Inhaled seralutinib improved cardiopulmonary hemodynamics and inflammatory biomarkers, reduced N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, and reversed remodeling of the pulmonary vasculature in 2 animal models of pulmonary arterial hypertension (PAH). The treatment was found to be more effective than imatinib. These results were published in the European Respiratory Journal.

“We are excited to share some of the preclinical foundations for the seralutinib program in such a high impact scientific journal,” Faheem Hasnain, the cofounder, chairman, and chief executive officer of Gossamer Bio, said in a press release

PAH is characterized by the interplay of platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R), and c-KIT signaling. Seralutinib is a small-molecule PDGFR/CSF1R/c-KIT kinase inhibitor. It is currently being tested in a phase 2 clinical trial in patients with PAH.


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For the study, the team led by Lawrence S. Zisman, MD, senior director at Gossamer Bio, evaluated the pharmacokinetics and pharmacodynamics of inhaled seralutinib in healthy rats. They also compared the potency and selectivity of seralutinib with those of imatinib. Finally, they evaluated the efficacy of inhaled seralutinib in 2 rat models of PAH. 

The results showed that seralutinib strongly inhibited PDGFRα/β, c-KIT, and CSF1R and increased bone morphogenetic protein receptor type 2 (BMPR2). 

It also improved cardiopulmonary hemodynamics and reduced the muscularization of the small pulmonary artery and right ventricular hypertrophy in both models. In 1 model, it improved cardiopulmonary hemodynamics, restored lung BMPR2 levels, and decreased NT-proBNP levels more than imatinib. 

The researchers also conducted some experiments in PAH lung samples from rats and humans and showed that seralutinib led to increases in PDGFR, CSF1R, and c-KIT. Finally, they identified candidates that could mediate the effects of seralutinib on BMPR2 through microRNA analysis.

References

Galkin A, Sitapara R, Clemons B, et al. Inhaled seralutinib exhibits potent efficacy in models of pulmonary arterial hypertension. Eur Respir J. Published online June 9, 2022. doi:10.1183/13993003.02356-2021

Gossamer Bio announces publication of key preclinical data in the European Respiratory Journal highlighting seralutinib’s potential for the treatment of PAH. News release. Gossamer Bio, Inc; June 9, 2022.

GB002 in adult subjects with pulmonary arterial hypertension (PAH). ClinicalTrials.gov. July 7, 2020. Updated May 25, 2022. Accessed June 16, 2022.