Industry-leading biotechnology pioneer Defence Therapeutics details how the company is advancing immune oncology through its revolutionary Accum® technology.
Whether using an antibody, cell-based vaccine or small molecule therapeutics, the common denominator in Defence’s development products is the Accum® technology, a platform specifically designed to strategically enhance and increase the efficacy of any existing bio-drug against cancer.
This Accum® technology can be exploited to design a multitude of products, including:
- Antibody-drug conjugates (ADCs);
- Protein/cellular vaccines; and
- Anti-cancer small chemotypes.
The Accum®-ADC program
ADCs were initially made to target breast cancer. The treatment regimens used with these ADCs usually require large doses, while the therapeutic response is limited or weak. By bio-conjugating ADCs with Accum®, Defence Therapeutics has demonstrated improved potency of commercially available ADCs by 20 to 100 folds.
Although Defence is using this approach to optimise commercially available ADCs such as Enhertu®, the company is actively developing two in-house ADCs using its proprietary monoclonal antibodies targeting two tumour-specific cell surface proteins and payloads.
In addition, Defence is partnering with Orano, a world-renowned multinational company, to develop the next-generation radio-immunoconjugates using Defence’s intracellular targeting Accum® technology to provide distinctive best-in-class ADC therapies.
Protein- and cell-based vaccines targeting cancer
Although ADCs represent great tools to attack and kill cancer cells directly, they are ideal against many types of cancer and cannot trigger a long-lasting memory response. This forms the basis of Defence’s vaccine program.
Defence engineered and tested a dual-acting vaccine targeting cervical cancer. In this context, the term “dual” refers to the vaccine’s ability to protect and/or treat established cervical (or head and neck – also induced by HPV) cancer.
This protein-based vaccine is based on using a single protein (in contrast to a mix of nine viral-derived capsid proteins). In preclinical models, Defence demonstrated that the vaccine synergises with various immune-checkpoint blockers, resulting in a survival rate between 70 and 100%.
With the completion of all GLP studies, Defence is actively working to manufacture the vaccine to initiate a Phase I clinical trial against head and neck cancer in 2024, either by itself or in partnership.
Another successful Defence vaccine example demonstrating yet again the versatility of the Accum® technology is the design of the ARM vaccine, relying on the use of a type of stem cell pharmacologically re-programmed to behave as antigen-presenting cells.
This universal, off-the-shelf vaccine has shown impressive cure rates (80-100%) in solid T-cell lymphoma and melanoma models. In parallel to its manufacturing for the Phase I clinical trial targeted in Q1 of 2024, Defence is currently testing the vaccine against two hard-to-treat diseases: pancreatic and ovarian cancer.
What makes the ARM vaccine special could be summarised in twofold: its impressive therapeutic potency and its adaptability to treat any solid or liquid tumour granted access to patient-tumour samples.
The AccuTOXTM program: a new line of anti-cancer therapeutics
Although the goal of using Accum® technology has been mostly to improve biomolecule accumulation in target cells, the Defence team discovered that delivery of unconjugated Accum® or its derivatives can exert potent anti-cancer properties.
This observation gave rise to the AccuTOXTM moiety, a lead Accum® variant capable of halting pre-established lymphoma, melanoma and cervical cancer when given with different immune-checkpoint blockers.
More specifically, the AccuTOXTM was shown to cause DNA damage and trigger a form of immunogenic cell death capable of activating the immune system in parallel. AccuTOXTM destroys tumour cells inside-out and stimulates an immune response to protect the host from subsequent tumour re-growth.
With manufacturing fully completed, IND filing is expected in Q4 of 2023 to start a Phase I clinical trial against a basket of solid tumours at City of Hope National Medical Center and Beckman Research Institute.
Defence Therapeutics is on the verge of critical inflexion points. Its pipeline is well positioned to prevent cancer and/or enhance the efficacy of any bio-drug designed to target cancer.
With all these products and an active program on mRNA cancer vaccines, Defence is in a strong position to truly make a difference in helping reduce cancer death rates. Defence is focussing and dedicating its leadership against one of the biggest enemies of humanity: cancer.
