Posted: 13 December 2021
BioMelbourne Network Member, AdAlta Limited, the clinical stage drug discovery company developing novel therapeutic products from its i-body platform, is pleased to announce that initial testing of AD-214 in nebulisation devices has exceeded expectations.
AdAlta is developing a patient-preferred and lower cost inhaled formulation of AD‑214 for future clinical studies in Idiopathic Pulmonary Fibrosis (IPF). An important early step in development is to ensure that AD-214 can be successfully converted to fine droplets or aerosols for penetration to the smaller airways of the lungs, a process called nebulisation. Two studies have now been conducted.
AdAlta’s CEO, Dr Tim Oldham commented:
“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.”
In the first study, undertaken by AdAlta, AD-214 was passed through a microspray device commonly used to administer bleomycin to the lungs of mice (bleomycin is used to induce fibrosis in mice). Administering AD‑214 by the same method is intended to deliver AD‑214 to the regions of bleomycin induced fibrosis. AD‑214 was shown to bind to its target, CXCR4, after passing through the microsprayer without signs of aggregation or degradation. Efficacy studies of AD-214 delivered by microsprayer in a bleomycin mouse model of IPF have now commenced at PharmaLegacy Laboratories (Shanghai) Co Ltd, with initial results expected early in 2022.
In the second study, AD-214 was nebulised in two commercially available nebulisers suitable for human use. The aerosol particle size and fine particle fraction (fraction of particles less than 5 m in diameter) were measured and the fraction of the dose that would be deposited in different regions of the lung was simulated using the independent International Commission of Radiological Protection (ICRP) model. AdAlta’s objective was to ensure nebulisers produced greater than 50% fine particle fraction and greater than 10% deposition in alveolar or small airway, region of the lungs which is important for IPF therapy. The study was conducted by specialist inhalation contract development and manufacturing organisation, Vectura Ltd (UK). Results significantly exceeded expectations.
As previously announced (July 2021), AD-214 has successfully completed Phase I safety studies by intravenous administration and clinical supplies of drug substance for the next clinical trials are scheduled to be available in mid-2023. Pre-clinical PET imaging studies supported development of an inhaled formulation for those trials to improve bioavailability, improve patient convenience and reduce cost (by reducing dose).