AdAlta Limited has finalised the preclinical development program to develop an inhaled version of AD-214, its lead asset. AD-214 is being developed as a first in class therapeutic for fibrotic diseases including Idiopathic Pulmonary Fibrosis (IPF) and other Interstitial Lung Diseases (ILDs). In July 2021, AdAlta announced the successful completion of a Phase I clinical trial assessing the safety and tolerability of AD-214 in healthy volunteers, the securing of production slots to deliver the next batch of clinical grade AD-214 in mid-2023 and that it would use the intervening period to develop a more patient convenient, lower cost inhaled formulation of AD-214.

AdAlta has now finished mapping out the preclinical development plan for the inhaled formulation of AD-214. The development plan addresses three questions: 1. Delivery: can nebulised AD-214 reach the lower airways of the lungs intact? 2. Distribution and retention: can AD-214, once in the lower airways of the lungs, reach and be retained in fibrotic tissue?

3. Efficacy: can AD-214 moderate fibrotic disease progression when delivered directly to fibrotic lung tissue? The ongoing and planned experiments to address these questions are anticipated to produce a steady flow of data between now and completion in the September quarter. Delivery, distribution and retention will be studied using PET imaging and pathology studies in both animal and in vitro cultured tissue models.

In vivo efficacy studies include the gold standard bleomycin mouse model of IPF. Data from this study has been delayed due to technical difficulties establishing a fibrosis baseline in the first attempt. This is not an uncommon issue for studies of this kind.

This study will be repeated without affecting overall timelines. In vivo efficacy studies will be supported by in vitro studies in human lung airway cells and in cultured human lung tissue. They will be further complemented by results from studies of AD-214 in animal models of other fibrotic diseases (kidney and eye).

Work to optimise a formulation of AD-214 for nebulisation and inhalation is expected to be completed in parallel with the preclinical studies, enabling large animal toxicology studies to be initiated in the March quarter of 2023. Assuming success, these will in turn enable the next clinical studies to commence in the second half of 2023 as previously announced. 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.

In delivering this program, AdAlta is leveraging significant global expertise in inhaled drug delivery: Arrangements are being finalised to conduct imaging studies of AD-214 distribution and retention with Allergenix Pty Ltd. (Australia), a preclinical contract research organisation (CRO) specialising in sheep models of pulmonary drug delivery and pulmonary disease including asthma, COPD and fibrosis. Sheep lungs are structurally very similar to human lungs; Dr. Louise Organ, who developed the sheep IPF model and has extensive experience using cultured human lung tissue to model the activity of anti-fibrotic agents, has recently joined the AdAlta team and will lead these studies; Prof Antje Prasse, a world recognised IPF researcher at the Fraunhofer Institute (Germany), has previously shown that AD-114, the i-body incorporated into AD-214, can inhibit the growth of spheroids from cells collected from the lining of the airways in IPF patients, and is now repeating these studies using AD-214; Contracts are being finalised with a new contract research organisation to overcome the technical difficulties associated with establishing fibrosis in the bleomycin mouse model of IPF to further explore distribution, retention and anti-fibrotic effect of AD-214 directly delivered to the lungs; Specialist inhalation contract manufacturing firm, Vectura Ltd. (UK), has been contracted to optimise a formulation of AD-214 for nebulisation and inhalation; ITR Laboratories Canada Inc. (Canada) has been contracted for inhaled toxicology studies.