AdAlta Ltd (ASX:1AD) has received results of dose simulation studies that support the potential efficacy of its i-body drug candidate AD-214 in fibrotic disease at its planned intravenous dose regime.
The simulations also highlight the possibility that AD-214 could be delivered subcutaneously at lower doses, further enhancing the potential of the product.
Combined, the results of the studies — supporting both the potential efficacy of target intravenous doses of AD-214 and that subcutaneous administration could also be effective — reduce Phase II risk and significantly enhance AdAlta’s partnering potential.
"Two important conclusions"
AdAlta CEO and managing director Tim Oldham said, “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.
“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.”
AD-214
AD-214 has significant anti-fibrotic effects in treating a type of fibrosis of the lung, known as idiopathic pulmonary fibrosis (IPF).
The i-body has also demonstrated to be useful in treating fibrosis of the eye and is being pursued as an additional opportunity for the treatment of age-related macular degeneration (wet-AMD).
AD-214 also has application in other fibrosis indications, including fibrosis diseases of the liver, skin and kidney.
Intravenous (IV) delivery results
Intravenous (IV) delivery involves direct infusion via canula into a vein during a hospital or clinic visit.
The model suggests that a clinically feasible dosing regimen of 10 mg/kg of AD-214 administered IV every two weeks bind its target receptor, CXCR4, and maintains levels of receptor occupancy necessary to materially inhibit a model fibrosis process.
This dosing regimen is being used in the current Phase I extension clinical trial and would likely be progressed in a Phase II clinical trial.
Subcutaneous (SC) delivery results
Subcutaneous (SC) delivery involves administration under the skin via syringe and can be self-administered by patients at home.
The model was used to investigate the feasibility of administering AD-214 subcutaneously, suggesting that target levels of receptor occupancy could be achieved at doses of 1-3 mg/kg weekly and less than 0.1 mg/kg daily.
Not only is SC administration more convenient for the patient, it also requires much less AD-214 (based on the simulations), thus substantially reducing cost of goods.
AdAlta notes that more work is required to verify these results and develop a suitable formulation for subcutaneous use.
Looking ahead
The results reinforce the target IV product profile that will be used through the current Phase I extension study and then into Phase II.
AdAlta says the results also provide encouragement that an enhanced subcutaneous product profile is achievable, although additional product development would be required to confirm these findings and develop a subcutaneous form of AD-214 that’s suitable for clinical use.
Pharmaceutical companies have responded positively to the findings and AdAlta believes that a partner could prepare a subcutaneous formulation of AD-214 ready for introduction into Phase III clinical trials.