LANGHORNE, Pa.--(BUSINESS WIRE)--Savara Inc. (Nasdaq: SVRA) (the Company), a clinical stage biopharmaceutical company focused on rare respiratory diseases, today announced positive results from the pivotal, Phase 3 IMPALA-2 clinical trial. IMPALA-2 is a 48-week, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of molgramostim 300 mcg administered once daily by inhalation with matching placebo in adult patients with aPAP (NCT04544293).

宾夕法尼亚州兰格霍恩（商业新闻短讯）--Savara Inc.（纳斯达克：SVRA）（该公司）是一家专注于罕见呼吸道疾病的临床阶段生物制药公司，今天宣布了关键的IMPALA-2期临床试验的积极结果。IMPALA-2是一项为期48周的随机双盲安慰剂对照试验，评估了成年aPAP患者每天一次吸入匹配安慰剂的莫格司亭300 mcg的疗效和安全性（NCT04544293）。

Molgramostim is an inhaled form of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)..

Molgramostim是重组人粒细胞巨噬细胞集落刺激因子（GM-CSF）的吸入形式。。

The trial met its primary endpoint. The treatment difference between molgramostim and placebo for mean change from baseline to Week 24 in hemoglobin-adjusted percent predicted DLCO achieved statistical significance. This statistically significant treatment difference was sustained at Week 48, a secondary endpoint, which demonstrated durability of effect..

该试验达到了其主要终点。molgramostim和安慰剂之间血红蛋白调整百分比预测DLCO从基线到第24周的平均变化的治疗差异具有统计学意义。这种统计学上显着的治疗差异在第48周持续存在，这是次要终点，证明了效果的持久性。。

The treatment difference between molgramostim and placebo for mean change from baseline to Week 24 in SGRQ Total Score achieved statistical significance. Two additional secondary endpoints reached nominal significance: SGRQ Activity Score at Week 24 and exercise capacity using a treadmill test at Week 48..

molgramostim和安慰剂在SGRQ总分中从基线到第24周的平均变化的治疗差异达到统计学显着性。另外两个次要终点达到了名义上的显着性：第24周的SGRQ活动评分和第48周使用跑步机测试的运动能力。。

“There is a high unmet need for effective, disease-specific pharmacotherapy for autoimmune PAP,” said Bruce Trapnell, M.D., Professor of Medicine and Pediatrics at the University of Cincinnati College of Medicine and the Lead Clinical Investigator of the IMPALA-2 trial. “Patients typically experience breathlessness, which begins slowly and progresses over time, often accompanied by cough and fatigue, and in some patients, serious infections, pulmonary fibrosis, and respiratory failure requiring lung transplantation.

辛辛那提大学医学院医学和儿科教授、IMPALA-2试验首席临床研究者、医学博士布鲁斯·特拉普内尔（BruceTrapnell）说：“对于自身免疫性巴氏肺动脉高压的有效的、针对疾病的药物治疗，目前仍有很高的需求尚未得到满足。”。“患者通常会出现呼吸困难，呼吸困难开始缓慢并随着时间的推移而发展，通常伴有咳嗽和疲劳，在某些患者中，严重感染，肺纤维化和需要肺移植的呼吸衰竭。

With convincing data from two large clinical trials, the evidence now clearly demonstrates molgramostim has the potential to be a safe and efficacious treatment option for these patients. This is a momentous day for the aPAP community.”.

有了来自两项大型临床试验的令人信服的数据，现在的证据清楚地表明，molgramostim有可能成为这些患者安全有效的治疗选择。对于aPAP社区来说，这是一个重要的日子。”。

IMPALA-2 Top Line Efficacy Results (Full Analysis Set, n=164):

IMPALA-2一线疗效结果（完整分析集，n=164）：

Lung Function Efficacy Endpoints

肺功能疗效终点

Molgramostim 300 mcg meanchange from baseline compared toplacebo

P-value

P值

Primary: DLCO % predicted (Hgb-adjusted) at Week 24

主要：在第24周预测DLCO%（经Hgb调整）

6.00

6.00

0.0007

0.0007

Secondary: DLCO % predicted (Hgb-adjusted) at Week 48

次要：第48周预测DLCO%（Hgb调整）

6.90

6.90

0.0008

0.0008

Secondary Efficacy Endpoints Measuring Clinical Benefit

衡量临床效益的次要疗效终点

Molgramostim 300 mcg meanchange from baseline to Week 24compared to placebo

与安慰剂相比，Molgramostim 300 mcg意味着从基线到第24周的变化

P-value

P值

Molgramostim 300 mcg meanchange from baseline to Week48 compared to placebo

与安慰剂相比，Molgramostim 300 mcg意味着从基线到第48周的变化

P-value

P值

SGRQ Total Score (points)

SGRQ总分（分）

-6.59

-6.59

0.0072

0.0072

-4.87

-4.87

0.1046

0.1046

SGRQ Activity Score (points)

SGRQ活动得分（分）

-7.81

-7.81

0.0149

0.0149

-5.99

-5.99

0.1216

0.1216

Exercise Capacity (peak METs)

运动能力（峰值代谢综合征）

0.41

0.41

0.0845

0.0845

0.55

0.55

0.0234

0.0234

SGRQ is a patient-reported outcomes instrument that measures overall health, daily life, and a patient’s perceived well-being. SGRQ Activity assesses the patient’s ability to carry out daily physical activity. With SGRQ, a negative change from baseline corresponds to improvement. Exercise capacity as measured by a treadmill is a cardiorespiratory health (CRH) measurement..

SGRQ是一种患者报告的结果工具，用于测量整体健康，日常生活和患者感知的幸福感。SGRQ活动评估患者进行日常体育活动的能力。对于SGRQ，相对于基线的负面变化对应于改进。跑步机测量的运动能力是一种心肺健康（CRH）测量。。

Molgramostim was well tolerated. The frequency of adverse events was generally similar between treatment groups. Two patients (2.5%) discontinued molgramostim treatment due to adverse events, both of which were considered unrelated to trial drug. The most commonly reported adverse events in the molgramostim group were COVID-19, cough, and pyrexia, with COVID-19 occurring more frequently with molgramostim than with placebo..

Molgramostim耐受性良好。治疗组之间不良事件的频率通常相似。由于不良事件，两名患者（2.5%）停止了莫格司汀治疗，两者均被认为与试验药物无关。molgramostim组最常报告的不良事件是COVID-19，咳嗽和发热，molgramostim比安慰剂更常发生COVID-19。。

IMPALA-2 Top Line Safety Results (Safety Analysis Set, n=164):

IMPALA-2顶级安全结果（安全分析集，n=164）：

Treatment Related Adverse Events

治疗相关不良事件

Molgramostim(N=81)n (%)

莫氏菌病（N=81）N（%）

Placebo(N=83)n (%)

安慰剂（N=83）N（%）

Any

任何

69 (85)

69 (85)

71 (86)

71 (86)

Most common

最常见

COVID-19

新型冠状病毒肺炎

18 (22)

18 (22)

8 (10)

8 (10)

Cough

咳嗽

17 (21)

17 (21)

18 (22)

18 (22)

Pyrexia

发热

11 (14)

11 (14)

9 (11)

9 (11)

Nasopharyngitis

鼻咽炎

11 (14)

11 (14)

7 (8)

7 (8)

Arthralgia

关节痛

9 (11)

9 (11)

7 (8)

7 (8)

Headache

头痛

9 (11)

9 (11)

7 (8)

7 (8)

Diarrhea

腹泻

9 (11)

9 (11)

2 (2)

2 (2)

Alveolar proteinosis

肺泡蛋白沉积

4 (5)

4 (5)

12 (14)

12 (14)

Serious

严重

14 (17)

14 (17)

20 (24)

20 (24)

Treatment related

治疗相关

20 (25)

20 (25)

16 (19)

16 (19)

“The IMPALA-2 results not only met, but exceeded, our expectations, validating our hypothesis that molgramostim provides clear, durable improvement in gas exchange, and beyond that, clinical benefits that positively impact quality of life for aPAP patients,' said Matt Pauls, Chair and CEO, Savara. 'The strong efficacy data and favorable benefit-risk profile potentially position molgramostim to be the first and only approved therapeutic for aPAP in the U.S.

萨瓦拉主席兼首席执行官马特·保尔斯（Matt Pauls）说：“IMPALA-2的结果不仅达到了我们的预期，而且超过了我们的预期，验证了我们的假设，即molgramostim在气体交换方面提供了明显，持久的改善，除此之外，临床益处对aPAP患者的生活质量产生了积极影响。强大的疗效数据和有利的利益风险概况可能使molgramostim成为美国第一个也是唯一被批准的aPAP治疗剂。

and Europe. We extend our gratitude to the patients and their families, clinicians, and site personnel for their contributions and ongoing participation in the largest clinical trial in aPAP. We look forward to analyzing the full data from IMPALA-2 and anticipate submitting it for presentation at a scientific conference later this year.”.

和欧洲。我们感谢患者及其家属，临床医生和现场人员的贡献，并持续参与aPAP最大的临床试验。我们期待着分析IMPALA-2的完整数据，并预计在今年晚些时候的科学会议上提交。”。

Molgramostim has been granted Orphan Drug, Fast Track, and Breakthrough Therapy designation from the U.S. Food and Drug Administration, Orphan Drug designation from the European Medicines Agency and Innovative Passport and Promising Innovative Medicine designation from the UK's Medicines and Healthcare Products Regulatory Agency for the treatment of aPAP..

Molgramostim已被美国食品和药物管理局授予孤儿药、快速通道和突破性治疗指定，欧洲药品管理局授予孤儿药指定，英国药品和保健品监管局授予创新护照和有希望的创新药物指定，用于治疗aPAP。。

Conference Call

电话会议

Savara management will host a conference call and live audiovisual webcast to discuss the IMPALA-2 results at 8:00am ET today. To access the live webcast of the call with slides please click here or visit the 'Events & Presentations' section of Savara’s website. To access the call by phone, please use this registration link, and you will be provided with dial in details.

萨瓦拉管理层将于美国东部时间今天上午8:00主持电话会议和现场视听网络广播，讨论IMPALA-2的结果。要通过幻灯片访问电话的在线直播，请单击此处或访问萨瓦拉网站的“活动与演示”部分。要通过电话访问呼叫，请使用此注册链接，您将获得拨号详细信息。

A replay of the webcast will be available approximately 24 hours after the conclusion of the call and archived for 90 days under the 'Events & Presentations' section of the Company's website at www.savarapharma.com..

网络广播的重播将在通话结束后约24小时提供，并在公司网站www.savarapharma.com的“活动与演示”部分存档90天。。

About the IMPALA-2 Trial

关于IMPALA-2试验

IMPALA-2 is a global, pivotal, Phase 3, 48-week, randomized, double-blind, placebo-controlled clinical trial designed to compare the efficacy and safety of molgramostim 300 mcg administered once daily by inhalation with matching placebo in patients with aPAP. The trial is being conducted at 43 clinical trial sites across 16 countries in the U.S., Canada, Japan, South Korea, Australia and countries in Europe, including Turkey.

IMPALA-2是一项全球性，关键性的3期48周随机双盲安慰剂对照临床试验，旨在比较aPAP患者每天一次吸入与匹配安慰剂的莫格司亭300 mcg的疗效和安全性。该试验正在美国、加拿大、日本、韩国、澳大利亚和包括土耳其在内的欧洲16个国家的43个临床试验地点进行。

The primary efficacy assessment is diffusing capacity of the lungs for carbon monoxide (DLCO), a gas exchange measure, and the primary endpoint is change from baseline to Week 24 in percent predicted DLCO, with a secondary endpoint of change from baseline to Week 48 in percent predicted DLCO. Three additional secondary efficacy variables evaluate clinical measures of direct patient benefit: St.

主要疗效评估是肺部对一氧化碳（DLCO）的扩散能力，这是一种气体交换测量，主要终点是从基线到第24周的变化（预测DLCO的百分比），次要终点是从基线到第48周的变化（预测DLCO的百分比）。另外三个次要疗效变量评估直接患者获益的临床指标：St。

George’s Respiratory Questionnaire (SGRQ) Total Score, SGRQ Activity Score, and exercise capacity using a treadmill test, with each endpoint measured at Weeks 24 and 48. The primary time point for efficacy assessments is at Week 24; however, efficacy was assessed through Week 48 to evaluate durability of effect.

乔治的呼吸问卷（SGRQ）总分，SGRQ活动评分和使用跑步机测试的运动能力，每个终点在第24周和第48周测量。疗效评估的主要时间点是第24周；然而，在第48周评估疗效以评估效果的持久性。

Safety was assessed through Week 48. Pending applicable regulatory and ethics committee approvals, following the 48-week double-blind treatment period patients may continue in a 96-week open-label period and receive molgramostim 300 mcg administered once daily..

在第48周评估安全性。在获得适用的监管和道德委员会批准之前，在48周的双盲治疗期后，患者可以在96周的开放标签期内继续服用，并每天服用一次molgramostim 300 mcg。。

About aPAP

关于aPAP

Autoimmune PAP is a rare lung disease characterized by the abnormal build-up of surfactant in the alveoli (or air sacs) of the lungs. Surfactant consists of proteins and lipids and is an important physiological substance that lines the alveoli to prevent them from collapsing. In a healthy lung, excess surfactant is cleared and digested by immune cells called alveolar macrophages.

。表面活性剂由蛋白质和脂质组成，是一种重要的生理物质，排列在肺泡上以防止其塌陷。在健康的肺中，过量的表面活性剂被称为肺泡巨噬细胞的免疫细胞清除和消化。

Alveolar macrophages need to be stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) to function properly in clearing surfactant, but in autoimmune PAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering the macrophages unable to adequately clear surfactant. As a result, an excess of surfactant accumulates in the alveoli, causing impaired gas exchange, resulting in clinical symptoms of shortness of breath, often with cough and frequent fatigue.

肺泡巨噬细胞需要被粒细胞巨噬细胞集落刺激因子（GM-CSF）刺激才能正常清除表面活性剂，但在自身免疫性PAP中，GM-CSF被抗GM-CSF的抗体中和，使巨噬细胞无法充分清除表面活性剂。因此，过量的表面活性剂积聚在肺泡中，导致气体交换受损，导致呼吸急促的临床症状，通常伴有咳嗽和频繁疲劳。

Patients may also experience episodes of fever, chest pain, or coughing up blood, especially if secondary lung infection develops. In the long-term, the disease can lead to serious complications, including lung fibrosis and the need for a lung transplant..

。从长远来看，这种疾病可能导致严重的并发症，包括肺纤维化和需要进行肺移植。。

About Savara

关于萨瓦拉

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) specifically developed for inhalation of a large molecule.

Savara是一家临床阶段的生物制药公司，专注于罕见的呼吸道疾病。我们的主要项目molgramostim雾化器溶液是一种吸入性粒细胞巨噬细胞集落刺激因子（GM-CSF），处于自身免疫性肺泡蛋白沉着症（aPAP）的3期发展中。Molgramostim是通过专门为吸入大分子而开发的研究性eFlow®雾化器系统（PARI Pharma GmbH）提供的。

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 www.savarapharma.com. (X, formerly known as Twitter: @SavaraPharma, LinkedIn: www.linkedin.com/company/savara-pharmaceuticals/)..

我们的管理团队在罕见呼吸系统疾病和肺部医学方面具有丰富的经验，可以识别未满足的需求，并有效地推动候选产品获得批准和商业化。更多信息可以在www.savarapharma.com上找到。（X，以前称为推特：@savarapharma，LinkedIn:www.LinkedIn.com/company/savara pharmaceuticals/）。。

Forward-Looking Statements

前瞻性声明

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.

萨瓦拉提醒您，本新闻稿中的声明并非对历史事实的描述，而是1995年《私人证券诉讼改革法案》所指的前瞻性声明。前瞻性陈述可以通过使用引用未来事件或情况的词语来识别，例如“预期”、“打算”、“计划”、“预期”、“相信”和“将会”等。

Such statements include, but are not limited to, statements related to the anticipated timing of the submission of a Biologics License Application; that there is a high unmet need in aPAP for a pharmacotherapy; that the evidence now clearly demonstrates molgramostim has the potential to be a safe and efficacious treatment option for aPAP patients; statements regarding the therapeutic benefits of molgramostim in aPAP and the impact of molgramostim on quality of life for aPAP patients; that the strong efficacy data and favorable benefit-risk profile potentially position molgramostim to be the first and only approved therapeutic for aPAP in the U.S.

此类声明包括但不限于与提交生物制剂许可证申请的预期时间有关的声明；aPAP对药物治疗的需求尚未得到满足；现在的证据清楚地表明，molgramostim有可能成为aPAP患者安全有效的治疗选择；关于molgramostim在aPAP中的治疗益处以及molgramostim对aPAP患者生活质量的影响的声明；强大的疗效数据和有利的利益风险概况可能使molgramostim成为美国第一个也是唯一被批准的aPAP治疗药物。

and Europe; and that Savara anticipates submitting the full data from IMPALA-2 for presentation at a scientific conference later this year. 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.

和欧洲；萨瓦拉预计将在今年晚些时候的科学会议上提交IMPALA-2的完整数据。萨瓦拉可能无法实际实现此类前瞻性声明中提及的任何事项，您不应过度依赖这些前瞻性声明。

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 that analysis of the full data set from the IMPAL.

这些前瞻性陈述基于萨瓦拉目前的预期，并涉及可能永远不会实现或可能被证明是不正确的假设。由于各种风险和不确定性，实际结果和事件发生的时间可能与此类前瞻性声明中的预期有很大差异，其中包括但不限于分析IMPAL完整数据集的风险。