Slide 1: In Vivo Efficacy of Inhaled PDGFRα/β Inhibitor GB002 in PAH Model
Scientific Sessions 2019 In Vivo Efficacy of a Novel, Inhaled PDGFRα/β Inhibitor, GB002, in the Rat Monocrotaline and Pneumonectomy Model of Pulmonary Arterial Hypertension Ravikumar Sitapara, Debbie Slee, Luisa Salter-Cid, Lawrence Zisman
Slide 2: Disclosures
Disclosures • The presenter, Lawrence Zisman is employed by Gossamer Bio, San Diego CA and owns stock in Gossamer Bio Inc. ScientificSessions.org #AHA19
Slide 3: Background and Hypothesis
Background and Hypothesis • The PDGF pathway drives adverse vascular remodeling in pulmonary arterial hypertension (PAH). • GB002 is a novel, potent, clinical stage inhibitor of PDGFRα/β kinases. • GB002 is formulated as a dry powder and delivered by inhalation. • The rat Monocrotaline (MCT) Pneumon
Slide 4: Study Design
Study Design BID GB002 and vehicle administered BID for 11 days ScientificSessions.org #AHA19
Slide 5: GB002 prevented progression of severe pulmonary hypertension in the MCT-PN model
GB002 prevented progression of severe pulmonary hypertension in the MCT-PN model 100 Vehicle * Vehicle (n=12) 80 GB002 * * GB002 (n=7) PASP (mmHg) 60 *p<0.05 40 34% 37% 41% 20 0 0 1 2 3 4 5 6 7 8 9 10 11 Day On day 9, 10, and 11, PASP was 34%, 37%, and 41% lower, respectively, in the GB002 gro
Slide 6: GB002 significantly decreased RVESP and RV hypertrophy
GB002 significantly decreased RVESP and RV hypertrophy Vehicle (n=6) GB002 (n=11) 100 0.8 *p<0.001 RVESP (mmHg) 80 0.6 Fulton's Index (RV/(LV+IVS)) 60 40 * 0.4 * 20 0.2 0 0.0 Vehicle GB002 Vehicle GB002 Data presented as mean ± SEM. ScientificSessions.org #AHA19
Slide 7: GB002 decreased neointimal lesions and fibrosis
GB002 decreased neointimal lesions and fibrosis VEHICLE GB002 ScientificSessions.org #AHA19
Slide 8: GB002 reverse remodeled pulmonary arterioles
GB002 reverse remodeled pulmonary arterioles Vehicle GB002 Vehicle Grade 2 GB002 Grade 0 1.5 100 * Grade 2 * Grade 1 Lumen/ Media 80 * % of lesions 1.0 Grade 0 60 0.5 40 Vehicle (n=6) GB002 (n=11) 20 0.0 0 *p<0.0001 Vehicle GB002 Vehicle GB002 Data presented as mean ± SEM; Grading system per Toba et
Slide 9: Summary and Conclusions
Summary and Conclusions • GB002 is a novel inhaled PDGFRα/β inhibitor with potentially disease-modifying characteristics • In the rat MCT PN model, a severe model of PAH that closely replicates key features of the human disease, inhaled GB002 prevented: ▪ Progression of pulmonary arterial hypertensi
Slide 10: Acknowledgments
Acknowledgments • The work performed in this study was supported by NIH grant HL102946 • Team at Gossamer Bio: Ravi Sitapara, Anna Galkin, Laura Carter, Debbie Slee, Luisa Salter-Cid ScientificSessions.org #AHA19
Slide 11: Thank you!
Thank you! ScientificSessions.org #AHA19