AdAlta Ltd (ASX:1AD) has finalised its preclinical development program to develop an inhaled version of AD-214, the company’s first-in-class therapeutic for fibrotic diseases including Idiopathic Pulmonary Fibrosis (IPF) and other Interstitial Lung Diseases (ILDs).
Notably, the clinical-stage biotech company has initiated a comprehensive package of in vivo and in vitro studies for the development for AD-214.
Looking ahead, work to optimise a formulation of AD-214 for nebulisation and inhalation is expected to be completed in parallel with preclinical studies, enabling large animal toxicology studies to be initiated in the March quarter of next year.
Comprehensive package
AdAlta CEO and managing director Dr Tim Oldham said: “Our team, working with world experts in various fields of inhalation drug delivery, have designed a comprehensive package of preclinical studies to demonstrate that AD-214 can be delivered to the lower airways of the lungs, distributed to fibrotic tissue and can affect the course of fibrosis once there.
“These are complex studies and our team’s approach is to develop a rich body of evidence supporting the potential of inhaled AD-214 that does not critically depend on the results of any individual study.
“As the data becomes available progressively over the next two quarters, inhaled AD-214 will be further de-risked, enabling additional partnering discussions.”
Development plan
AdAlta has now finished mapping out the preclinical development plan for the inhaled formulation of AD-214.
AdAlta’s development plan addresses three questions, covering delivery of the drug, its distribution and retention, and its efficacy:
- Can nebulised AD-214 reach the lower airways of the lungs intact?
- Can AD-214, once in the lower airways of the lungs, reach and be retained in fibrotic tissue?
- Can AD-214 moderate fibrotic disease progression when delivered directly to fibrotic lung tissue?
Moving forward, the ongoing and planned experiments to address these questions are anticipated to produce a steady flow of data between now and when the study wraps in the September quarter.
Studies undertaken
Delivery, distribution and retention will be studied using PET imaging and pathology studies in animals and in vitro-cultured tissue models.
Data from this study has been delayed due to technical difficulties establishing a fibrosis baseline in the first attempt.
Notably, in vivo efficacy studies include the gold standard bleomycin mouse model of IPF.
This will be further complemented by results from studies of AD-214 in animal models of other fibrotic diseases (kidney and eye).
Further, in vivo efficacy studies will be supported by in vitro studies in human lung airway cells and cultured human lung tissue.
Next clinical studies are anticipated to comprise an initial healthy volunteer bridging safety study, which will be combined with IPF patient imaging studies using the already developed radiolabelled (for PET imaging) version of AD-214 ahead of efficacy studies in IPF patients.