Our unique modular platform technology combines genes with desired properties to make novel compounds by creating a new code
Nykode Therapeutics' technology platform rethinks conventional drug design through its intelligent modular design and tailored hyper targeting, tailored for the specific disease. The platform opens the door to unlimited possibilities and truly unique modalities within multiple therapeutic areas.
Nykode Therapeutic’s proprietary, targeted immunotherapy platform centers around the Vaccibody molecule format designed to induce potent, long-lasting and specific immune responses. The specificity of the targeting unit of the Vaccibody molecule determines to which subsets of Antigen Presenting Cells (APC) or cell type the antigen is delivered, which may critically influence the associated immune response.
CCL3L1, C-C motif chemokine ligand 3 like 1, is so far the most used targeting unit in Nykode’s vaccine candidates and part of several vaccine candidates undergoing clinical development. CCL3L1 targeted immunotherapies have been shown to have a unique ability to attract and stimulate APC’s capable of eliciting broad, strong and dominant CD8 T cell responses combined with supporting CD4 helper T cell responses. CD8 T cell responses are key to killing tumor cells but are also important for controlling infected cells in an infectious disease setting.
The unique ability to induce broad and strong T cell responses distinguishes Nykode’s platform from both conventional vaccines, including non-targeted DNA vaccines, RNA vaccines and peptide-based vaccines. Vaccine candidates based on the modular Vaccibody molecule are well tolerated and therefore may have the potential to be used in combination with other therapeutic modalities such as immune check-point inhibitors.
The recombinant Vaccibody protein consists of three modules:
The targeting unit directs the antigens to the immune system’s Antigen Presenting Cells (APC). The targeting unit is fully flexible and can be designed to deliver T cell epitopes or antigens specifically to certain subset of APC optimizing the desired effect. This controlled delivery allows for induction of a specific immune response profile that correlates with protection for each specific disease, e.g., antibody, CD4 (Th1/Th2/Th17)- and/or CD8 T cell responses; or in the case of tolerizing vaccines, induces proliferation of antigen specific T regulatory cells.
The dimerization unit joins the two protein chains into the dimeric Vaccibody format. The dimeric format is designed to facilitate attraction, activation and internalization into the APC by crosslinking receptors on the surface of the APC.
The antigenic unit contains the epitopes and antigens selected, to which a specific immune response is warranted. Epitopes and antigens may be selected to address a vast range of diseases, including cancer, infectious diseases and autoimmune diseases. The flexibility of the platform allows for a broad immune response and for inclusion of large globular antigens and multiple sets of T cell epitopes.
A targeted vaccine – mechanism of action
The Vaccibody™ vaccines in the clinic to date are delivered as a DNA plasmid using a needle-free jet injector that delivers the plasmids into the muscle cells. Inside the cells, the DNA plasmids provide the information to produce the Vaccibody protein in the same way that cells produce other human proteins. The newly encoded Vaccibody™ proteins are then secreted from the cells and target and recruit the APC. Depending on the choice of targeting unit, different subsets of APCs will be targeted, meaning the immune response may be skewed towards humoral (antibodies) or cellular (T cells) or variations of those (CD8/CD4, Th1/Th2/Th17/Treg). For example:
A: The Vaccibody™ protein may bridge and APC and a B cell and thus form an APC-B cell synapse, which may lead to rapid and strong B cell activation responsible for mediating the production of antigen-specific antibodies. These antibodies may then neutralize a pathogen such as a virus.
B: The Vaccibody™ protein may bind and cross-link two receptors on the APC, which provides an important signal to the APC for downstream processing. The ligation leads to receptor-mediated internalization and the antigens from the Vaccibody™ protein are then processed and antigenic epitopes are presented on MHC class I and MHC class II molecules to CD4 and CD8 T-cells. This results in an antigen-specific T cell response. In the case of the MIP-1α targeting unit, cross-presentation, and thus loading of epitopes on MHC class I, and activation of the CD8 killer T cells are particularly effective, and these cells are responsible for directly killing the cancer cells or cells infected by a pathogen, like a virus.
The off-the-shelf vaccine
Off-the-shelf cancer and infectious disease vaccines offer a fast, scalable and attractive approach to cancer treatment. Such vaccines target shared antigens which are found pathogens or expressed by tumors across large patient populations. We have built significant experience in off-the-shelf vaccines, from our infectious disease programs and our VB10.16 clinical program in HPV16-driven cancer types. To expand our clinical pipeline, we are focusing parts of our research efforts on identifying both shared cancer antigens and developing additional off-the-shelf vaccines within the field of cancer, infectious diseases as well as future potential within autoimmune disorders.
The individualized cancer vaccine
A fully individualized vaccine requires rapid turnaround time and robust processes across the entire value chain to enable manufacturing of one vaccine specifically designed to each patient. We have entered an exclusive worldwide license and collaboration agreement with Genentech for our individualized neoantigen cancer vaccines. The experience from our VB N-01 clinical trial testing VB10.NEO indicates that we have a competitive advantage in the manufacturing process, demonstrated by 100% manufacturing success rate for all patients with a sufficient number of neoantigens. The unique mechanism of action leading to rapid, strong and CD8-dominating responses has also led to highly encouraging immunological and clinical signs of efficacy in the first patients evaluated.