Potential IPF Treatment AD-214 Works in Inhaled Form, AdAlta Says

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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AdAlta announced that AD-214, its candidate treatment for idiopathic pulmonary fibrosis (IPF), has been successfully made into an aerosol for inhalation — a nebulized form — while retaining the molecular properties that supported its potential effectiveness in preclinical studies.

“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,” Tim Oldham, PhD, CEO of AdAlta, said in a press release.

AD-214 combines two i-bodies, or modified antibodies, that target the protein CXCR4. Fibrocytes — cells involved in fibrosis development — expressing CXCR4 proteins have been shown to be increased in people with IPF and are an independent predictor of worse prognosis.

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According to the company, AD-214 demonstrated anti-fibrotic and anti-inflammatory activity in preclinical studies. Additionally, the anti-CXRC4 i-bodies have shown an ability to selectively target diseased lung tissue without affecting healthy tissue.

A Phase 1 trial supported the safety of AD-214 given as an intravenous formulation, the company announced in July, following studies in nonhuman primates that also showed safety and tolerability. A nebulized form of AD-214 might also lower the treatment’s cost by allowing for lower dosing relative to intravenous administration.

AD-214’s potential effectiveness in a nebulized form was demonstrated in two preclinical studies, AdAlta reported in its release.

In the first, AD-214 was passed through a microspray device commonly used to spray bleomycin — which induces fibrosis in mice — into mouse lungs. By administering the AD-214 in the same manner, the therapy was seen to reach lung regions where bleomycin induces fibrosis.

Given by microspray, it was also able bind to its target (CXCR4) without i-body aggregation or degradation. Efficacy studies of this delivery method in a bleomycin mouse model of IPF are currently underway and initial results are expected early next year.

The second study evaluated AD-214 administered using two commercially available nebulizers suitable for patient use. The particle size of the aerosolized medication and the fine particle fraction (particles less than 5 micrometers in diameter) — both important measures for inhaled therapies — were assessed. The dose fraction deposited in different lung regions was also simulated using the independent International Commission of Radiological Protection (ICRP) model, which allows for tracking substances that can potentially enter the lungs.

AdAlta’s goal was for the nebulizers to show a greater than 50% fine particle fraction and greater than 10% deposition in the alveoli — the airs sacs responsible for gas exchange in the lungs — or small airways, both regions important in IPF treatment.

The company reported that first nebulizer produced a 55% fine particle fraction and 46% deposition in the alveolar region of the lung based on the ICRP simulation. The second nebulizer produced a 60% fine particle fraction and 17% deposition in the alveolar region.

These data suggest that AD-214 can be successfully nebulized and reach lung regions necessary for IPF treatment.

“Simulations of the dose deposited in these regions exceeded our initial expectations,” Oldham said. “These results give us even greater confidence that we can deliver an inhaled formulation in time for scheduled future clinical studies.”

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