AdAlta Ltd (ASX:1AD) has released new data providing promising evidence for the effective use of AD-214 in treating patients with Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases.
New data from a Phase 1 human clinical trial suggests that AD-214 administered intravenously every two weeks or less could be effective, offering patients hope for more convenient treatment options.
Critically important data
AdAlta managing director Dr. Tim Oldham emphasised the significance of the new findings, saying: “We have known AD-214 is efficacious in animal models of fibrotic diseases and also that it can at least partially block its target receptor for several days and even weeks after a single IV infusion.
“What we have not known is whether we could replicate the therapeutic effect seen in animals at these levels of receptor occupancy and hence, at dosing frequencies acceptable in humans.”
The study demonstrated that AD-214 could inhibit a key fibrotic process with as little as 60% receptor occupancy, and showed meaningful inhibition at much lower levels.
Improving confidence
The findings also provide valuable insights for determining the appropriate dosing for the next phase of study.
“Linking a clinically measurable parameter (receptor occupancy) with efficacy answers a question commonly asked by potential commercial partners and substantially reduces the risk of Phase 2 studies,” Oldham said.
“The completion of these difficult experiments is a credit to our inhouse scientific team.”
Clinically safe for animals, healthy volunteers
AD-214 is being developed by AdAlta as a first-in-class treatment for fibrotic diseases, including IPF.
It targets and blocks a receptor called CXCR4, which plays a crucial role in various cellular processes involved in fibrosis.
Previous pre-clinical studies demonstrated the efficacy of AD-214 in animal models of lung, kidney and eye fibrosis.
Additionally, the Phase 1 clinical study confirmed its safety and tolerability in healthy volunteers.
Direct evidence
The new data shows that AD-214's ability to occupy CXCR4 receptors and inhibit cell migration, a key fibrotic process, can be replicated at low concentrations observed in the blood days after intravenous infusion.
Notably, even when receptor occupancy was less than 100%, significant inhibition of cell migration was observed.
This groundbreaking study is the first to link receptor occupancy, a clinically measurable parameter, with cell migration.
The upcoming Phase 1 extension study and pharmacokinetic simulation studies will further optimise dosage and dose scheduling to improve the confidence and de-risk the second phase of study.