Monocytes for Peripheral Arterial Disease: A Phase 1b/2a trial to treat intermittent claudication

Peripheral arterial disease (PAD) is a common circulatory condition that affects over 200 million people worldwide, especially those over the age of 50. It reduces blood flow to the legs, often causing pain during walking - a condition known as intermittent claudication (IC). While medications, lifestyle changes, and supervised exercise programmes can help, up to 30% of patients do not improve and remain at risk of worsening symptoms, progression to limb threatening ischaemia, and eventual limb amputation. Invasive limb revascularisation by bypass surgery/angioplasty/stenting is costly and associated with complications that include limb loss. There is demand, in the UK and internationally, for developing regenerative treatments for patients with IC to address this area of unmet clinical need and reduce the burden on health services. The challenge the project addresses Current treatments for IC do not effectively reverse the underlying arterial insufficiency and invasive options are not routinely recommended due to their risk profile and poor long-term durability. There are no approved therapies that stimulate clinically effective vascular remodelling or prevent progression to chronic limb-threatening ischaemia (CLTI). The key challenge is to develop a safe, scalable and disease-modifying therapy that promotes natural blood vessel regeneration in patients who have exhausted standard medical therapy. Aims and objectives This project will evaluate MON002, an autologous cell therapy using monocytes which are primed with clinical-grade mesenchymal stem cells towards a vascular remodelling functional phenotype, in a first-in-kind Phase 1b/2a clinical trial in patients with IC. The specific objectives are to: Scale up GMP manufacturing of MON002 - leukapheresis-isolated monocytes from patients, engineered to express a pro-angio/arteriogenic phenotype by co-culture with mesenchymal stem cells; Test the safety, tolerability, and optimal dosing of MON002 with an adaptive, randomised, placebo-controlled trial in patients with IC; Assess early signals of efficacy including 6-minute walking distance, blood flow (ankle:brachial pressure index; ABPI), quality of life, and relevant biological markers; Engage with regulatory bodies to define a clear path towards later-phase trials and clinical use. Potential applications and benefits If successful, MON002 could offer the first regenerative, minimally invasive treatment for patients with intermittent claudication - an intervention that will help patients regain mobility, reduce symptoms, prevent progression to CLTI and avoid major surgery or future amputation. It may reduce hospital admissions and healthcare costs, while enhancing patient quality of life. The platform also has broader relevance to other conditions involving ischaemic tissues, including the ischaemic myocardium. In the longer term, MON002 could help integrate cell-based therapies into routine vascular care, contributing to the UK's ambition of becoming a global leader in advanced cell and gene therapies.