Aplagon, a Helsinki-based clinical-stage biotechnology company developing novel treatments for thrombo-inflammatory diseases, has announced that the first patient has been dosed in its Phase IIa ‘HEALING’ clinical trial evaluating APAC in patients with Peripheral Arterial Occlusive Disease (PAOD) leading to Chronic Limb?Threatening Ischemia (CLTI).

The trial, currently being conducted in Finland, will evaluate both single-dose and repeat-dose intravenous administration of APAC in up to 42 patients across four study cohorts. The study aims to assess the therapy’s safety and preliminary efficacy in CLTI patients, including those who have undergone revascularisation procedures, as well as its impact on thrombo-inflammatory biomarkers.

CLTI is a severe form of PAOD caused by atherosclerosis-related thrombo-inflammation that restricts blood flow to the limbs. The condition significantly increases the risk of amputation and carries a mortality rate of around 25 percent within the first year. Major risk factors include diabetes and cigarette smoking.

The Phase IIa trial follows approval from Finnish Medicines Agency (FIMEA) after the successful completion of a Phase I international clinical study involving 30 healthy participants. That earlier trial demonstrated that APAC was well tolerated and produced dose-dependent, transient antithrombotic effects.

APAC is a heparin proteoglycan mimetic designed to mimic naturally occurring mast cell-derived molecules. The therapy works by targeting vascular injury sites and providing antiplatelet, anticoagulant and anti-inflammatory effects directly at the damaged blood vessel areas.

According to Aki Prihti, the dosing of the first patient marks an important milestone for the company’s clinical development programme. He noted that the therapy’s targeting ability and retention at vascular injury sites could support broader applications across multiple thrombo-inflammatory vascular diseases.

Maarit Venermo from Helsinki University Hospital said the study aims to improve treatment outcomes for patients with advanced PAOD and CLTI. Previous research suggests that APAC may prevent platelet aggregation and blood clot formation while also reducing inflammation in tissues affected by oxygen deprivation.

PAOD is a progressive condition often caused by atherosclerotic plaque formation that narrows arteries and reduces blood supply to the limbs. While revascularisation procedures can restore blood flow, restenosis occurs in roughly one-third of treated arteries, even when patients receive antithrombotic medication according to existing treatment guidelines.

In addition to the CLTI programme, Aplagon is preparing to launch another Phase II clinical trial in 2026 to evaluate APAC for the prevention of Arteriovenous Fistula (AVF) maturation failure in patients requiring haemodialysis for end-stage kidney disease. Earlier Phase I results in AVF patients showed encouraging early maturation outcomes without safety concerns.

APAC technology is based on research into mast cell-derived heparin proteoglycans conducted by scientists at the Wihuri Research Institute in Helsinki. The therapy is designed for hospital use and can be administered either locally or through intravenous infusion.