A systematic review of more than two decades of clinical data has found no evidence of increased cancer or retinal safety risks from therapies designed to promote blood vessel growth.

Review examines long-standing safety concerns

New data presented at the European Society of Cardiology Congress 2026 could support renewed development of therapies designed to promote blood vessel growth in people with coronary artery disease (CAD).

The systematic review assessed 11 clinical studies of pro-angiogenic growth factor approaches conducted between 2002 and 2024, involving 636 patients with angina or peripheral artery disease. The studies included 441 patients who received pro-angiogenic treatment and 195 who received placebo, with follow-up ranging from two to 12 years.

The analysis found no evidence of additional long-term safety risks associated with pro-angiogenic interventions, including VEGF-A isoforms, compared with placebo or age-matched populations.

Mean malignancy incidence was similar between the pro-angiogenic and placebo groups, at 0.84 and 0.72 events per 100 patient-years respectively. The rate was below the reported age-matched population rate of 1.0 per 100 patient-years.

Retinal events were also rare and remained below the age-matched population rate.

The findings are relevant because safety concerns around stimulating blood vessel growth have been one of the barriers to development of therapeutic angiogenesis.

Why angiogenesis matters in coronary disease

When coronary arteries become narrowed or blocked, the heart can respond by forming new blood vessels in an attempt to restore blood supply to oxygen-deprived tissue.

This natural process, known as angiogenesis, is often insufficient in people with coronary artery disease. Therapeutic approaches have therefore sought to increase blood vessel formation in ischaemic tissue.

However, clinical development of these approaches has produced limited results. Earlier strategies have largely focused on increasing levels of vascular endothelial growth factor A (VEGF-A), a key regulator of blood vessel formation.

Isomab is developing ISM-001 as a different approach to therapeutic angiogenesis. Rather than directly stimulating blood vessel growth, the antibody is designed to target VEGF-A165b, an isoform that inhibits angiogenesis.

Professor David Bates, Isomab’s chief scientific officer and a study author, said: “These findings represent an important step forward for the field of therapeutic angiogenesis. They resolve safety questions that have clouded the perception of an entire class of treatments and give us a strong foundation as we advance ISM-001 towards first-in-human studies.”

Isomab prepares for clinical development

Isomab plans to advance ISM-001 towards first-in-human testing in patients with chronic angina who remain symptomatic despite available treatment.

The company’s approach is based on research into VEGF-A165b, which Bates discovered in 2001. Subsequent research has investigated its role as an inhibitor of blood vessel growth.

The company believes that blocking VEGF-A165b could remove an inhibitory mechanism affecting angiogenesis and allow the body’s existing blood-vessel-forming processes to improve blood flow in ischaemic tissue.

The new clinical safety analysis does not establish whether ISM-001 will be effective in patients. Rather, it addresses a safety question surrounding the wider therapeutic angiogenesis field and provides additional context for the development of new approaches.

Philip Brainin, Isomab’s CEO, said the company believes there is an opportunity to develop disease-modifying treatment for patients with coronary artery disease.

“Given the scale and continuing burden of coronary artery disease, the opportunity to change the course of the disease is enormous. With ISM-001 we are looking to introduce a new treatment paradigm – rebalancing VEGF-A signaling to unlock the heart’s own capacity to heal itself,” Brainin said.

The ESC 2026 presentation therefore provides clinical safety evidence relevant to a field that has struggled to translate the biological potential of therapeutic angiogenesis into effective treatments. Isomab now intends to take its alternative approach into human clinical development.