Slide 1: Inhaled Molgramostim Improves Pulmonary Gas Exchange and Respiratory Quality of Life in aPAP: Results from IMPALA-2
Inhaled Molgramostim Improves Pulmonary Gas Exchange and Respiratory Health-Related Quality of Life in Patients with Autoimmune Pulmonary Alveolar Proteinosis: Results from IMPALA-2 Cormac McCarthy, MD, PhD, FRCPI UCD School of Medicine St Vincent’s University Hospital, Dublin 4, Ireland
Slide 2: Disclosures
Disclosures • Savara Inc., Scientific Advisory Board and Consultancy • Partners Therapeutics Inc., Consultancy • Health Research Board Ireland, Grant Funding • Enterprise Ireland, Grant Funding • EU Horizon MCSA, Grant Funding • The LAM Foundation, Scientific Advisory Board Member • The LAM Foundati
Slide 3: Pulmonary Alveolar Proteinosis (PAP)
Pulmonary Alveolar Proteinosis (PAP) • Rare syndrome, not a specific disease • Characterised by progressive accumulation of alveolar surfactant • Foamy lipid-laden alveolar macrophages • Restrictive lung impairment, hypoxic respiratory insufficiency, and, in severe cases, respiratory failure and dea
Slide 4: Autoimmune PAP (aPAP)
Autoimmune PAP (aPAP) • aPAP is caused by autoantibodies to GM-CSF1,2 • The prevalence of aPAP is 6 to 27 per 1 million in the general population3-5 • Accounts for 90% of all PAP cases3 • Molgramostim inhalation solution is a form of recombinant GM-CSF – Administered using a proprietary investigatio
Slide 5: Phase 3 IMPALA-2 Trial Design
Phase 3 IMPALA-2 Trial Design Period 1: Double-blind Period 2: Open-label (ongoing, not part of results) 6-Week Screening n=81 • DLCO% ≤70% predicted molgramostim 300 μg daily dosing at first screening and baseline molgramostim 300 μg daily dosing • Change in % predicted n=83 DLCO% <15% points to W1
Slide 6: IMPALA-2: Baseline Clinical Characteristics
IMPALA-2: Baseline Clinical Characteristics Molgramostim Placebo N=81 N=83 DLCO% Mean (SD) 52.6 (11.7) 52.6 (10.4) Median 54 55 Range 25-72 28-71 SGRQ Total Score* Mean (SD) 39.5 (19.2) 41.2 (18.1) Median 42.2 44.0 Range 0-87 2-84 Exercise Capacity Mean (SD) 7.1 (2.2) 7.2 (2.1) Peak METs† Median 7.3
Slide 7: Improves Pulmonary Gas Transfer: DLCO%
IMPALA-2 Results: Molgramostim Improves Pulmonary Gas Transfer DLCO% 15 Molgramostim (N=81) Molgramostim (n=81) Placebo (N=83) Change from Baseline LSM Change Between- 10 from group LSM LSM ± SE P-value Baseline difference* Week 24 Mol: 9.8 6.00 0.0007 5 Pbo: 3.8 Week 48 Mol: 11.6 6.90 0.0008 Placeb
Slide 8: Improves Respiratory Health-Related Quality of Life: SGRQ Total Score
IMPALA-2 Results: Molgramostim Improves Respiratory Health-Related Quality of Life SGRQ Total Score 5 Molgramostim (N=81) Placebo (N=83) Change from Baseline 0 LSM Change Between- Placebo (n=83) from group LSM P-value LSM ± SE -5 Baseline difference* Week 24 Mol: -11.5 -6.59 0.0072† -10 Pbo: -4.9 -1
Slide 9: Improves Respiratory Health-Related Quality of Life: SGRQ Activity Score
IMPALA-2 Results: Molgramostim Improves Respiratory Health-Related Quality of Life SGRQ Activity Score 5 Change from Baseline 0 LSM Change Between- Placebo (n=83) from group LSM P-value Baseline difference* LSM ± SE -5 Week 24 Mol: -13.0 -7.81 0.0149† -10 Pbo: -5.2 -15 Week 48 Mol: -13.4 -5.99 0.121
Slide 10: Improves Patient Function: Peak Exercise Capacity (METs)
IMPALA-2 Results: Molgramostim Improves Patient Function Peak Exercise Capacity (METs) 1.5 Molgramostim (n=81) LSM Change Between- Change from Baseline from group LSM P-value 1.0 Baseline difference* LSM ± SE Week 24 Mol: 1.11 0.41 0.0845 Pbo: 0.70 0.5 Placebo (n=83) Week 48 Mol: 1.13 0.55 0.0234† P
Slide 11: Reduces Pulmonary Surfactant Burden: Ground Glass Opacity Score
IMPALA-2 Results: Molgramostim Reduces Pulmonary Surfactant Burden Ground Glass Opacity Score (Week 24) 1 p=0.0004* Change From Baseline 0 Mean ± SE -1 -2 -3 Molgramostim Placebo (N=78) (N=79) *P-value based on post-hoc analysis. GGO, ground glass opacity. 11
Slide 12: Reduces Pulmonary Surfactant Burden: Rescue WLL Use
IMPALA-2 Results: Molgramostim Reduces Pulmonary Surfactant Burden Rescue WLL Use (entire 48-week period) 12 Number of Procedures 10 8 6 4 2 (7.4%) (13.3%) 0 Molgramostim Placebo (N=81) (N=83) Whole lung lavage was permitted as a rescue therapy during the 48-week, double-blind treatment period. 12 W
Slide 13: IMPALA-2 Results: Molgramostim Is Well Tolerated
IMPALA-2 Results: Molgramostim Is Well Tolerated Adverse events (AEs) AEs in >10% of patients in any treatment arm during AEs during the double-blind treatment period the double-blind treatment period Molgramostim Placebo Molgramostim Placebo Treatment-Emergent N=81 N=83 Treatment-Emergent N=81 N=83
Slide 14: IMPALA-2: Conclusions
IMPALA-2: Conclusions • Largest and longest controlled trial of inhaled GM-CSF therapy for aPAP ever conducted • Improvement in DLCO% demonstrated • Achieved improvement in multiple secondary and exploratory endpoints – Pulmonary surfactant burden – Pulmonary gas exchange – Quality of life – Exercis
Slide 15: Questions
ST. VINCENT'S UNIVERSITY HOSPITAL Elm Park Questions 15