Pulmonary Alveolar Proteinosis

Remains On-Track to Report Top Line Data from the Pivotal Phase 3 IMPALA-2 Trial by End of 2Q 2024 48-week placebo-controlled trial is evaluating molgramostim nebulizer solution (molgramostim), a novel inhaled biologic, for the treatment of autoimmune Pulmonary Alveolar Proteinosis (aPAP), a rare lung disease Anticipate Filing Biologics License Application (BLA) in 1H 2025, Pending Outcome of IMPALA-2 Trial With ~$162M in Cash and Short-term Investments, Company Believes it is Sufficiently Capitalized into 2026 LANGHORNE, Pa.--(BUSINESS WIRE)-- Savara Inc. (Nasdaq: SVRA) (the Company), a clinical stage biopharmaceutical company focused on rare respiratory diseases, reported financial results for the fourth quarter and full year ending December 31, 2023 and provided a business update. “We look forward to reporting IMPALA-2 top line results at the end of the second quarter and, assuming positive data, anticipate filing the BLA in the first half of 2025,” said Matt Pauls, Chair and CEO, Savara. “2023 was a year of strong execution that included the on-time, over-enrollment of the Phase 3 IMPALA-2 trial and an analysis of a health claims database that identified ~3,600 currently diagnosed aPAP patients and another ~1,400 potential, currently undiagnosed, aPAP patients in the U.S. Additionally, we launched aPAP ClearPathTM, a simple, accurate, no-cost, lab-developed GM-CSF autoantibody blood test, along with a disease state awareness campaign, that is educating U.S. pulmonologists about the disease and need for earlier testing. Finally, we completed an $80 million equity financing last July, and with $162 million in cash and investments and a track record of strong fiscal discipline, we believe we are capitalized into 2026.” Fourth Quarter Financial Results (Unaudited) Savara’s net loss for the fourth quarter of 2023 was $16.1 million, or $(0.09) per share, compared with a net loss of $10.3 million, or $(0.07) per share, for the fourth quarter of 2022. Research and development expenses for the fourth quarter of 2023 and 2022 were $12.7 million and $7.6 million, respectively. General and administrative expenses for the fourth quarter of 2023 and 2022 were $4.9 million and $3.2 million, respectively. As of December 31, 2023, the Company had cash, cash equivalents and short-term investments of $162.3 million. Fiscal Year 2023 Financial Results The Company’s net loss for the year ended December 31, 2023 was $54.7 million, or $(0.33) per share, compared with a net loss of $38.2 million, or $(0.25) per share for the year ended December 31, 2022. Research and development expenses increased $16.4 million, or 58.8%, to $44.3 million for the year ended December 31, 2023 from $27.9 million for the year ended December 31, 2022. This increase was primarily due to the performance of tasks related to our molgramostim program which includes approximately $6.8 million of costs related to our chemistry, manufacturing, and controls activities, $4.4 million of costs related to our IMPALA-2 trial, including CRO-related activities, $1.6 million of costs related to quality assurance, and $3.6 million due to an increase in personnel and related costs. General and administrative expenses increased $4.7 million, or 43.4%, to $15.7 million for the year ended December 31, 2023 from $10.9 million for the year ended December 31, 2022. Approximately $3.6 million of this was primarily attributable to the addition of key personnel to facilitate the management of our business and $1.1 million was attributable to certain commercial activities. About Savara Savara is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, molgramostim nebulizer solution, is an inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (aPAP). Molgramostim is delivered via an investigational eFlow® Nebulizer System (PARI Pharma GmbH). Our management team has significant experience in rare respiratory diseases and pulmonary medicine, identifying unmet needs, and effectively advancing product candidates to approval and commercialization. More information can be found at . (X, formerly known as Twitter: @SavaraPharma, LinkedIn: ). Forward-Looking Statements Savara cautions you that statements in this press release that are not a description of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others. Such statements include, but are not limited to, statements related to the expected timing of reporting top line data from the IMPALA-2 trial, the anticipated timing of the BLA filing, the number of potential aPAP patients, and our belief the Company is capitalized into 2026. Savara may not actually achieve any of the matters referred to in such forward-looking statements, and you should not place undue reliance on these forward-looking statements. These forward-looking statements are based upon Savara’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risks and uncertainties relating to the impact of widespread health concerns impacting healthcare providers or patients, disruptions or inefficiencies in the supply chain and geopolitical conditions, the outcome of our ongoing and planned clinical trials for our product candidate, the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient resources for Savara’s operations and to conduct or continue planned clinical development programs, the ability to successfully develop our product candidate, the risks associated with the process of developing, obtaining regulatory approval for and commercializing drug candidates such as molgramostim that are safe and effective for use as human therapeutics, and the timing and ability of Savara to raise additional capital as needed to fund continued operations. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. For a detailed description of our risks and uncertainties, you are encouraged to review our documents filed with the SEC including our recent filings on Form 8-K, Form 10-K and Form 10-Q. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Savara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as may be required by law. Financial Information to Follow Savara Inc. and Subsidiaries Consolidated Statements of Operations and Comprehensive Loss (in thousands, except for share and per share amounts) (Unaudited) Three months ended Twelve months ended December 31, December 31, 2023 2022 2023 2022 Operating expenses: Research and development $ 12,746 $ 7,626 $ 44,262 $ 27,879 General and administrative 4,852 3,242 15,668 10,929 Depreciation and amortization 32 7 77 31 Total operating expenses 17,630 10,875 60,007 38,839 Loss from operations (17,630 ) (10,875 ) (60,007 ) (38,839 ) Other income (expense), net: 1,531 575 5,309 689 Net loss attributable to common stockholders $ (16,099 ) $ (10,300 ) $ (54,698 ) $ (38,150 ) Net loss per share - basic and diluted $ (0.09 ) $ (0.07 ) $ (0.33 ) $ (0.25 ) Weighted average shares - basic and diluted 179,843,515 152,773,739 165,204,652 152,771,817 Other comprehensive (loss) gain 671 1,002 334 (610 ) Total comprehensive loss $ (15,428 ) $ (9,298 ) $ (54,364 ) $ (38,760 ) Savara Inc. and Subsidiaries Consolidated Balance Sheet Data (in thousands) December 31, December 31, 2023 2022 Cash, cash equivalents, and short-term investments $ 162,319 $ 125,876 Working capital 155,350 123,087 Total assets 177,564 139,777 Total liabilities 37,192 31,999 Stockholders’ equity: 140,372 107,778

LANGHORNE, Pa.--(BUSINESS WIRE)-- Savara Inc. (Nasdaq: SVRA), a clinical stage biopharmaceutical company focused on rare respiratory diseases, today announced that its management team will participate in a fireside chat at the Barclays 26th Annual Global Healthcare Conference on March 14, 2024 at 5:00am PT/8:00am ET. A live webcast of the fireside chat will be available on Savara’s website at and will be archived for 90 days. About Savara Savara is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, molgramostim nebulizer solution, is an inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (aPAP). Molgramostim is delivered via an investigational eFlow® Nebulizer System (PARI Pharma GmbH). Our management team has significant experience in rare respiratory diseases and pulmonary medicine, identifying unmet needs, and effectively advancing product candidates to approval and commercialization. More information can be found at . (X, formerly known as Twitter: @SavaraPharma, LinkedIn: ).

The absence of a single immune cell receptor has been linked to both fewer defenses against mycobacterial infections, such as TB, and damaging buildup of sticky residue in the lungs. The macrophage is one of the body's most important inhabitants. Meaning "big eater" in Greek, this immune cell consumes and digests problematic elements from microbes and cancer cells to dust and debris. Macrophages are especially important in the lungs, where they both fight bacterial infection and clear the lungs of excess surfactant, a protein- and lipid-rich layer that's essential to healthy function but can create a sticky buildup if not controlled. In a recent study, investigators from Rockefeller University and other institutions have discovered a never-before-documented genetic disorder that causes the improper functioning of these cells. The researchers made their discovery by drawing an unexpected connection between a select group of sick children. Throughout their lives, these nine children had battled severe diseases such as pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent bacterial and viral infections that left them gasping for breath from often cyst-plagued lungs. But as genomic data revealed, the children shared another characteristic: the absence of a chemical receptor that is supposed to call alveolar macrophages into action. It's the first time that this missing receptor, called CCR2, has been linked to disease. The researchers, including Rockefeller's Jean-Laurent Casanova and Institut Imagine's Anna-Lena Neehus, recently published their results in Cell. The study also found that the children are missing half of their alveolar macrophages, which are located in the air sacs of the lungs. "It was surprising to find that CCR2 is so essential for alveolar macrophages to properly function," says Casanova. "When it comes to lung defense and cleanup, people without it are operating at a double loss." Chemical communication More formally known as C-C motif chemokine receptor 2, CCR2 sits on the surface of alveolar macrophages, a kind of monocyte (or white blood cell). It responds to the presence of a chemical ligand, or binding molecule, known as CCL-2, which is also expressed by monocytes. The receptor and ligand work together to summon macrophages to the site of an infection, and to maintain the appropriate level of surfactant; too little can lead to collapsed lung tissue, and too much can result in narrowed airways. It was among these immune cells that first author Neehus, of Casanova's lab at the Institut Imagine in Paris, was seeking evidence of genetic deficiencies that might alter their behavior. While combing through the genomic data on 15,000 patients in a database, she found two Algerian sisters, then aged 13 and 10, who'd been diagnosed with severe PAP, a syndrome in which surfactant builds up and the gas exchange that takes place in alveoli is hindered. About 90% of PAP cases are caused by antibodies that cripple a protein that stimulates the growth of infection-fighting white blood cells. The girls, however, didn't have the PAP autoantibodies. Instead, they had no CCR2 -- a newly identified genetic mutation. Perhaps its lack was connected to their pulmonary conditions, Neehus thought. "It looked interesting and promising," she recalls. She soon found seven other children in the cohort who had the same CCR2 mutation and serious lung conditions: two more pairs of siblings, and one trio of siblings. They were from the United States and Iran. Diminished capacity To explore the impact the variant might have on the children, the researchers analyzed the children's clinical histories, lung tissue samples, and genetic data. Several key findings emerged. "First we discovered that these patients have only half the normal counts of pulmonary alveolar macrophages, which explains the different types of lesions they have across the pulmonary tissues," says Casanova. With only half a crew, the reduced cleanup unit couldn't keep up with its workload, leading to tissue injury. The macrophages were otherwise normal, as were the children's other immune cells. Without CCR2 signaling, monocytes have no idea where they're needed. In the study, a live-imaging analysis of the monocytes from the lungs of a 10-year-old girl with CCR2 deficiency showed the cells milling about aimlessly, unsure where to go. (See gif at top.) In contrast, live imaging of monocytes from a healthy control patient shows them migrating in the same direction, summoned by the teamwork of CCR2 and CCL-2. A troubled inheritance This directionlessness also makes those with a CCR2 deficiency more susceptible to mycobacterial infections, because the macrophages can't find their way to the tissue clusters where mycobacteria take up residence, and thus digest the invaders. This had dire effects for three of the children in the study, who developed bacterial infections after being vaccinated with a live-attenuated substrain of Mycobacterium bovis, an agent of tuberculosis. Their immune systems failed to assemble a legion of macrophages at the vaccination site in the shoulder, causing tissue destruction or hard nodes that had to be surgically removed, or lymph node infections. (All of the children were effectively treated with antibiotics.) The children inherited the deficiency from their parents -- and yet their parents were healthy. "Each of the parents carries one disease copy of the gene, and both parents gave the affected copy to their children," says Neehus. "The parents aren't affected because they each only have one copy, whereas the kids have two." Several children were the result of consanguineous marriages, in which the parents are related. The offspring of such pairings have a higher risk of inheriting the mutation that causes CCR2 to disappear. The diagnostic test The absence of CCR2 leads to another effect: an excess of the chemokine CCL-2. Lacking its receptor, CCL-2 builds up in the blood and plasma. This outcome may provide a diagnostic test for screening patients with unexplained lung or mycobacterial disease; the detection of high CCL-2 levels could provide some clarity about the condition's genetic underpinnings. In future research, Casanova and his team will mine their database of genomes for patients with gene mutations in CCL-2 rather than in its receptor, CCR2, to understand how such errors may influence the development of disease. Neehus says, "With more follow-up studies, we could potentially cure the patients by using gene therapy to correct the mutation."