Slide 1: GB002, A Novel, Inhaled PDGFR Kinase Inhibitor, Demonstrates Efficacy in the SU5416 Hypoxia Rat Model of PAH
Moderated Digital Poster 428 GB002, A Novel, Inhaled PDGFR Kinase Inhibitor, Demonstrates Efficacy in the SU5416 Hypoxia Rat Model of Pulmonary Arterial Hypertension Anna Galkin, Bryan Clemons, Eduardo Garcia, Jennifer Brooks, Debbie Slee, Luisa Salter-Cid, Larry Zisman Gossamer Bio, Inc.; San Diego
Slide 2: Disclosures
Disclosures • Gossamer Bio Inc. Employee • Gossamer Bio Stock Options ScientificSessions.org #AHA19
Slide 3: Introduction: PDGF Signaling Contributes to Pulmonary Arterial Remodeling in PAH
Introduction: Platelet-Derived Growth Factor (PDGF) Signaling Contributes to Pulmonary Arterial Remodeling in PAH • PDGFR signaling drives vascular remodeling in preclinical models of PAH Healthy PAH • Evidence for cross-talk between PDGFR and BMPR2, a key causal gene in hereditary PAH PDGFRα • PDGF
Slide 4: Introduction: GB002, a Novel Inhaled PDGFRα/β Inhibitor, in Clinical Development for PAH
Introduction: GB002, a Novel Inhaled PDGFRα/β Inhibitor, in Clinical Development for PAH • Imatinib, a non-selective PDGFR inhibitor, GB002 Imatinib improved exercise capacity and hemodynamics PDGFRα IC50 (nM) 2 7 12 in patients with advanced PAH in the Phase III IMPRES trial, however, serious adver
Slide 5: Materials and Methods: Evaluation of GB002 vs Imatinib in the SU5416/Hypoxia Rat PAH Model
Materials and Methods: Evaluation of GB002 vs Imatinib in the SU5416 / Hypoxia Induced Rat PAH Model * GB002 delivered dose estimated using Guyton’s formula (Guyton 1947) ** Imatinib in vivo exposures matched to published 400 mg dose clinical exposures (Gschwind et al. Drug Metabolism and Dispositio
Slide 6: Results: GB002 Treatment Restored Rat Lung BMPR2 Expression and Improved Hemodynamic Parameters
Results: GB002 Treatment Restored Rat Lung BMPR2 Expression and Led to Significant Improvement in Hemodynamic Parameters n.s. Fold Change vs Healthy Control p<0.05 n.s. p<0.05 p<0.005 80 150 1.5 Right Ventricular Systolic p<0.005 p<0.005 Mean Pulmonary Arterial Lung BMPR2/Actin Pressure (mm Hg) Pres
Slide 7: Results: 2-Week Treatment with GB002 Reduced Pulmonary Blood Vessel Remodeling
Results: 2-Week Treatment with GB002 Reduced Pulmonary Blood Vessel Remodeling in the Rat SU5416/Hypoxia PAH Model 120 * p<0.05 ** p<0.01 100 • Development of PAH in the current 80 model led to a 15-fold increase in % Non-Muscular of muscular vessels % 60 Partially-Muscular 40 Muscular • GB002 treat
Slide 8: Results: GB002 Treatment Reduced Circulating Plasma NT-proBNP
Results: GB002 Treatment Reduced Circulating Plasma NT-proBNP in SU5416/Hypoxia Rat PAH Model n.s. Mean NT-proBNP (pg/ml) SEM 3000 p<0.05 • NT-proBNP plasma levels correlate with functional 2000 parameters and patient outcome in PAH1 • Rat NT-proBNP plasma levels increased 9-fold in the 1000 Vehic
Slide 9: Results: GB002 Modulated Circulating Plasma Levels of TNFα, IL10 and PDGF-BB
Results: GB002 Treatment Modulated Circulating Plasma Levels of TNFα, IL10 and PDGF-BB in SU5416/Hypoxia Rat PAH Model 8 p<0.0002 100 p<0.05 800 • GB002 treatment led to a 600 significant 2-fold reduction in PDGF-BB (pg/ml) 80 6 TNF (pg/ml) 400 IL10 (pg/ml) 60 200 circulating plasma levels of TNFα
Slide 10: Conclusions
Conclusions • GB002 is a novel inhaled PDGFRα/β inhibitor in clinical development for PAH (Phase Ib, NCT03926793) • Localized lung delivery of GB002 was efficacious on multiple measures of disease activity in the SU5416/Hypoxia Rat PAH model, in that it • Displayed improvement in cardiopulmonary hem
Slide 11: Acknowledgments
Acknowledgments • IPS Therapeutique, Sherbrooke, Canada ScientificSessions.org #AHA19
Slide 12: Thank you!
Thank you! ScientificSessions.org #AHA19