Defence Therapeutics Inc. updated its stakeholders on its completed achievements as well as outlining the future milestones set for 2023. Over the last three years, Defence has been heavily active in developing its AccumTM-based platform pipeline. The Defence team's strategy and priority is to prove and exploit the versatility of the AccumTM technology demonstrating that it can be used in multiple verticals including: i) the development of a cell- based anti-cancer vaccine targeting solid tumors, ii) the use of AccuTOXTM, a small variant molecule derived from AccumTM backbone, as an anti-cancer injectable for solid tumors, iii) the design of an intranasal AccuTOXTM formulation to treat lung cancer using a non-invasive approach, iv) the development of a protein-based anti-cervical cancer vaccine with dual functions (prophylactic and therapeutic), v) advancing breast-cancer specific antibody-drug conjugate (ADC) program with the goal to initiate a GLP study, and finally vi) investigating the boosting potency of AccumTM applied to the mRNA vaccination platform.

The work conducted on each of the listed program's below are briefly described with much more news and updates to be released as development and advancement takes place. The Company will also entertain and evaluate the possibilities of partnerships, licensing of the technology and strategic joint development opportunities. Defence used a variant of the AccumTM (the A1) to reprogram innate mesenchymal stromal cells into antigen presenting cells.

This "off-the-shelf" universal vaccine (e.g. allogeneic to the recipient) is capable of curing animals with pre-established lymphoma and melanoma, and the observed therapeutic effects synergised with the use of the anti-PD-1 immune-checkpoint blocker. The vaccinated animals survived, and the great majority rejected the established tumour and remained tumour-free for over 3 months. Defence initiated the manufacturing of its ARM vaccine in First Quarter of 2023 with the objective to start treating patients with solid tumors in a Phase I clinical trial by Fourth Quarter of 2023.

Cancer can be generally described as a state of uncontrolled cell proliferation. This is mainly due to losses in the ability of a given cell to activate its own cell death via a specific set of proteins known to sense unusual activities. Although it is difficult to reactivate these specific pathways to elicit cancer cell death, AccuTOXTM can address this challenge.

AccuTOXTM, an AccumTM variant, can control cancer growth when injected directly in tumors. The use of AccuTOXTM in combination with multiple immune- checkpoints results in a survival rate ranging between 60% and 100%, based on the pre-clinical tumor models studied in mice. As for the AccuTOXTM mode of action, a non-biased transcriptomic analysis revealed that the compound impairs pathways crucial to cellular function including DNA replication, cell division, nuclear integrity, and multiple modifications affecting DNA activity.

The accumulation of exhaustive cell repair mechanisms triggered by AccuTOXTM combined to the build-up of misfolded proteins and generation of free radicals induce irreversible DNA damages leading to a general collapse in several cellular pathways resulting in effective cancer cell death. The Defence team completed all preclinical and GLP studies related to the AccuTOXTM molecule as an injectable for solid tumors. The results showed that the drug can halt tumor growth and synergize with multiple immune-checkpoint inhibitors.

Defence also demonstrated, in GLP toxicity studies, that the compound is safe and well tolerated using both rodents and canine animal models. Defence is currently working with City of Hope (Los Angeles, CA, USA) to prepare the IND package filing to initiate a Phase I clinical trial in melanoma patients. The previous success obtained with AccuTOXTM prompt the company to test an intranasal formulation in animals with pre-established lung cancer.

Following completion of MTD studies to identify the best dosing regimen, AccuTOXTM administration was shown to decrease by over 50% the number of cancer nodules especially when combined with the anti-PD1 immune-checkpoint inhibitor. Defence is currently working with a US-based company to identify the best medical device for its AccuTOXTM delivery. GLP tox studies in dogs and rats has begun with the objective of measuring the safety of the formulation using a medical spray device.

This milestone shall be followed by IND package filing to obtain approval for initiating a Phase I clinical trial against lung cancer. By demonstrating great safety and tolerability profiles in patients, AccuTOXTM can become the next generation anti-cancer treatment for a wide range of indications. Cervical cancer is caused by the human papillomavirus (HPV), a sexually transmitted infection.

Following epithelial cell exposure to this virus, various viral-derived proteins initiate a series of transformational events leading to cell immortalization and tumor development. Despite efforts used to reduce cervical cancer prevalence, there is currently no cure for this cancer besides standard of care (surgery). Defence used its proprietary AccumTM platform to engineer the AccuVAC-PT007, a protein-based vaccine targeting the E7 oncoprotein of the HPV virus.

Defence's AccuVAC-PT007 provides complete protection against cervical cancer (prophylactic vaccination) despite multiple challenges. The vaccine was also effective at controlling pre-established cervical cancer growth, which was further amplified when combined with various immune-checkpoint inhibitors. For instance, AccuVAC-PT007 leads to 70% survival in rodents when used with either anti-PD-1 or anti-CTLA4.

The use of the anti-CD47 antibody, a blocker of cancer-mediated inhibition of efferocytosis by phagocytic cell, amplifies the anti- tumoral response boosting survival to 100%. Defence completed GLP studies on rodents and is currently looking to either begin a Phase I clinical trial by its own or to establish a partnership with a Pharma for this program to initiate a Phase I clinical trial.