Clinical stage drug discovery company AdAlta Limited (ASX:1AD) has received positive results from dose simulation studies which support the potential efficacy of AD-214 in fibrotic disease at planned Phase II doses.
The simulations also highlight the possibility that AD-214 could be delivered subcutaneously at lower doses, further enhancing the potential of the product.
These simulations have resulted in two very important conclusions for AdAlta. Firstly, based on our target product characteristics for commercial success, the target dosing regimen for AD-214 has been 10 mg/kg IV every two weeks. The simulations further strengthen and support the potential efficacy of this dosing regimen,” CEO and Managing Director, Dr Tim Oldham, said.
“Secondly, we have, for the first time, been able to explore the potential efficacy of subcutaneously administered AD-214 under clinically convenient dosing regimens. While it still makes sense to move forward to Phase II studies using intravenous AD-214, these subcutaneous results add significant value to our partnering program by pointing the way to a lower cost product in a more convenient format that patients could self-administer at home.
“Our potential partners are genuinely excited by this method of delivery.”
Developing models of drug bioavailability (pharmacokinetics or PK) and target receptor engagement or occupancy (pharmacodynamics or PD) is a valuable tool to assist in selecting doses and dose regimens for clinical trials.
In collaboration with PK/PD modelling experts, Lyo-X, AdAlta has been able to develop a model of AD-214 bioavailability that can accurately reproduce the PK and receptor occupancy profiles observed in Phase I clinical studies.
Drug dosing regimens are selected to maintain a drug concentration and receptor occupancy level, necessary to materially inhibit the progression of disease. Recent AdAlta studies1 showed that AD-214 receptor occupancy as low as 30% could materially inhibit a key fibrotic process (immune and inflammatory cell migration). AD-214 maximally inhibited immune and inflammatory cell migration at receptor occupancy of 60-85%.
Using these findings, the PK/PD model can be used to assess the likely efficacy of different dosing regimens for AD-214.
Next steps
The results reported here reinforce the target IV product profile that AdAlta, in consultation with its advisers, plans to continue through the current Phase I extension study and then into Phase II (with partners).
The results also provide encouragement that an enhanced SC product profile is achievable. Additional product development would be required to confirm these findings and develop a subcutaneous form of AD-214 suitable for clinical use.
Based on the positive response from pharmaceutical companies with whom AdAlta has been able to share these findings, the company believes that a partner could potentially prepare a SC formulation of AD-214 ready for introduction into Phase III clinical trials.
