Defence Therapeutics Inc., a Canadian biopharmaceutical company specialising in the development of immune-oncology vaccines and drug delivery technologies is pleased to announce the start of its GLP studies on a new intranasal AccuTOXTM formulation. This milestone is crucial in initiating a Phase I trial for this lung cancer drug.
The AccuTOXTM molecule can eradicate cancer cells via different mechanisms including the initiation of the death of immunogenic cells, endoplasmic reticulum stress and by causing direct damage to DNA. When tested in three different animal models of solid tumours (lymphoma, melanoma and breast), the compound-controlled tumour growth synergised with different commercially used immune-checkpoints (anti-PD-1, anti-CTLA4 and anti-CD47).
Building on this success, Defence designed a new non-invasive formulation, allowing the drug to be delivered intranasally, helping it to reach lung-established tumours. Lung cancer is the deadliest cancer worldwide, accounting for 1.79 million deaths in 2020.
Intranasal AccuTOXTM: the past, the present and the future
“Although most of our efficacy studies delivered AccuTOXTM directly into solid tumours, our objective was to find new ways to target other deadly and difficult to treat ailments such as lung cancer” said Dr Rafei, the VP research and development of Defence.
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 was well tolerated up to three mg/kg (five to six times lower than the injectable dose) and could be delivered up to six times over a period of two 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 combination 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.
Next step: GLP studies
Defence have 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 seven days (Days one, three, five and seven) 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, haematological parameters and histopathology in rats and dogs.
“The completion of these GLP tox studies, in parallel to the initiation of a Phase I trial on AccuTOXTM as an injectable for solid tumours, will allow Defence to achieve important infliction points with major milestones to be accomplished in 2023. By demonstrating great safety and tolerability profiles using both AccuTOXTM formulation (injectable and intranasal), Defence is poised to become a leading biotech in the field of immuno-oncology and cancer therapeutics with a lead compound possessing a wide scope of therapeutic applications”, said Mr Plouffe, the CEO of Defence Therapeutics.
The global lung cancer therapeutics market size was estimated at USD 27.57 billion in 2021 and it is expected to surpass around USD 55.6 billion by 2030 with a registered CAGR of 8.11% from 2022 to 2030 according to Precedence Research.
Defence Therapeutics is a publicly-traded biotechnology company working on engineering the next generation vaccines and ADC products using its proprietary platform. The core of Defence Therapeutics platform is the ACCUMTM technology, which enables precision delivery of vaccine antigens or ADCs in their intact form to target cells. As a result, increased efficacy and potency can be reached against catastrophic illness such as cancer and infectious diseases.