Defence Therapeutics
Enhancing Drug Delivery with Next-Generation Platform Technology

Targeted delivery of antitumor agents is of great interest in cancer therapy. The ability to precisely direct potent therapeutics makes treatments more effective and prevents debilitating side effects. However, efficient nuclear drug delivery through systemic administration remains challenging due to physiological barriers like elimination through renal excretion and the mononuclear phagocyte system (MPS), cellular uptake as well as endosomal escape, and the double-layered nuclear membrane.

Defence Therapeutics, a Canadian biotech developing next-generation biopharmaceutical innovations for various immuno-oncology (IO) and infectious diseases (ID) indications, is tackling this industry-wide nuclear localization-related antibody-drug conjugate (ADC) challenge. Accum is the first solution to enable ADCs to control the intracellular delivery of chemotherapeutic drugs, resulting in a superior preclinical antitumor activity that can overcome problematic cell recycling and rejection patterns. It also increases tumor targeting specificity with its ability to boost drug accumulation, significantly reducing non-specific toxicity in healthy cells.

Using Accum, drug developers can recycle a molecule that failed phase two due to dosage, effectiveness, or potency issues and create a novel agent with a multi-fold improvement over the original product. Alternatively, Accum can be used with approved ADC drugs and drive in-house internal developments for exclusive vaccinations.

Accum can be also employed as an anti-cancer molecule to break down the endosome and rewire mesenchymal stromal cells, converting them from immunosuppressive agents to antigen-presenting cells. Accum comprises a bile acid and a nuclear localization signal, which can be swapped with other relevant molecules to develop new compounds with novel pharmacological characteristics. A distinctive quality of Accum is its ability to manipulate various molecular components like Legos to alter a molecule’s characteristics or add new pharmacological features that would drive problematic cell recycling and drug rejection patterns.

Defence Therapeutics’ creates Accum molecules in various forms because it is excellent at breaking drown endosomal membranes. It can make libraries of Accum and discovers that some of these variations, when added to or injected into tumors, are toxic to cancer cells. One of its Accum variations, the A1, bypasses the drawbacks of protein-based vaccinations by blocking the misaligned degradation of proteins by endosomes to ensure that the antigen is delivered in its natural condition for the proteasome to effectively destroy it.

This is the concept behind the ARM vaccine, a mesenchymal stromal cell (MSC) product pretreated with the A1 admixed with an antigen(s).

“The beauty of Accum is that it can be applied to proteins and genetic material like messenger RNA or DNA, which makes it highly versatile,” says Dr. Moutih Rafei, VP of research and development, Defence Therapeutics.

Defence Therapeutics is also working on a protein-based vaccine to prevent cervical cancer brought on by the HPV virus. The current issue with treating HPV viruses is their ability to mutate into various subtypes that can evade the immune response induced by the Gardasil-9 vaccine. Defence Therapeutics’ vaccine combines Accum and the E7 oncogene protein, a cancer-causing HPV viral byproduct. Unlike Gardasil-9, which solely serves as a preventative measure, this agent can be used therapeutically or prophylactically to cure and prevent cervical cancer. Defence Therapeutics has completed the preclinical work and GLP studies for the vaccine and plans to move onto a phase one trial in 2023 or to license the product to a pharma.

Another Accum molecule slated to reach phase one trial in 2023 is Accutox, which destroys cancer cells by generating DNA damage, immunogenic cell death, and ER stress. It inhibits tumor development paired with immunological checkpoints, showing promising results in treating T-cell lymphoma, melanoma, and breast cancer. In the realm of breast cancer treatment, Defence Therapeutics has a big arm on T-DM1, a crucial ADC in the fight against the disease.

Defence Therapeutics is also evaluating the possibility of launching a veterinary division to provide protein-based vaccinations for farm animals and pets. This pivot highlights the uniqueness of Accum. In this instance, the technology enables the creation of pathogen-derived proteins that can drive the development of vaccines that fight cancer and prevent infectious illnesses like Chlamydia, Lyme disease, or malaria.

Accum is poised to support Defence Therapeutics’ current position as a prominent player in the bio-pharmaceutical landscape by turning ADC challenges into proven platform solutions.