Molbreevi (molgramostim) / Savara, Nobelpharma - LARVOL DELTA

The Effects of Molgramostim on Respiratory Health-related Quality of Life and Patient-reported Outcomes in Patients With Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (ATS 2025) - "Molgramostim improved HRQoL as measured by SGRQ Impact and Symptom scores. More aPAP patients on molgramostim than on placebo reported improvements in mobility, self-care, usual activities, and pain/discomfort (EQ-5D-5L), as well as improvements in breathing problems and physical activity level (PGIS and PGIC)."

Clinical • HEOR • Patient reported outcomes • CNS Disorders • Depression • Immunology • Mood Disorders • Pain • Psychiatry • Respiratory Diseases • CSF2

Molgramostim Reduces Surfactant Burden and Number of Whole Lung Lavage Procedures in Patients With Autoimmune Pulmonary Alveolar Proteinosis (aPAP): Results From the IMPALA-2 Phase 3 Clinical Trial (ATS 2025) - "Molgramostim was associated with reduced surfactant burden as measured by reduced GGO score and a smaller proportion of patients undergoing WLL procedures over the 48-week blinded intervention period compared with placebo. The observation that molgramostim reduced pulmonary surfactant burden, which drives the clinical manifestations of aPAP lung disease, provides strong support for a beneficial treatment effect of molgramostim in patients with aPAP."

Clinical • P3 data • Surfactant • Immunology • Pulmonary Disease • Respiratory Diseases • CSF2

Savara Announces Encore Presentations From the Phase 3 IMPALA-2 Trial of Molgramostim Inhalation Solution (Molgramostim) in Patients With Autoimmune Pulmonary Alveolar Proteinosis (aPAP) at Two Upcoming Scientific Conferences (Businesswire) - "Savara Inc...announced encore presentations of top-line data from the pivotal, Phase 3 IMPALA-2 clinical trial of molgramostim in aPAP will be presented at the 65th Congress of the German Society of Pneumology (DGP) in Leipzig, Germany taking place April 9-12 and at the 65th Annual Meeting of the Japanese Respiratory Society (JRS) taking place April 11-13, 2025, in Tokyo, Japan."

P3 data: top line • Respiratory Diseases

Savara Reports Fourth Quarter and Year End 2024 Financial Results and Provides Business Update (Businesswire) - "'MOLBREEVI has the potential to be the first and only approved therapy for aPAP in the U.S. and Europe and could redefine the standard of care for the disease. If granted Priority Review, we could have a PDUFA date by the end of the year and are preparing for a commercial launch in early 2026. Lastly, with approximately $196 million in cash, we are in a strong financial position and believe our cash runway extends through 2Q 2027, excluding our recent debt financing which adds additional low-cost capital options to further finance the Company.'"

Commercial • FDA approval • Launch • Respiratory Diseases

Savara Enters Into Non-Dilutive Debt Financing for up to $200M With Hercules Capital (Businesswire) - "Savara...announced that it has entered into a loan and security agreement with Hercules Capital...for up to $200 million. Access to the additional capital strengthens Savara’s balance sheet following the submission of the Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for MOLBREEVI as a treatment for autoimmune pulmonary alveolar proteinosis (aPAP)....Under the terms of this loan agreement, $30 million was funded on the execution of the agreement and will be used to repay the Company’s existing $26.5 million debt facility. An additional $100 million will become available upon FDA approval of MOLBREEVI and certain other milestones. The final $70 million may be made available upon request by the Company and at the discretion of Hercules Capital."

Financing • Respiratory Diseases

Savara Completes Submission of the Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for MOLBREEVI as a Treatment for Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (Businesswire) - "...'As part of the submission, Priority Review was requested and, if granted, would shorten the FDA’s review to six months (from the standard ten months) following the Agency’s acceptance of the application....Our commercial preparations are on-track to support a potential launch in early 2026'. The IMPALA-2 trial met its primary endpoint, with MOLBREEVI achieving statistically significant improvement from baseline in percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO), a well-established measure of pulmonary gas exchange, compared to placebo at Week 24....Company Remains on Track to Submit the Marketing Authorization Application (MAA) in Europe by the End of 2025."

EMA filing • FDA filing • Launch US • Respiratory Diseases

Savara to Present New Data From the Phase 3 IMPALA-2 Trial of Molgramostim Inhalation Solution (Molgramostim) in Patients With Autoimmune Pulmonary Alveolar Proteinosis (aPAP) at the American Thoracic Society International Conference 2025 (Businesswire) - "Savara Inc...announced the acceptance of two abstracts for poster presentation at the American Thoracic Society (ATS) International Conference taking place May 16-21, 2025, in San Francisco, CA. The Company will also host an Industry Theater titled 'Advances in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)' at the meeting."

Clinical data • P3 data • Respiratory Diseases

Long-term outcomes in five patients with autoimmune pulmonary alveolar proteinosis treated with molgramostim inhalation solution. (PubMed, ERJ Open Res) - "Studies have explored inhaled GM-CSF augmentation as a primary treatment for aPAP [5-12]. In this real-world case series, we present the beneficial long-term effects of molgramostim inhalation solution, an investigational, recombinant GM-CSF, in five aPAP patients with therapeutic disease challenges."

Journal • Immunology • Pulmonary Disease • Respiratory Diseases • CSF2

Molgramostim improves pulmonary gas exchange in patients with autoimmune pulmonary alveolar proteinosis (aPAP): results from the IMPALA-2 phase 3 clinical trial (BTS WM 2024) - "All patients who completed double-blind treatment continued in the open-label period. Conclusions Molgramostim was well tolerated and improved pulmonary gas exchange, respiratory health-related quality of life, and EC of patients with aPAP."

Clinical • P3 data • Immunology • Pulmonary Disease • Respiratory Diseases • CSF2

Pulmonary Alveolar Proteinosis; Treatment Update by Clinical Trials (KATRDIC 2024) - "One Japanese study has shown that GM-CSF (sargramostim) inhalation can improve significantly compared with placebo inhalation (Tazawa, et al...The other global clinical trial of GM-CSF (molgramostim) inhalation could not show the significant effects (Trapnell, et al...This year is epoch making for APAP patients. I would like to show you the history of GM-CSF inhalation therapy during the past 20 years."

Clinical • Anesthesia • Immunology • Respiratory Diseases • CSF2

IMPALA-2: Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (clinicaltrials.gov) - P3 | N=160 | Active, not recruiting | Sponsor: Savara Inc. | Trial completion date: Jun 2025 ➔ Nov 2024 | Trial primary completion date: Jun 2024 ➔ Nov 2023

Trial completion date • Trial primary completion date • Immunology • Respiratory Diseases

RCT Abstract - Inhaled molgramostim improves pulmonary gas exchange and respiratory health-related quality of life (HRQoL) in patients with autoimmune pulmonary alveolar proteinosis (aPAP): Results from IMPALA-2 (ERS 2024) - "Molgramostim was well tolerated and significantly improved pulmonary gas exchange and respiratory HRQoL in aPAP patients."

Clinical • HEOR • Immunology • Pulmonary Disease • Respiratory Diseases • CSF2

Inhaled molgramostim therapy for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP): a plain language summary of the IMPALA trial. (PubMed, Hosp Pract (1995)) - No abstract available

Journal • Immunology • Respiratory Diseases

Molgramostim Nebulizer Solution Expanded Access Program Protocol (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Savara Inc.

New trial • Immunology • Respiratory Diseases

IMPALA-EX: Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis (clinicaltrials.gov) - P3 | N=60 | Terminated | Sponsor: Savara Inc. | Completed ➔ Terminated; SAV006-03 was initiated before the evaluation of the IMPALA study (NCT02702180) results. Considering these results and authority advice there would not be adequate efficacy and safety data from SAV006-03 and the study was terminated.

Trial termination • Immunology • Respiratory Diseases

Inhaled Molgramostim in Pediatric Participants With Autoimmune Pulmonary Alveolar Proteinosis (aPAP). (clinicaltrials.gov) - P3 | N=5 | Not yet recruiting | Sponsor: Savara Inc.

New P3 trial • Immunology • Pediatrics • Respiratory Diseases • CSF2

OPTIMA: An Open-Label, Non-comparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection. (PubMed, Ann Am Thorac Soc) - P2 | "In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. There was less benefit seen in MABS. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted."

Journal • Nontuberculous mycobacteria • Bronchiectasis • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • CSF2

GI-HOPE: Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Inhalation to Improve Host Defense and Pulmonary Barrier Restoration (clinicaltrials.gov) - P2 | N=45 | Completed | Sponsor: University of Giessen | Active, not recruiting ➔ Completed

Trial completion • CD80 • CD86 • CRP • CSF2 • MRC1

IMPALA-2: Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (clinicaltrials.gov) - P3 | N=160 | Active, not recruiting | Sponsor: Savara Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Respiratory Diseases • CSF2

GI-COVID: GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia (clinicaltrials.gov) - P2 | N=63 | Completed | Sponsor: University of Giessen | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Sep 2022 | Trial primary completion date: Dec 2022 ➔ Jun 2022

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CRP • CSF2 • IL6

Effect of rhGM-CSF on the Healing of Venous Leg Ulcers (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Reponex Pharmaceuticals A/S | Recruiting ➔ Active, not recruiting | N=48 ➔ 6 | Trial completion date: May 2022 ➔ Dec 2023 | Trial primary completion date: May 2022 ➔ Dec 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Venous Ulcer

IMPALA-2: choice of DLCO as a primary endpoint in aPAP (ERS 2022) - P2, P3 | "Diffusing capacity of the lung for carbon monoxide (DLCO) is a standardized measure of pulmonary gas transfer used in clinical practice.2 The phase 2 IMPALA (NCT02702180) study demonstrated improvements in DLco among aPAP patients who responded to inhaled molgramostim nebulizer solution (MOL); the estimated difference (95% CI) between MOL vs placebo (PBO) was 7.8 (2.3–13.3).1 Objective: To describe the rationale for using DLCO as the primary endpoint in IMPALA-2 (NCT04544293), a pivotal, randomized, global study of MOL administered in aPAP... DLCO is a convenient, standardized, and widely-used lung function test that is directly relevant to the pathophysiology of aPAP and is considered suitable for use as the primary endpoint in IMPALA-2 for daily MOL among patients with aPAP."

Immunology • Rare Diseases • Respiratory Diseases

Safety and tolerability of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis (aPAP) (ERS 2022) - P2, P3 | "IMPALA-X was discontinued early as intermittent dosing did not show a benefit vs placebo in the IMPALA study. The phase 3 IMPALA-2 study of continuous daily MOL vs placebo in patients with aPAP is ongoing."

Clinical • Cough • Immunology • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

IMPALA: efficacy measures in patients who required whole lung lavage (ERS 2022) - P2 | "Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease and whole lung lavage (WLL) is the current standard of care.1 Objective: Post hoc analysis of IMPALA (NCT02702180) evaluated the benefit of continuous (daily) inhaled molgramostim nebulizer solution (MOL; 300 μg) vs placebo (PBO) among aPAP patients who required WLL during the treatment period.1 Change from baseline (BL) in the following efficacy measures were analyzed in patients who received WLL: alveolar-arterial oxygen difference (AaDO2), diffusing capacity of the lungs for carbon monoxide (%DLCO), and Saint George’s Respiratory Questionnaire total (SQRG-T) and activity (SQRG-A) scores... After WLL, aPAP patients treated with MOL had greater improvements in measures of gas exchange and health status vs PBO."

Clinical • Immunology • Pulmonary Disease • Respiratory Diseases

"$SVRA Savara Awarded Promising Innovative Medicine (PIM) Designation in the United Kingdom (UK) for Molgramostim Nebulizer Solution (Molgramostim) in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) https://t.co/JiRKGjXlIw" (@stock_titan)

Immunology • Respiratory Diseases