Interview Defence Therapeutics: Platform strategy the key to success

Our technology essentially modifies a particular protein by chemically attaching a small unit called Accum™ to it. Specifically, we can do this with antibodies or even DNA and RNA and modify them using our Accum™ technology. Once the biologic is taken up by the target cell and sorted into the endosomes, the Accum moiety breaks down the endosomal membrane, minimizing the non-specific degradation that occurs during endosomal maturation. Thus, the biologic is delivered to the cytoplasm of the cell in a native and undamaged state. If the product is an antigen, it is efficiently degraded by the proteasome machinery, resulting in effective peptide presentation to immune cells. If the product is an ADC, the drug is efficiently transported into the cytoplasm or nucleus of the cancer cell. To put it in simple terms, Accum™ helps us target active ingredients precisely to the origin of infections or diseases.

Although Defence has several products in the pipeline, they are all based on our Accum™ technology. For example, the technology helps us improve the therapeutic index of a particular antibody or ADC. The technology can also be used for vaccinations against infectious pathogens. To treat cancer directly, you can inject the Accum™ molecule, which is toxic on its own. Accum™ is the perfect example of a versatile platform.

Accum™ induces endosomal escape into the cytoplasm. Or in simple terms, it helps ensure that active ingredients arrive unharmed where they are needed from a therapeutic perspective. Without Accum™, many drugs would be destroyed due to the acidic milieu in the endosomal microenvironment. Our technology ensures that active ingredients are brought to where they have the best effect in the most effective way, undamaged.

On the one hand, there is the area of antibody-drug conjugates (ADCs) for the effective delivery of chemotherapy. In this way, we deliver active substances precisely to the respective cells and support a very specific therapy. The second application is vaccines. Using Accum™, we protect specific proteins, such as RNA or DNA, from non-specific damage. The third application is direct injection using our AccuTOX approach. Since Accum™ behaves like a toxic molecule on its own, it can also be used in isolation for therapy.

The vaccine was given to animals with established lymphoma. Untreated, all animals would die in less than three weeks. When vaccinated with our vaccine, 7 out of 10 mice showed a response to the vaccine. More precisely, tumor growth was controlled in some animals, and the tumor regressed in others. The mice survived up to eight weeks.

Yes, indeed. We are currently working on a second-and third-generation vaccine that uses multiple variants of the Accum™ moiety. Not only would this allow us to use better-acting Accum™ moieties, but it would also allow us to be faster and more efficient in breaking through endosomal membranes. In addition, we are testing different combinations with the vaccine, such as the use of immune checkpoint inhibitors (CTLA4, PD-1, LAG3...) and pro-inflammatory cytokines (IL-2, IL-12, IL-15...).

In sum, the Accum platform is highly versatile and can lead to various therapeutic applications. These include:

• The development of novel ADCs
• Optimizing currently available ADCs with limited efficacy
• The development of a protein-, DNA- or RNA-based vaccine for both cancer and infectious diseases
• Enhancing CRISPR delivery and efficacy

We are currently in discussions to gain access to a suitable space in a hospital to manufacture our vaccine. Once this step is completed and we have identified the site, we will proceed with regulatory agencies such as Health Canada or even the US FDA and begin our Phase I clinical trial.

We will continue our work in a committed and focused way! We will soon demonstrate how our vaccine can be used in concrete applications: One focus is on treating cancer with specific tumor-associated antigens, but we also see opportunities for our technology around SARS-Cov-2. We also intend to extend our vaccine platform to other infectious diseases.

We are currently well funded to meet near-term goals and create value for shareholders. As soon as we have defined further targets, we will inform the financial market. Transparent communication around our technology and its further development go hand in hand with the questions of financing. Our shareholders have a right to be informed about all details. As our solutions are innovative and sometimes complex for laypeople to understand, we attach great importance to targeted communication so that investors can evaluate our progress and our perspective.