Introduction Seralutinib, a novel, inhaled kinase inhibitor with anti-inflammatory and anti-proliferative effects, met the primary endpoint of reduction in pulmonary vascular resistance in the phase 2 TORREY trial in PAH (NCT04456998) and has the potential to treat pulmonary vascular remodeling. This abnormal remodeling includes distal pruning and proximal pulmonary arterial dilation. Quantitative analysis of these features is possible with CT imaging.

Methods The TORREY CT substudy used thin-section, volumetric non-contrast chest CTs followed by automated pulmonary vascular segmentation to evaluate the reverse remodeling potential of seralutinib. Baseline and Week 24 blood vessel volumes (BVVs) were determined at distinct levels defined by vessel cross-sectional area (CSA) in 19 subjects on a background of 2-3 approved PAH therapies. BVVs of pulmonary arteries with a CSA <5mm2 (BV5A) and >10mm2 (BV10A) were calculated. The BV5A to BV10A ratio (BV510ARATIO) was used to express relative redistribution of pulmonary arterial BVV. Linear regression was used to model the treatment effect.

Results The BV510ARATIO increased from baseline to Week 24 in the seralutinib group (n=7) vs. placebo (n=12; p=0.028), and BV510ARATIO changes correlated with changes in stroke volume (R=0.65, p=0.0033) and pulmonary artery compliance (R=0.56, p=0.016).

Conclusion In heavily treated PAH subjects, adding seralutinib for 24 weeks led to a significant redistribution of pulmonary arterial BVV to smaller vessels. These data visualize and quantify seralutinib?s treatment effect on the pulmonary arterial vasculature in PAH.