Australian pharmaceutical company Amplia Therapeutics (ASX: ATX) has received new data from a recent phase 1 clinical trial, which demonstrates the ability of lead drug AMP945 to inhibit focal adhesion kinase (FAK) in healthy human volunteers when given as an oral capsule.
Conducted at Nucleus Network in Melbourne, the trial aimed to establish the safety, tolerability and pharmacokinetics of AMP945 by evaluating the nature, incidence and severity of adverse events, withdrawals, physical examinations, vital signs, electrocardiograms (ECGs) and lab test results including assessment of biochemical and haematological markers.
Skin biopsies were collected from 56 healthy volunteers who had been dosed with single or multiple doses of AMP945 (up to 125 milligrams and 100mg respectively) or a placebo, to evaluate the drug’s ability to inhibit FAK in human tissue.
One cohort of participants was given AMP945 before and after eating in order to study the effect of food on absorption of the drug.
Analysis of the samples required Amplia to develop a sensitive assay which allowed the measurement of the active form of FAK (phospho-FAK or pFAK) in skin samples before and after the drug was administered.
The results demonstrated that oral administration of AMP945 can result in a decrease in active pFAK and the extent of the FAK inhibition correlates with drug levels.
The data will be used to further refine AMP945 dosage levels for a phase 2 clinical trial in patients with pancreatic cancer.
It will also provide guidance for an investigation into AMP945 on pulmonary fibrosis planned for the late-2022.
Next stage of trials
Amplia chief scientific officer Dr Mark Devlin was pleased the phase 1 data could support the next stage of clinical trials and said the new assay had been verified as a test method to guide dose selection.
“We have observed inhibition of FAK by AMP945 in animal models and this has been associated with anti-tumour and anti-fibrotic activity … being able to observe [the same response] in human volunteers is an important piece of the jigsaw,” he said.
“Getting such clear and compelling FAK inhibition data in our phase 1 trial is very pleasing and provides additional comfort as we start trialling AMP945 in patients.”
Dr Devlin said a review of primary, secondary and exploratory endpoints for the phase 1 trial confirmed the drug was safe and well-tolerated at all doses tested.
It also exhibited “excellent pharmacokinetic properties” making it suitable for once-daily oral dosing, and was able to engage with its intended FAK target.