In-Vitro evaluation of the effectiveness of a novel Dual Drug Coated Balloon catheter to treat Vascular and cardiovascular diseases

Peripheral arterial disease (PAD) is estimated to affect over 200 million people around the world and this number is increasing continuously. Endovascular interventions with or without stenting are among the preferred treatment choices. Recent randomised controlled clinical trials have demonstrated the superiority of drug-coated balloon (DCB) therapy compared to uncoated balloon, in terms of improved patency. In many clinical cases, DCB devices offer an alternative to Drug-Eluting Stents (DES), while also:

1\. Avoiding a permanent implant

2\. Shorter medications

3\. Avoiding additional/multiple stent layers.

Generally, paclitaxel-DCB are the device of choice, but devices differ in terms of drug dosing, the selection of the excipient and the overall coating formulation. The main challenges in the effectiveness of this approach are the efficient delivery of drug to the target lesion and retention of drug in the vessel wall at therapeutic levels long enough for healing to occur. For current paclitaxel-DCBs, as much as 90% of drug is lost in the blood stream, with only between 1-10% successfully delivered. Furthermore, drug concentration in tissue rapidly drops below the nominal 1ug/ml therapeutic limit. To prevent restenosis and thrombosis, and promote healing, the drugs should be retained in the arterial vessel wall for a minimum of 30-days and, ideally, up to 90-days. Many DCBs on the market rapidly fall below this level as drug is washed into the bloodstream.

While single-drug DCBs utilise one therapeutic, generally to prevent restenosis, vascular healing is a complex multi-stage process, with a different drug required in the latter stages to the early stages of healing.

This unmet need has encouraged Arterius to develop an alternative a novel dual drug DCB using antiproliferative to prevent restenosis in the early stages, and an antithrombotic and promote vascular healing in the later stages. Using Arterius' unique and patented excipient and dual drug formulation, preliminary work has shown good performance delivering drugs to the tissues in ex-vivo and in-vivo models.

The oft-quoted therapeutic limit of 1ug/ml for both paclitaxel and sirolimus does not appear to have sound scientific basis. Understanding the dose-dependent effects of these drugs on the cells of the arterial tissue is essential to achieve effective dosage.

Development of next-generation DCB using this approach would add a significant market opportunity, complimentary to Arterius current bioresorbable vascular stent programmes. It will potentially reduce the risk of amputation and death in peripheral artery disease patients and reduce medication costs for the NHS.