AdAlta announced that AD-214, its treatment candidate for idiopathic pulmonary fibrosis (IPF), had been successfully aerosolized for inhalation – a nebulized form – while maintaining the molecular properties that supported its potential effectiveness in preclinical studies.
“The results of these studies show that AD-214 is administered by inhalation without losing its ability to bind to CXCR4 and at particle sizes with the potential to reach the lungs most severely affected by IPF,” says Tim Oldham , PhD, CEO of AdAlta, said in a Press release.
AD-214 combines two i-bodies or modified antibodies that target the CXCR4 protein. Fibrocytes – cells involved in the development of fibrosis – that express CXCR4 proteins have been shown to be elevated in people with IPF and are an independent predictor of a poorer prognosis.
According to the company AD-214 shown antifibrotic and anti-inflammatory effects in preclinical studies. Additionally, the Anti-CXRC4-i bodies have demonstrated the ability to selectively target diseased lung tissue without affecting healthy tissue.
A phase 1 study confirmed the safety of AD-214 as an intravenous formulation, the company announced in July after studies in non-human primates also showed safety and tolerability. A nebulized form of AD-214 could also reduce treatment costs by allowing for a lower dosage compared to intravenous administration.
The potential effectiveness of AD-214 in nebulized form has been demonstrated in two preclinical studies, AdAlta reported in its press release.
In the first, AD-214 was passed through a microspray device commonly used to spray bleomycin – which induces fibrosis in mice – into the lungs of mice. By administering AD-214 in the same manner, the therapy was observed to reach regions of the lungs where bleomycin induces fibrosis.
Administered by microspray, it was able to bind to its target (CXCR4) even without i-body aggregation or degradation. Efficacy studies of this delivery method in a bleomycin mouse model from IPF are underway and initial results are expected early next year.
The second study looked at AD-214 administered using two commercially available nebulizers that are suitable for the patient. The particle size of the aerosolized drug and the fine dust content (particles smaller than 5 micrometers in diameter) – both important parameters for inhalative therapy – were evaluated. The dose fraction deposited in different lung regions was also simulated with the independent model of the International Commission on Radiological Protection (ICRP), which enables substances that could potentially reach the lungs to be tracked.
The aim of AdAlta was that the nebulizers have a fine dust content of more than 50% and a deposit of more than 10% in the alveoli – the air sacs responsible for the gas exchange in the lungs – or small airways, both areas that are responsible for the IPF treatment are important.
The company reported that the first nebulizer based on the ICRP simulation produced a 55% particulate matter fraction and 46% deposition in the alveolar area of ââthe lungs. The second nebulizer produced a 60% fine particle fraction and 17% deposition in the alveolar area.
These data suggest that AD-214 can be successfully nebulized and reach lung regions required for IPF treatment.
“Simulations of the dose deposited in these regions exceeded our initial expectations,” said Oldham. “These results give us even greater confidence that we can deliver an inhaled formulation in time for planned future clinical trials.”