ESOC 2025 | A Phase I trial of a novel matrix metalloproteinase broad-spectrum inhibitor after ischemic stroke

Yes I’m working with this company from Poland that has repurposed a previously oncology drug, marimastat, and re-engineered it pharmacologically, repurposed it I should say, for use in stroke neuroprotection. It’s now called PKL012 if I’m recalling that correctly and the molecule is a broad-spectrum metalloproteinase, matrix metalloproteinase inhibitor. It has actions against many of the matrix metalloproteinases which are involved in ischemic stroke, especially in hemorrhagic transformation, and this drug inhibits them quite strongly and in animal models has shown benefit in ischemic stroke. This particular study is a Phase I study in normal volunteers where the company implemented a single dose and a multiple dose regimen to look at the pharmacokinetics. They also had a secondary aim of looking at safety and tolerability, and what we found was that both the single dose and the multiple doses achieved an excellent concentration area under the curve in healthy volunteers, and the single dose has a very favorable pharmacokinetics where the drug is eliminated after two days completely. There is no accumulation. I’m sorry, in the multiple dosing, we did not find any accumulation after the last dose, which was given for a week. The drug then is eliminated over the next few days completely. The tolerability and safety were excellent. There were no serious adverse events. So it’s a first step towards a progression to now looking at efficacy and more robust safety or early efficacy and more robust safety in a Phase II study. Really, the pharmacokinetics were important to work out. It’s an oral neuroprotectant, and so it can be given easily after ischemic stroke in order to achieve neuroprotection. So very happy with the results and looking to progress to the next step based on these very promising results.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.