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 Therapeutics’ proprietary modular Vaccibody technology centers around the ability to induce fast, strong and long-lasting specific immune responses by targeting antigens to antigen presenting cells. The Vaccibody molecules consists of three functional units; a targeting unit that binds to surface receptors on antigen presenting cells, a dimerization unit and an antigenic unit that is derived from the disease-causing agent, e.g. from a cancer cell or pathogen. The genes for each unit are genetically linked and encode a novel fusion protein called the Vaccibody protein. This platform can be used to encode a range of different targeting units and antigenic units and thus fuel multiple novel products.
The selected targeting unit determines the delivery of the antigen to specific subsets of APC or cell type, which ultimately affects the kinetics and immune response profile. The MIP-1 α targeting unit used in Nykode’s two clinical Vaccibody products has been selected because it attracts APC and induces rapid, strong and dominant CD8 killer T cell responses, combined with supporting CD4 helper T cell responses. CD8 killer T cell response has been shown to be important for killing tumor cells and pathogen-infected cells. The important role of T cell responses in infectious diseases has become more evident in the current COVID-19 pandemic. The unique ability to induce a strong CD8 killer T cell response is dependent on the MIP-1alpha targeting unit and distinguishes the Vaccibody MIP-1a products from conventional vaccines, including non-targeted DNA vaccines, RNA- and peptide-based vaccines. The Vaccibody vaccine has demonstrated a favorable safety profile and has the potential to be used in prophylactic settings as well as in early lines of cancer therapy and with several combination therapies where applicable.
The recombinant Vaccibody protein consists of three modules:
The targeting unit targets and delivers the antigens to the immune system’s Antigen Presenting Cells (APC). It can be selected to optimize delivery of the antigen to the optimal subset of APC. 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/Treg)- and/or CD8 T cell responses.
The dimerization unit joins the protein into the dimeric Vaccibody™ format. The dimerization helps facilitate attraction, activation and internalization into the APC by crosslinking receptors on the surface of the APC. It has an additional function bridging an APC and B cell through a B-cell receptor recognizing the antigen which can form an APC-B cell synapse triggering rapid and strong antibody responses.
The antigenic unit includes the selected antigens, to which a specific immune response is generated. These can be selected to fight a vast range of disease areas, including cancer and infectious 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 as well as combinations of both.
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.