Defence Therapeutics Inc. announced the start of its GLP studies on a new intranasal AccuTOXTM formulation. This milestone is crucial to initiate a Phase I trial for this drug in the context of lung cancer. The AccuTOXTM molecule can eradicate cancer cells via different mechanisms including the initiation of immunogenic cells death, endoplasmic reticulum stress and by causing direct damages to DNA.

When tested in three different animal models of solid tumors (lymphoma, melanoma and breast), the compound-controlled tumor growth and synergized with different commercially-used immune- checkpoints (anti-PD-1, anti-CTLA4 and anti-CD47). Building upon this success, Defence designed a new non-invasive formulation allowing the drug to be delivered intranasally to reach lung-established tumors. Lung cancer is the deadliest cancer worldwide, accounting for 1.79 million deaths in 2020.

For that purpose, a series of maximum tolerated dose (MTD) studies were conducted to identify the best regimen for intranasal AccuTOXTM delivery. These studies showed that AccuTOXTM is well tolerated up to 3 mg/kg (5-6 times lower than the injectable dose) and could be delivered up to 6 times over a period of 2 weeks. The translation of this dosing regimen to mice with lung cancer decreased by over 50% the number of cancer nodules when delivered as a combo with the anti-PD1 immune-checkpoint inhibitor.

The next step is now to test the safety and the tolerability of the intranasal Defence's AccuTOXTM formulation in a series of GLP tox studies prior to its therapeutic use on patients in clinical trial. Defence signed a service agreement with Adgyl Life Sciences, a leading Good Laboratory Practice Drug Development and Toxicology Contract Research Organization, to test its intranasal AccuTOXTM formulation using a medical spray device. The studies will be conduct in both rats and dogs.

More specifically, Defence intends to: i) assess the eye irritation potential of AccuTOXTM using reconstructed human cornea-like epithelium, ii) evaluate the skin corrosion potential of AccuTOXTM, iii) determine the plasma PK and bioavailability of AccuTOXTM following a single dose intranasal administration in rats and dogs, iv) determine the toxicity potential and kinetics of AccuTOXTM when administered on alternate days for 7 days (Days 1, 3, 5 and 7) as intranasal drops or intranasal spray (using a spray device) in rats and dogs, and finally v) evaluate multiple parameters such as food consumption, body weight, hematological parameters and histopathology in rats and dogs.