AdAlta Ltd (ASX:1AD) has achieved an important milestone in developing its novel therapeutic product AD-324 from its i-body platform, with initial testing of AD-214 nebulisation devices exceeding expectations.
The company is developing AD-214 into a patient-preferred, low-cost inhaled formulation for future clinical studies in Idiopathic Pulmonary Fibrosis (IPF).
Ensuring that AD-214 can be converted into fine droplets or aerosols (nebulisation) for penetration into the smaller airways of the lungs is an important early step in development. Two studies have now been conducted.
“Exceeded initial expectations”
AdAlta CEO Dr Tim Oldham said: "The results of these studies support AD-214 being delivered by inhalation without losing its ability to bind to CXCR4 and at particle sizes with potential to travel to the furthest reaches of the lungs that are most affected by IPF.
“Simulations of the dose deposited in these regions exceeded our initial expectations. These results give us even greater confidence that we can deliver an inhaled formulation in time for scheduled future clinical studies.”
The first study involved passing AD-214 through a micro-spray device commonly used to administer compounds to the lungs of mice. Usually used to administer bleomycin - which induces fibrosis in mice - the same method effectively delivered AD-214 to the regions of the lungs with bleomycin-induced fibrosis.
AD-214 was shown to bind to its target, CXCR4, after passing through the micro-sprayer without signs of aggregation or degradation.
Efficacy studies of AD-214 delivered by micro-sprayer in a bleomycin mouse model of IPF have now commenced at PharmaLegacy Laboratories (Shanghai) Co Ltd with initial results expected early in 2022.
The second study involved nebulising AD-214 with two commercially available nebulisers suitable for human use. The aerosol particle size and fine particle fraction (fraction of particles less than 5 micrometres in diameter) were measured.
The study then simulated the fraction of the dose that would be deposited in different regions of the lung using the independent International Commission of Radiological Protection (ICRP) model.
Study results
AdAlta’s objective was to ensure nebulisers produced greater than 50% fine particle fraction and greater than 10% deposition in alveolar or small airway, a region of the lungs that is important for IPF therapy.
The study was conducted by specialist inhalation contract development and manufacturing organisation, Vectura Ltd (UK).
Results significantly exceeded expectations:
Additionally, AD-214 has successfully completed Phase I safety studies by intravenous administration. Clinical supplies of the drug for the next clinical trial are scheduled to be available in mid-2023.
Pre-clinical PET imaging studies will support the development of an inhaled formulation for those trials to improve bioavailability, improve patient convenience and reduce cost (by reducing dose).
About AdAlta
AdAlta Limited is a clinical-stage drug development company headquartered in Melbourne, Australia.
The company is using its proprietary i-body technology platform to solve challenging drug targeting problems and generate a promising new class of single domain antibody protein therapeutics with the potential to treat some of today’s most challenging medical conditions.
The i-body technology mimics the shape and stability of a unique and versatile antigen binding domain that was discovered initially in sharks and then developed as a human protein.
The result is a range of unique proteins capable of interacting with high selectivity, specificity and affinity with previously difficult to access targets such as G-protein coupled receptors (GPCRs) that are implicated in many serious diseases.
i-bodies are the first fully human single domain antibody scaffold and the first based on the shark motif to reach clinical trials.