LB-2 | VEGF Gene Therapy Improves Exercise Time, Ischemia, and Symptoms in Patients with Refractory Angina: Results of the Phase II EXACT Trial

XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of vascular endothelial growth factor to more safely and potently induce angiogenesis. The EXACT trial (NCT04125732) assessed the safety and preliminary efficacy of XC001 in patients with "no option" refractory angina (NORA). Single-arm, multicenter, open-label trial of 32 patients with NORA received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. There were no SAEs attributed to study drug. Twenty expected SAEs in 13 patients were related to the surgical procedure. Total exercise duration (TED) increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months) (+88.3 [95% CI 37.1–139.5] and +84.5 [34.1–134.9], and +115.5 seconds [59.1-171.9] at 3, 6, and 12 months) (Fig. 1). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI -3.1–23.5%), 14.3% (2.8–25.7%), and 10.2% (-0.8-21.2%). Time to onset of ST depression during exercise tolerance testing increased by 105.2 (95% CI -27.9–238.3), 113.6 (28.8–198.4), and 103.1 seconds (26.7–179.5). Angina frequency decreased by -7.7 (95% CI 4.1–11.3), -6.6 (3.5–9.7), and -8.8 episodes (4.6–13.0). Angina class improved in 81% of participants at 6 months. XC001 administered via transepicardial delivery is safe and generally well-tolerated in NORA. Exploratory improvements in exercise duration, ischemic burden, and angina frequency and severity support a biologic effect sustained to 12 months, warranting further investigation.