody, such as in yield, purity and stability.

    The global sales for Trastuzumab and Pertuzumab is currently about US$10 billion a year. Given its superior profile, KN026 is positioned to be a best-in-class candidate in a sizable global market for HER2-positive tumors.

    *  Wei H, Cai H, Jin Y, et al. Structural basis of a novel heterodimeric Fc for bispecific antibody production. Oncotarget, 2017, 8(31): 51037.

    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*.

    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 $2.7 billion in 2017.

    KN019 is planned to start a phase II trial for rheumatoid arthritis in August 2019 and expand to oncology-related indications in the future. 

    Due to its fusion protein structure with complex glycosylation, Belatacept is very difficult to manufacture, especially from the biosimilar perspective. So far, few parties in the industry 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.