Periodic Reporting for period 2 - APAC-ON (APAC – the first targeted therapy for peripheral arterial occlusive disease.)
Periodo di rendicontazione: 2023-06-01 al 2025-02-28
Peripheral arterial occlusive disease (PAOD) is a serious chronic cardiovascular condition associated with high mortality, morbidity, and limb amputation rates. PAOD is caused by atherosclerosis, which together with inflammation and thrombosis (blood clot formation) leads to impaired and eventually full occlusion of blood flow to the lower limbs. Funded by the European Innovation Council, the APAC-ON project is introducing a novel drug that uniquely targets these atherosclerotic sites, provides a local, long-term antithrombotic and anti-inflammatory effect, and may inhibit further atherosclerosis. APAC-ON will evaluate the safety and efficacy of the drug in patients with advanced PAOD.
There is a major unmet need for effective and safe therapies for PAOD due to the high cardiovascular burden, including mortality, morbidity, and amputation rates in these patients. Aplagon is developing the first vascular injury -targeting product (APAC) for the local treatment of advanced PAOD. PAOD is caused by fatty deposits in lower limb arteries (atherosclerosis) that become inflamed (thrombo-inflammation), resulting in blood coagulation (atherothrombosis). APAC uniquely targets the sick arteries, prevents further atherosclerosis, and downregulates thrombo-inflammation, the main drivers of PAOD. At the beginning of the EIC-grant project, Aplagon had completed preclinical proof-of-concept and toxicology studies, initiated a Phase 1 clinical study in hemodialysis access failure indication (local administration) and was preparing for clinical studies in advanced PAOD patients (systemic administration). Aplagon has an experienced, international team, and is supported by a renowned scientific advisory board. The EIC-grant project aims to show the safety and preliminary efficacy of APAC in advanced PAOD-patients, a major value inflection point.
There is a major unmet need for effective and safe therapies for PAOD due to the high cardiovascular burden, including mortality, morbidity, and amputation rates in these patients. Aplagon is developing the first vascular injury -targeting product (APAC) for the local treatment of advanced PAOD. PAOD is caused by fatty deposits in lower limb arteries (atherosclerosis) that become inflamed (thrombo-inflammation), resulting in blood coagulation (atherothrombosis). APAC uniquely targets the sick arteries, prevents further atherosclerosis, and downregulates thrombo-inflammation, the main drivers of PAOD. At the beginning of the EIC-grant project, Aplagon had completed preclinical proof-of-concept and toxicology studies, initiated a Phase 1 clinical study in hemodialysis access failure indication (local administration) and was preparing for clinical studies in advanced PAOD patients (systemic administration). Aplagon has an experienced, international team, and is supported by a renowned scientific advisory board. The EIC-grant project aims to show the safety and preliminary efficacy of APAC in advanced PAOD-patients, a major value inflection point.
The main achievements in the project are as follows:
• Aplagon’s team has been strengthened with a Clinical Study Director and a Quality Director
• Clinical batches of APAC have been manufactured, and an improved formulation has been developed and placed in long-term stability studies
• Release of APAC for use in clinical studies in Europe has been organised, and two clinical batches have been released by a Qualified Person (QP) in Europe
• Method development, qualification and validation of zirconium-labelling of APAC have been successfully completed
• Commercial and quality agreements with collaboration partners for the clinical studies in Europe, as well as audits, have been completed
• Clinical Trial Application (CTA) for the PET-imaging study in advanced PAOD patients and healthy subjects (CHASE-study) has been approved
• The first participants have successfully completed the CHASE-study, including three PET-imaging visits
• Scientific Advice has been received from European Medicines Agency (EMA)
• Pricing and market opportunity study have been carried out, and APAC positioning in the PAOD/CLI-indication finetuned
• EUR 7 million funding round was closed. The funding was led by new investors FSG Fund, a Nordic venture capital fund focused on life sciences, and EIC Fund
• The funding enables the initiation of a Phase 2a study in PAOD and its most advanced stage critical limb ischemia (CLI, nowadays often referred to as chronic limb-threatening ischemia, CLTI). The study design is significantly more extensive than originally envisaged
• Phase 1 study in healthy volunteers (systemic administration, CRSC20007), which is not part of the Project but is the prerequisite for the Phase 2a study, has been successfully completed.
• Aplagon’s team has been strengthened with a Clinical Study Director and a Quality Director
• Clinical batches of APAC have been manufactured, and an improved formulation has been developed and placed in long-term stability studies
• Release of APAC for use in clinical studies in Europe has been organised, and two clinical batches have been released by a Qualified Person (QP) in Europe
• Method development, qualification and validation of zirconium-labelling of APAC have been successfully completed
• Commercial and quality agreements with collaboration partners for the clinical studies in Europe, as well as audits, have been completed
• Clinical Trial Application (CTA) for the PET-imaging study in advanced PAOD patients and healthy subjects (CHASE-study) has been approved
• The first participants have successfully completed the CHASE-study, including three PET-imaging visits
• Scientific Advice has been received from European Medicines Agency (EMA)
• Pricing and market opportunity study have been carried out, and APAC positioning in the PAOD/CLI-indication finetuned
• EUR 7 million funding round was closed. The funding was led by new investors FSG Fund, a Nordic venture capital fund focused on life sciences, and EIC Fund
• The funding enables the initiation of a Phase 2a study in PAOD and its most advanced stage critical limb ischemia (CLI, nowadays often referred to as chronic limb-threatening ischemia, CLTI). The study design is significantly more extensive than originally envisaged
• Phase 1 study in healthy volunteers (systemic administration, CRSC20007), which is not part of the Project but is the prerequisite for the Phase 2a study, has been successfully completed.
Aplagon’s solution has the potential to provide a novel way of treating PAOD/CLI-patients and thereby become a breakthrough therapy in PAOD/CLI and other thrombo-inflammatory diseases. As an affordable and efficacious therapy, APAC is expected to reduce the need for revascularisations, lower limb amputations and hospitalisations.
In PAOD indication, APAC is initially targeted to the most advanced patients, CLI patients, undergoing endovascular revascularisation (balloon angioplasty). APAC uniquely targets the vascular injury sites (caused by atherosclerosis and revascularisation), regulates the platelet activity, coagulation, and inflammation at these sites, and supports the physiological vessel wall healing. These APAC properties impact the underlying causes of PAOD/CLI progression and poor outcomes in CLI revascularisations. No other therapy has similar mechanism of action, targets the critical blood-vessel wall interactions, or provides local, long-term effect at the vascular injury sites.
The results generated in the Project support APAC’s local long-term effect, and thereby the intended use in CLI-patients in connection with revascularisations. The Project has also enabled the initiation of a larger Phase 2a PAOD/CLI-study than originally intended, including both revascularisation and non-revascularisation groups, enabling faster progress to late-stage clinical studies. The study will also provide the basis for potentially expanding the use of APAC to other thrombo-inflammatory indications in the future, as many of the biomarkers studied are relevant in many severe, hospital-based cardiovascular indications. Aplagon and APAC have the potential to significantly strengthen the pharmaceutical industry and technology base in Europe by providing a breakthrough therapy for PAOD/CLI and potentially also to other hospital-based cardiovascular indications.
In PAOD indication, APAC is initially targeted to the most advanced patients, CLI patients, undergoing endovascular revascularisation (balloon angioplasty). APAC uniquely targets the vascular injury sites (caused by atherosclerosis and revascularisation), regulates the platelet activity, coagulation, and inflammation at these sites, and supports the physiological vessel wall healing. These APAC properties impact the underlying causes of PAOD/CLI progression and poor outcomes in CLI revascularisations. No other therapy has similar mechanism of action, targets the critical blood-vessel wall interactions, or provides local, long-term effect at the vascular injury sites.
The results generated in the Project support APAC’s local long-term effect, and thereby the intended use in CLI-patients in connection with revascularisations. The Project has also enabled the initiation of a larger Phase 2a PAOD/CLI-study than originally intended, including both revascularisation and non-revascularisation groups, enabling faster progress to late-stage clinical studies. The study will also provide the basis for potentially expanding the use of APAC to other thrombo-inflammatory indications in the future, as many of the biomarkers studied are relevant in many severe, hospital-based cardiovascular indications. Aplagon and APAC have the potential to significantly strengthen the pharmaceutical industry and technology base in Europe by providing a breakthrough therapy for PAOD/CLI and potentially also to other hospital-based cardiovascular indications.