Savara Inc

Business Overview

Savara Inc. (together with its subsidiaries “Savara,” the “Company,” “we,” “our” or “us”) is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our sole program, molgramostim inhalation solution ("MOLBREEVI"or "molgramostim"), is an investigational inhaled biologic, specifically an inhaled granulocyte-macrophage colony-stimulating factor ("GM-CSF") in Phase 3 development for autoimmune pulmonary alveolar proteinosis (“autoimmune PAP”). MOLBREEVI is delivered via a proprietary eFlow®Nebulizer System (PARI Pharma GmbH, “PARI”).

Corporate Strategy

Our goal is to become a leader in rare respiratory therapeutics through the development and commercialization of novel, best-in-class medicines that address unmet medical needs in this field. Key elements of our strategy include:

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Continued advancement of the MOLBREEVI autoimmune PAP program, the completion of the Phase 3 IMPALA-2 pivotal clinical trial of which the 96-Week open-label period of the trial is ongoing and pursuing regulatory approval. The IMPALA-2 trial design was endorsed by regulatory authorities in the U.S. (U.S. Food and Drug Administration), Europe (European Medicines Agency), United Kingdom (Medicines and Healthcare Products Regulatory Agency), and Japan (Pharmaceuticals and Medical Devices Agency), and regulatory agencies and ethics committees in various countries and sites where the trial is being conducted. Having enrolled 164 patients (target enrollment was 160 patients), IMPALA-2 is the largest placebo-controlled trial in autoimmune PAP, and in June 2024 positive top line results from the trial were reported that demonstrated a favorable risk benefit profile for MOLBREEVI in autoimmune PAP. In March 2025, the biologics license application (“BLA”) for MOLBREEVI in autoimmune PAP was submitted to the U.S. Food and Drug Administration (“FDA”). In May 2025, we announced the receipt of a Refusal to File letter ("RTF") from the FDA. The RTF was not the result of safety concerns, the FDA did not request or recommend additional efficacy studies, and it did not impact previous designations granted by regulators for MOLBREEVI in autoimmune PAP. We resubmitted the BLA in December 2025 and requested Priority Review. In February 2026, the FDA formally filed the BLA for MOLBREEVI and granted Priority Review. MOLBREEVI in autoimmune PAP has been granted Fast Track and Breakthrough Therapy Designations by the FDA, Orphan Drug Designation by the FDA and the European Medicines Agency (EMA), as well as Innovation Passport (IP) and Promising Innovative Medicine (PIM) designations by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA).

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Ensuring all aspects of our manufacturing are validated and can produce product at commercial scale. With the goal of establishing an uninterrupted supply chain and to mitigate approvability risk, we have selected high-quality CMO’s with proven track-records to support our chemistry, manufacturing, and controls ("CMC") activities. In February 2024, we entered into a Master Services Agreement with FUJIFILM Diosynth Biotechnologies (“Fujifilm”) to complete a technology transfer of the drug substance manufacturing process from GEMA Biotech S.A. (“GEMA”) and to manufacture commercial supply of MOLBREEVI. GEMA is the original drug substance manufacturer that supplied the IMPALA and IMPALA-2 clinical trials. Following the RTF from the FDA, we held a Type A meeting with the FDA. At that meeting, we gained alignment with FDA on the requirements necessary to show comparability between drug substance manufactured at GEMA and drug substance manufactured at Fujifilm and, subsequently, decided to resubmit the BLA with Fujifilm as the drug substance supplier. As part of the technology transfer process, we validated the Fujifilm drug substance manufacturing with three process performance qualification (“PPQ”) batches, and we believe the technology transfer meets the requirements outlined by the FDA. Fujifilm is manufacturing MOLBREEVI drug substance at commercial scale. We continue to work with GEMA and may decide to use them as a second source of drug substance supply following approval with Fujifilm as the drug substance manufacturer. Drug product is currently manufactured at Patheon UK Ltd. (“Patheon”), a division of ThermoFisher Scientific Inc. Following commercialization of MOLBREEVI, and pursuant to our strategy for a dual source supply chain, we plan to qualify a second source drug product manufacturer. For the supply of our exclusive, proprietary eFlow® nebulizer system that is part of the MOLBREEVI drug-device combination, we have a long-term supply agreement in place with PARI. PARI has five FDA-approved nebulizers based on the same eFlow® technology that is used in the proprietary device with MOLBREEVI. The PARI eFlow® nebulizer was used in the IMPALA and IMPALA-2 trials, and we have completed a series of lab tests and human factors studies in an effort to satisfy regulatory requirements for a drug-device combination.

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Outsourcing capital-intensive operations. We will continue to pursue the development and manufacturing of our product candidate by outsourcing most clinical development work and manufacturing operations. We believe our business model enables the effective and capital-efficient development of our pipeline through the use of high-quality specialist vendors and consultants.

MOLBREEVI – Autoimmune PAP

Our sole product candidate, MOLBREEVI, is an inhaled biologic. MOLBREEVI is an inhaled formulation of recombinant human GM-CSF and is being developed for the treatment of autoimmune PAP. Pulmonary alveolar proteinosis (“PAP”) is a rare lung disease characterized by the accumulation of surfactant in the alveoli (or air sacs) of the lungs. There are different types of PAP, of which autoimmune PAP is the most common.

In May 2019, the FDA granted Fast Track Designation to MOLBREEVI for the treatment of autoimmune PAP. Fast Track Designation facilitates the development and expedites the review of new drugs or biologics intended to treat serious or life-threatening conditions that demonstrate the potential to address unmet medical needs. In December 2019, the FDA granted Breakthrough Therapy Designation (“BTD”) for MOLBREEVI in autoimmune PAP based on data from the 24-Week double-blind treatment period from our IMPALA Phase 2/3 trial. Additionally, MOLBREEVI was granted Orphan Drug Designation for the treatment of autoimmune PAP in the U.S. and the European Union (“EU”), which allows for seven and ten years of exclusivity from approval, respectively. Savara has exclusive access to the investigational, proprietary PARI eFlow® Nebulizer System for this indication along with a proprietary cell bank for the active drug substance of MOLBREEVI. Additionally, in the United Kingdom ("UK"), MOLBREEVI for the treatment of autoimmune PAP was granted Innovation Passport (June 2022) and Promising Innovative Medicine (August 2022) designations by the MHRA. These designations provide the opportunity for enhanced dialogue and input from the MHRA and the Health Technology Assessment bodies in England, Scotland, and Wales.

In 2019, we announced that IMPALA, the Phase 2/3 clinical trial of MOLBREEVI for the treatment of autoimmune PAP did not meet its primary endpoint of improvement from baseline at Week 24 compared to placebo in the alveolar-arterial gradient, or (A-a)DO 2. While the trial did not meet its primary endpoint, the totality of data from the IMPALA trial gave us confidence that MOLBREEVI had the potential to address a significant unmet need in this rare lung disease. These data include:

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multiple key secondary and exploratory endpoints that either achieved p values < 0.05 or trended in favor of the active drug arms;

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results from the open-label period of the trial that demonstrated a sustained treatment effect, or continued improvement, after longer term exposure to MOLBREEVI; additionally, patients who had been on placebo during the double-blind period of the trial and switched to treatment with MOLBREEVI during the open-label period showed improvements that eventually were generally similar to those seen in patients who received MOLBREEVI during the double-blind period; and

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MOLBREEVI being generally well tolerated, and its safety profile, when compared to placebo, was generally similar except for a few events that did not lead to discontinuations.

In September 2020, results from the IMPALA trial were published in the New England Journal of Medicine.

In June 2021, the Phase 3 IMPALA-2 pivotal trial, which built on the key learnings from the first IMPALA trial, was initiated and enrollment completed in June 2023.

In March 2024 and October 2024, respectively, the EMA and the MHRA accepted our MOLBREEVI Pediatric Investigational Plan (“PIP”) and a pediatric autoimmune PAP trial is currently ongoing.

In June 2024, we reported top line results from the pivotal IMPALA-2 trial that demonstrated significant improvement in hemoglobin adjusted gas exchange, as measured by diffusing capacity of the lungs for carbon monoxide ("DLCO") and clinical benefit, as measured by the St. George’s Respiratory Questionnaire ("SGRQ") and Exercise Capacity (“EC”) as measured by an exercise treadmill test. MOLBREEVI was well tolerated throughout the 48-Weeks and no unexpected safety signals were seen. A summary of results are as follows:

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statistically significant improvement in mean change from baseline in DLCO versus placebo at Week 24 (primary endpoint) and Week 48 (secondary endpoint), showing durability of effect;

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statistically significant improvement in mean change from baseline in SGRQ Total Score at Week 24 (secondary endpoint);

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nominally significant improvements in mean change from baseline in SGRQ Activity Score at Week 24 and Peak metabolic equivalents ("Peak METs") (an established measure of EC) at Week 48. We considered data with a p-value <0.05 to be nominally significant;

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97% of patients completed the double-blind treatment period through Week 48 with no trial drug related adverse events leading to discontinuation; and

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100% of patients that completed the 48-Week double-blind period of the trial elected to participate in the 96-Week open-label period.

In February 2024 and May 2024, respectively, the EMA and FDA conditionally accepted "MOLBREEVI" as the trade name for molgramostim inhalation solution. The MOLBREEVI trade name approval will not be finalized until molgramostim inhalation solution is approved by the respective regulatory entities.

On March 26, 2025, we announced the completion of the rolling BLA submission to the FDA and our request for Priority Review.

In May 2025, we announced the receipt of an RTF from the FDA.

In August 2025, results from the IMPALA-2 trial were published in the New England Journal of Medicine.

In November 2025, the European Patent Office ("EPO") issued patent No. 4 496 611 titled, “Drug-Device Combination Comprising a Liquid Solution and a Nebulizer for Aerosolization of the Liquid Solution” which is jointly held by Savara and PARI and covers the combination of Savara’s investigational therapy, MOLBREEVI, and PARI’s investigational eFlow® Nebulizer System that has been optimized for the delivery of MOLBREEVI. This patent covers our drug-device combination through March 2043.

In November 2025, the EPO notified Savara that it intends to grant a patent for the liquid formulation of MOLBREEVI, which, once granted, will provide protection in Europe through March 2041.

In December 2025 we resubmitted the BLA for MOLBREEVI for treatment of patients with autoimmune PAP and requested Priority Review of the application.

In February 2026 the FDA formally filed the BLA for MOLBREEVI and Priority Review granted.

Detailed Program Description

MOLBREEVI

Background on autoimmune PAP

Autoimmune pulmonary alveolar proteinosis, known as autoimmune PAP, is a specific disease belonging to a family of distinct rare lung diseases collectively referred to as PAP. Autoimmune PAP represents about 90% of all patients with PAP and the estimated diagnosed prevalence of PAP is six to seven cases per million people in the U.S., with similar or higher prevalence reported elsewhere in the world. For example, one study estimated that the diagnosed prevalence in Japan could be three to four times the estimate of six to seven cases per million.

Autoimmune PAP is characterized by the accumulation of surfactant in the alveoli, or air sacs, of the lungs. The surfactant consists of proteins and lipids and is an important physiological substance that lines the inside of the alveoli to prevent the lungs from collapsing. The lungs continuously produce new active surfactant. In a healthy lung, the surfactant is cleared by immune cells called alveolar macrophages. However, in lungs of patients with autoimmune PAP, the macrophages fail to clear the surfactant from the alveoli, leading to gradual accumulation of surfactant in the alveoli. The root cause of autoimmune PAP is an autoimmune response (auto-antibodies) against GM-CSF, a naturally occurring protein in the body. Pulmonary macrophages need to be stimulated by GM-CSF to function properly, but in autoimmune PAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering the macrophages unable to function normally, including the inability to clear surfactant from the alveoli.

Autoimmune PAP most commonly affects individuals 30-50 years of age, but people of any age can be affected. As a result of the accumulation of surfactant, gas exchange in the lungs is impaired, and patients start to experience shortness of breath, fatigue, and decreased exercise tolerance. Typically, shortness of breath is first observed upon exertion, but as the disease progresses, shortness of breath can be experienced even when a person is at rest. Patients may experience cough, sputum production, and episodes of fever, especially if secondary lung infection develops. In the long-term, the disease can lead to complications, including serious infections. Over time, autoimmune PAP can lead to pulmonary fibrosis and respiratory failure, which can be fatal and may require lung transplantation.

Current treatment options for Autoimmune PAP

In the U.S. and Europe, there are no approved medicines for the treatment of autoimmune PAP. The current therapy for autoimmune PAP is a non-standardized procedure called whole lung lavage (“WLL”), which entails washing the lungs with saline to physically remove excess surfactant from the lung. The invasive and inconvenient procedure is performed under general anesthesia and involves:

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insertion of a double-lumen endobronchial tube for lung separation;

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repeated filling of the treated lung with up to 15-50 liters of saline;

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percussion of the lung to emulsify the surfactant sediment; and

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draining the saline by gravity until the lavage fluid that is removed from the lung becomes clear.

Potential complications from WLL include rib fracture, hypoxia, pneumothorax (collapsed lung), hydrothorax (fluid in pleural cavity), superimposed infection, and acute respiratory distress syndrome ("ARDS").

WLLs are performed by highly experienced physicians at specialist sites and necessitate hospitalization. As WLL does not correct the underlying pathophysiology of the disease, nor prevent abnormal surfactant accumulation, patients who undergo the procedure may only experience temporary symptomatic relief. Once the lungs refill with surfactant, the WLL procedure may need to be repeated.

As there are no approved pharmaceutical treatments available for autoimmune PAP in the U.S. and Europe, there is an unmet need for a convenient and efficacious medicinal treatment. We believe that inhalation of MOLBREEVI activates macrophages in the alveoli, thus potentially restoring the surfactant-clearing activity of the alveolar macrophages and considerably improving oxygenation and exercise tolerance. Sargramostim (Leukine), an injectable form of GM-CSF, is approved in the U.S. for intravenous and subcutaneous administration treatment of neutropenia caused by cancer chemotherapy and other related indications. In April 2024, sargramostim was approved in Japan for the treatment of autoimmune PAP. Currently, there are no approved inhalation formulations of GM-CSF in the U.S. or Europe, nor are there any investigational drugs in clinical development for autoimmune PAP in the U.S. or Europe, other than MOLBREEVI.

The potential benefits of inhaled GM-CSF in autoimmune PAP have prompted independent clinicians and academic researchers in the U.S., Japan, and countries in Europe to study the safety and efficacy of inhaled GM-CSF in autoimmune PAP patients. In addition to our two placebo-controlled clinical trials of MOLBREEVI in this patient population—the Phase 2/3 IMPALA trial (n=138) and the Phase 3 IMPALA-2 trial, the largest placebo-controlled trial in autoimmune PAP (n=164)—several investigator-sponsored, open-label clinical trials and case studies of inhaled GM-CSF treatment have been published, with promising results on the efficacy and safety of the treatment. In total, treatment of nearly 150 autoimmune PAP patients with inhaled GM-CSF has been reported in open-label trials or retrospective cohorts, as well as several individual case reports. A case series published in ERJ Open Research in January 2025 retrospectively evaluated 5 autoimmune PAP patients who received molgramostim through European single-patient access supplied by Savara. Following treatment with molgramostim (mean duration of 4.2 years), the real-world outcomes data suggest molgramostim addresses the underlying pathophysiology of autoimmune PAP, resulting in improved lung function, decreased disease burden, restored patient functionality, reduced clinical symptoms, and, at the time of publication, no need for WLL. For details on the results of the IMPALA-2 trial, please see the Clinical Development of MOLBREEVI – autoimmune PAP: Phase 3 IMPALA-2 Trial section included in this report.

According to our review of published literature, few safety issues related to GM-CSF inhalation in patients with autoimmune PAP have been reported. However, there is still limited information available on the long-term safety of inhaled GM-CSF.

Product Description

MOLBREEVI is an inhaled formulation of a non-glycosylated recombinant human GM-CSF that we are developing for the treatment of autoimmune PAP. GM-CSF is an endogenous growth factor that stimulates the proliferation and differentiation of hematopoietic cells (blood immune cells), mainly granulocytic and monocytic cells, which defend against bacteria and viruses, and clear cellular debris and waste substances from the body. MOLBREEVI is produced in a strain of Escherichia coli bearing a genetically engineered plasmid containing a human GM-CSF gene.

Our product is a drug-device combination consisting of molgramostim (drug component) and a vibrating mesh nebulizer (device component). MOLBREEVI is supplied as a sterile formulation containing 300 µg of molgramostim in 1.2 mL solution. MOLBREEVI is administered once daily by inhalation via a high efficiency nebulizer, the investigational, proprietary eFlow® Nebulizer System (PARI Pharma GmbH). The eFlow®Nebulizer System is a reusable electronic inhalation system that has been optimized for administration of molgramostim. The eFlow® consists of a controller unit (AC or battery powered), a nebulizer handset, and a connection cord. The controller unit's lifespan is multiple years, and the handset is replaced monthly.

MOLBREEVI was granted Orphan Drug Designation by the FDA in October 2012 and by the EMA in July 2013 for the treatment of autoimmune PAP. It was also granted Fast Track Designation and BTD by the FDA in May 2019 and

December 2019, respectively. Further, it was granted Innovation Passport (June 2022) and Promising Innovative Medicine (August 2022) designations in the UK. Since 2014, molgramostim has been available in several European countries for the treatment of autoimmune PAP for named patients following unsolicited physician requests. In September 2024, we launched the Savara Expanded Access Program ("EAP") for molgramostim in patients with autoimmune PAP. The program enables physicians to request molgramostim for eligible patients in select geographies where the product is not commercially available and in compliance with local regulatory requirements. The Savara EAP has been reviewed and allowed to proceed by the FDA and is open for requests from physicians, on behalf of autoimmune PAP patients, in select countries in North America and Europe. More information can be found on the program at www.clinicaltrials.gov, NCT06546098.

We anticipate that, if approved, MOLBREEVI will be used as a long-term treatment in patients with autoimmune PAP. There are no data yet to support the long-term benefits of inhaled GM-CSF. However, in the real-world case studies (n=5) published in ERJ Open Research, noted above, none of the five patients required WLL after >1 year on molgramostim, suggesting that molgramostim therapy may have prevented the need for WLL in these patients.

MOLBREEVI Key Advantages

Based on data from the completed Phase 2/3 IMPALA trial and the pivotal Phase 3 IMPALA-2 trial and building upon the published investigator-sponsored treatment experience with inhaled GM-CSF, we believe MOLBREEVI has the potential to become the treatment of choice for autoimmune PAP. The following characteristics of MOLBREEVI may contribute to the clinical profile of the investigational product candidate, as well as facilitate potential regulatory approval and successful commercialization.

Specifically, MOLBREEVI offers:

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a strong product foundation that applies both a previously approved active drug substance class and drug delivery technology;

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GM-CSF delivered directly to the lungs, the primary site of macrophage dysfunction in autoimmune PAP, which could result in clinical efficacy with limited systemic adverse effects;

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a portable nebulizer system that provides a fast and convenient method of administration (nebulization time of about 3 to 5 minutes each day); this is highly desirable for long-term treatment in a chronic disease, such as autoimmune PAP;

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eligibility for strong market protection via orphan drug status, potential eligibility for biologic exclusivity that provides twelve years of total market protection in the U.S.;

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a proprietary cell bank used in the production of the drug substance; and

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an exclusive agreement for the drug delivery device that is optimized for administration of MOLBREEVI.