COMPOSITIONS AND METHODS FOR TREATING LUNG INJURY OR ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) CROSS REFERENCE [0001] This application claims priority to U.S. Provisional Patent Application No. 63/008,281, filed Apr.10, 2020, the entireties of which are incorporated herein by reference. SEQUENCE LISTING [0002] This application includes a sequence listing in computer readable form in a file named Roivant Sciences GmbH_ST25-3-17-2021.txt created on March 17, 2021 (12Kbytes), which is incorporated by reference herein. FIELD [0003] The present disclosure relates to therapeutic treatments for lung injury or acute respiratory distress syndrome (“ARDS”) secondary to sepsis (bacterial or viral) or any related inflammatory or immune response, including coronavirus disease 2019 (COVID-19). In particular, the present disclosure relates to methods comprising administering a granulocyte macrophage-colony stimulating factor (GM-CSF) antagonist, e.g., an anti-GM-CSF antibody or antigen-binding protein to a subject in need thereof. BACKGROUND [0004] In December 2019, the city of Wuhan, China experienced an outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 2020, COVID-19 exploded into a global pandemic (World Health Organization (WHO) COVID-19 Situation Report, 2020 at https://www.who.int/emergencies/diseases/novel-coronavirus-2 019/situation-reports) with a much higher morbidity and mortality than other commonly circulating viruses. Currently, no approved agents exist to effectively treat COVID-19 associated lung injury or ARDS. [0005] Although the current data indicate that most SARS-CoV-2 infections result in only mild symptoms for the patient, approximately 20% of COVID-19 patients experience severe viral pneumonia that can progress to ARDS and death (Wu and McGoogan, JAMA. 2020. doi:10.1001/jama.2020.2648). Based on emerging data as well as evidence from previous coronavirus epidemics, a three-phase clinical staging model has been proposed for COVID-19: (1) stage I (viral response phase)―a patient experiences fever, cough, and other systemic symptoms accompanied by an increase in viral load; (2) stage II (pulmonary phase)―the patient suffers severe pneumonia that persists, despite a decline in viral load, due to a hyperactive immune response consisting of cytokine storm and significant macrophage/neutrophil lung infiltration; and, (3) stage III (hyperinflammation phase)―the patient experiences pulmonary destruction and death (Lam et al., Clin. Biochem. Rev. 2004;25(2):121-132; Channappanavar et al., Semin. Immunopathol.2017;39(5):529-539; Liao et al., Pre-Print. 2020. https://doi.org/10.1101/2020.02.23.20026690; Mehta et al., Lancet. 2020. doi:10.1016/S0140-6736(20)30628-0; Siddiqi HK, Mehra MR. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. J Heart Lung Transplant.2020. doi:10.1016/j.healun.2020.03.012 (Siddiqi, 2020). See also Figure 20. [0006] GM-CSF, a myeloid cell growth factor and pro-inflammatory cytokine has been proposed as a key mediator of COVID-19 hyperinflammation. In open-label COVID-19 studies, treatment with monoclonal antibodies against GM-CSF or its receptor has been correlated with decreased mortality and improvement in other key clinical outcomes. [De Luca 2020 Lancet Rheumatology; Temesgen 2020 Mayo Clinic Proceedings]. Preclinical studies in mouse models with pathologies similar to late-stage COVID-19, including cytokine release syndrome, sepsis, and acute lung injury, have also demonstrated benefit with GM-CSF inhibition. [Lang 2020 Nat Rev Immunol; Mehta 2020 Lancet Respir Med]. To date, several large randomized controlled trials are ongoing or have reported topline results. Targeting GM- CSF thus represents a promising therapeutic strategy for reducing immunopathological- mediated lung damage while buying time for—and possibly aiding—viral clearance, and for reducing the morbidity and mortality of patients with COVID-19. This approach may also reduce the number of COVID-19 patients that require mechanical ventilation, supplemental oxygen, inpatient hospitalization, and Intensive Care Unit (ICU) level of care. Further, other viruses and bacterial infections can cause similar sequelae. Therefore, there is a need in the art generally for an immunomodulatory agent capable of reducing the hyperactive immune response related to such infections. SUMMARY [0007] The compositions and methods described herein are used to treat lung injury such as ARDS (e.g., the Berlin definition of ARDS). In some embodiments, the patient has ARDS caused by sepsis (viral or bacterial), including ARDS caused by COVID-19. In other embodiments, the patient is in stage II of COVID-19 characterized by severe pneumonia that persists, despite a decline in viral load, due to a hyperactive immune response including a cytokine storm and significant myeloid cell lung infiltration. In some embodiments, the patient exhibits clinical symptoms such as shortness of breath and hypoxia (PaO2/FiO2 ≤ 300 mmHg). In other embodiments, the patient has abnormal chest imaging, transaminitis, and/or low- normal procalcitonin. In other aspects, the treated human patient suffers from lung injury. In some embodiment, the lung injury patient is characterized by hypoxemia and shortness of breath, with a PaO2/FiO2 ≤ 300 mmHg. In some embodiments, the lung injury patient is requiring >4L supplemental oxygen to maintain >92% oxygen. [0008] Further, the treated patient may be in stage III of COVID-19 characterized by pulmonary destruction and/or multiple organ failure. The treated patient may have clinical symptoms such as ARDS, Systemic Inflammatory Response Syndrome (SIRS)/shock, and/or cardiac failure. In some embodiments, the patient exhibits elevated inflammatory markers such as CRP, LDH, IL-6, D-dimer, ferritin, troponin, and/or NT-proBNP elevation. [0009] More specifically, the treatment comprises parenterally administering (e.g., intravenously or subcutaneously) a therapeutically effective amount of an anti-GM-CSF antibody or antigen-binding fragment thereof to a human patient suffering from lung injury or ARDS secondary to infection. In one embodiment, the treatment employs a therapeutically effective loading dose followed by a therapeutically effective lower maintenance dose of an anti-GM-CSF antibody or an antigen-binding fragment thereof to the patient that results in reducing the severity of lung injury. In certain embodiments, the patient, when treated, is in phase II or III of COVID-19, and may be approaching the need for mechanical ventilation to remain alive. [00010] In another aspect, there is provided a method of lowering the incidence of morbidity and/or mortality of a human patient suffering from lung injury or ARDS secondary to sepsis, such as from COVID-19, comprising administering an effective amount of GM-CSF antagonist. In some embodiments, the GM-CSF antagonist is a monoclonal anti-GM-CSF antibody. In some embodiments, the monoclonal anti-GM-CSF antibody is gimsilumab os namilumab. For instance, such GM-CSF antagonist is gimsilumab or namilumab administered in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses. [00011] In other embodiments, the method comprises: (a) parenterally administering to the patient having ARDS an initial dose of about 50 mg to about 1000 mg of gimsilumab or namilumab; and (b) parenterally administering to the patient one or more subsequent doses of about 50 mg to about 1000 mg of gimsilumab or namilumab that results in reducing the severity of ARDS. Such patient may be in phase II or III of COVID-19. [00012] In another embodiment, a population of patients having lung injury or ARDS are treated with gimsilumab or namilumab administered in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses, wherein the treatment results in a statistically significant decrease in the incidence of mortality after treatment. In certain embodiments, the patients receive an initial dose of about 400 mg gimsilumab or namilumab on the first day of treatment (Day 1) followed by about 200 mg gimsilumab or namilumab seven days later (Day 8), wherein the treatment results in a statistically significant decrease in the incidence of mortality by Day 43 after treatment. In certain embodiments, there is a statistically significant decrease in mortality at Day 15 or Day 29 after treatment. In other embodiments, the second dose is omitted if a particular patient(s) is discharged from the hospital after the initial dose or no longer needs supplemental oxygen or ventilatory support. [00013] As further detailed below, for the therapies described herein, the incidence of mortality may be measured by the Cochran-Mantel-Haenszel (CMH) test controlled by country and/or the subjects’ baseline (classified as either lung injury/mild ARDS or moderate/severe ARDS). Mortality may also be measured by the Cox Proportional Model. [00014] As further detailed below, for the therapies described herein, the incidence of mortality may be measured by the logistical regression with the Treatment, country and subjects’ clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]). Mortality may also be measured by the Cox Proportional Model. [00015] Further, the efficacy of the therapies described herein may be measured by the percentage of subjects having each severity rating on a 7-point ordinal scale. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7. Death. In certain embodiments, the status on the 7-point ordinal scale is assessed daily while hospitalized, on the day of discharge (DoD), and on Days 15, 22, 29, 36, and 43 after treatment. Change in the ordinal scale at specific time points are summarized by proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point worsening). In other embodiments, the therapies disclosed herein result in a statistically significant number of patients who have a 1-, 2-, 3-, or 4-point improvement on the 7-point ordinal scale. [00016] In yet other embodiments, the efficacy of the therapies disclosed herein may be measured by one or more of the following: · Incidence and duration of mechanical ventilation use during the study. · Number of days in the ICU. · Number of days of inpatient hospitalization. · Incidence of mortality by Day 15, Day 29, Day 85, and Day 169 (End of Study (EoS)). · NEWS assessed daily while hospitalized. · Sequential Organ Failure Assessment (SOFA) score assessed daily while in the ICU. · The percentage of subjects reporting each severity rating on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone). · Status on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone). · Change from Baseline in SpO2/FiO2, assessed daily while hospitalized · Incidence and duration of oxygen use during the study. · Change from Baseline in viral load as measured by quantitative polymerase chain reaction (PCR) test on Days 2, 9, and day-of-discharge (DoD). · Change from Baseline in D-dimer, cardiac troponin I, lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP). · Serum gimsilumab or namilumab concentrations. [00017] In certain embodiments, the therapies disclosed herein result in a statistically significant number of patients who show improvement in one or more of these efficacy assessments. In other embodiments, the therapies disclosed herein, such as administering gimsilumab or namilumab in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses, result in one or more of the following: · A reduction in the time to an improvement of one category from baseline on the 7- point ordinal scale; · An improvement in the mean change from baseline in ranking on the 7-point ordinal scale; · A reduction in the time to hospital discharge (DoD); · A reduction in the time to achieve a National Early Warning Score (NEWS) to equal or less than 4 and maintained for 24 hours; and/or · A reduction in SARS-CoV-2 viral load. [00018] In one embodiment, the anti-GM-CSF antibody has variable heavy chain and variable light chain amino acid sequences set forth in SEQ ID NOs:1 and 2, respectively. Various embodiments described herein encompass using an anti-GM-CSF antibody having variable heavy and light chain amino acid sequences that are at least 90%, 95%, 98%, or at least 99% homologous with the amino sequence set forth in SEQ ID NOs:1 and 2, respectively, wherein the homologous anti-GM-CSF antibody(ies) retain the ability to bind GM-CSF and provide a benefit to the patient being treated for lung injury or ARDS from Covid-19. [00019] Further provided herein are pharmaceutical compositions comprising a GM-CSF antagonist and one or more pharmaceutically acceptable excipients. The GM-CSF antagonist comprises an antibody in various embodiments, including an antibody comprising a heavy chain variable domain comprising the CDR amino acid sequences set forth in SEQ ID NOs:3, 4, and 5; and a light chain variable domain comprising the CDR amino acid sequences set forth in SEQ ID NOs:6, 7, and 8. In various embodiments, the antibody comprises the heavy chain variable domain and the light chain variable domain amino acid sequences set forth in SEQ ID NOs:1 and 2, respectively. In various embodiments, the injectable pharmaceutical composition comprises one or more pharmaceutically acceptable excipients such as glutamate, polysorbate 80, and sorbitol. [00020] These and other embodiments of the compositions, methods, scales, and the like will be apparent from the following description, drawings, examples, and claims. BRIEF DESCRIPTION OF THE DRAWINGS [00021] The foregoing features of embodiments will be more readily understood by reference to the following detailed description, taken with reference to the accompanying drawings, in which: [00022] Figure 1 is simulated serum gimsilumab PK profile after gimsilumab 400 mg by intravenous infusion on the first day of treatment (Day 1) and gimsilumab 200 mg by intravenous infusion on Day 8. [00023] Figure 2 is a schematic of the study design. [00024] Figure 3 is an amino acid sequence for gimsilumab heavy chain (SEQ ID NO:1). The complementarity-determining regions (CDR) are underlined. [00025] Figure 4 is an amino acid sequence for gimsilumab light chain (SEQ ID NO:2). The complementarity-determining regions (CDR) are underlined. [00026] Figure 5 is an amino acid sequence for gimsilumab heavy chain CDR1 (SEQ ID NO:3). [00027] Figure 6 is an amino acid sequence for gimsilumab heavy chain CDR2 (SEQ ID NO:4). [00028] Figure 7 is an amino acid sequence for gimsilumab heavy chain CDR3 (SEQ ID NO:5). [00029] Figure 8 is an amino acid sequence for gimsilumab light chain CDR1 (SEQ ID NO:6). [00030] Figure 9 is an amino acid sequence for gimsilumab light chain CDR2 (SEQ ID NO:7). [00031] Figure 10 is an amino acid sequence for gimsilumab light chain CDR3 (SEQ ID NO:8). [00032] Figure 11 is an amino acid sequence for namilumab heavy chain variable region (SEQ ID NO:9). The complementarity-determining regions (CDRs) are underlined. [00033] Figure 12 is an amino acid sequence for namilumab light chain variable region (SEQ ID NO:10). The complementarity-determining regions (CDRs) are underlined. [00034] Figure 13 is an amino acid sequence for namilumab heavy chain CDR1 (SEQ ID NO:11). [00035] Figure 14 is an amino acid sequence for namilumab heavy chain CDR2 (SEQ ID NO:12). [00036] Figure 15 is an amino acid sequence for namilumab heavy chain CDR3 (SEQ ID NO:13). [00037] Figure 16 is an amino acid sequence for namilumab light chain CDR1 (SEQ ID NO:14). [00038] Figure 17 is an amino acid sequence for namilumab light chain CDR2 (SEQ ID NO:15). [00039] Figure 18 is an amino acid sequence for namilumab light chain CDR3 (SEQ ID NO:16). [00040] Figure 19 is an amino acid sequence for mature human GM-CSF (SEQ ID NO:17). [00041] Figure 20 illustrates three escalating phases of disease progression in COVID-19. Source: Siddiqi HK, Mehra MR. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. J Heart Lung Transplant. 2020. doi:10.1016/j.healun.2020.03.012. [00042] Figure 21 illustrates the patient flow through the study. [00043] Figure 22 shows Kaplan-Meier analysis of all-cause mortality. [00044] Figure 23 shows pre-specified subgroup analyses of (A) all-cause mortality at day 43, (B) ventilator-free survival at day 29, (C) time to hospital discharge. [00045] Figure 24 shows interim data (N=38) for levels of key biomarkers associated with COVID-19 progression (e.g., CRP and eGFR) in gimsilumab-treated patients relative to placebo-treated patients. DETAILED DESCRIPTION [00046] Various aspects and embodiments will be described herein. These aspects and embodiments may, however, be embodied in many different forms and should not be construed as limiting; rather, these embodiments are provided so the disclosure will be as thorough and complete so as to inform a person of skill how to make and use the compositions and methods described herein. The terminology used herein is for the purpose of describing the compositions and methods described herein, and is not intended to be limiting unless expressly stated, because the scope of the invention will be limited only by claims accompanying this application and claims accompanying continuation and divisional applications derived here from. All books, publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety. [00047] As can be appreciated from the foregoing and following description, each and every feature described herein, and each and every combination of two or more of such features, is included within the scope of the present disclosure provided that the features included in such a combination are not mutually inconsistent. For example, any embodiment whose use is consistent with any other embodiment is contemplated and thus included in this description. Other aspects and embodiments are set forth in the following description and claims, and also when considered in conjunction with the accompanying examples and drawings. [00048] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. For example, a reference to “a method” includes one or more methods, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure. A. DEFINITIONS [00049] Unless defined otherwise, all terms and phrases used herein include the meanings that the terms and phrases have attained in the art, unless the contrary is clearly indicated or clearly apparent from the context in which the term or phrase is used. Any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, including the particular methods and materials described herein. [00050] Unless otherwise stated, the use of individual numerical values are stated as approximations as though the values were preceded by the word “about” or “approximately.” Similarly, the numerical values in the various ranges specified in this application, unless expressly indicated otherwise, are stated as approximations as though the minimum and maximum values within the stated ranges were both preceded by the word “about” or “approximately.” In this manner, variations above and below the stated ranges can be used to achieve substantially the same results as values within the ranges. As used herein, the terms “about” and “approximately” when referring to a numerical value shall have their plain and ordinary meanings to a person of ordinary skill in the art to which the disclosed subject matter is most closely related or the art relevant to the range or element at issue. The amount of broadening from the strict numerical boundary depends upon factors known to those skilled in the art. For example, some of the factors which may be considered include the criticality of the element and/or the effect a given amount of variation will have on the performance of the claimed subject matter, as well as other considerations known to those of skill in the art. As used herein, the use of differing amounts of significant digits for different numerical values is not meant to limit how the use of the words “about” or “approximately” will serve to broaden or narrow a particular numerical value or range. As a general matter, “about” or “approximately” broaden the numerical value. The disclosure of ranges is intended as a continuous range including every value between the minimum and maximum values plus the broadening of the range afforded by the use of the term “about” or “approximately.” Consequently, recitation of ranges of values herein are intended to serve as a shorthand method of referring individually to each separate value falling within the range, and each separate value is incorporated into the specification as if it were individually recited herein. [00051] The terms “administer” or “administration” refer to the act of injecting or otherwise physically delivering a substance as it exists outside the body (e.g., a formulation of the invention) into a patient, such as by mucosal, intradermal, intravenous, subcutaneous, intramuscular delivery and/or any other method of physical delivery described herein or known in the art. When a disease or a symptom thereof is being treated, administration of the substance typically occurs after the onset of the disease or symptoms thereof. When a disease or symptoms thereof are being prevented, administration of the substance typically occurs before the onset of the disease or symptoms. [00052] “Adverse Events” or “AE” as used herein means any unfavorable or unintended change in body structure (signs), body function (symptoms), laboratory results (e.g., SpO2, chemistry, ECG, X-ray, etc.), or worsening of a preexisting condition associated temporally with the use of a therapeutic agent whether or not considered related to the agent. [00053] The term “antibody” is intended to refer to immunoglobulin molecules comprising four polypeptide chains, two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, as well as multimers thereof (e.g., IgM). Each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region comprises three domains, C _H1 , C _H2 , and CH3. Each light chain comprises a light chain variable region (abbreviated herein as LCVR or V _L ) and a light chain constant region. The light chain constant region comprises one domain (C _L1 ). The V _H and V _L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each V _H and V _L is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In different embodiments of the invention, the FRs of the anti-GM-CSF antibody (or antigen-binding portion thereof) may be identical to the human germline sequences, or may be naturally or artificially modified. An amino acid consensus sequence may be defined based on a side-by-side analysis of two or more CDRs. [00054] The term “antigen-binding protein” means a protein that binds to an antigen. For example, an antigen-binding protein includes, but is not limited to, an antibody, an antigen binding fragment of an antibody, a DVD-Ig, and a dual variable domain immunoglobulin. [00055] By the term “antagonist,” “blocker,” or “inhibitor,” means a substance that retards or prevents a chemical or physiological reaction or response. Common blockers or inhibitors include, but are not limited to, antisense molecules, antibodies, antagonists and their derivatives. [00056] The term “ARDS” refers to or describes the physiological condition in a mammal that is typically characterized by symptoms such as severe shortness of breath, labored and unusually rapid breathing, low blood pressure, confusion and extreme tiredness. Clinical classification criteria for ARDS are the Berlin definitions of ARDS shown in Table 1 below. Table 1. The Berlin Definition of Acute Respiratory Distress Syndrome Abbreviations: CPAP, continued positive airway pressure; FiO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure. aChest radiograph or computer tomography scan bIf altitude is higher than 100m, the correction factor should be calculated as follow: (PaO2/FiO2 x (barometric pressure/760)). cThis may be delivered noninvasively in the mild acute respiratory distress syndrome group. [00057] The terms “composition” and “formulation” are intended to encompass a product containing the specified ingredients (e.g., an anti-GM-CSF antibody) in, optionally, the specified amounts, as well as any product which results, directly or indirectly, from the combination of the specified ingredients in, optionally, the specified amounts. [00058] The term “coronavirus” refers to a family of zoonotic viruses that affect humans and cause respiratory tract infections such as common cold symptoms and more severe or even fatal conditions, e.g., severe pneumonia and ARDS. Examples of coronaviruses include alphacoronavirus, betacoronavirus, hCoV-229E, hCoV-NL63, hCoV-OC43, HCoV- HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. In some embodiments, the coronavirus is a betacoronavirus having a genome sequence of SARS-CoV-2. In other embodiments, the genome sequence of the coronavirus has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity with SARS-CoV-2. In another aspect, the genome sequence of the coronavirus has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity with a bat SARS-like CoV (bat-SL-CoVZC45, MG772933.1). The treatments described herein are useful in treating all such coronavirus infections and the symptoms arising thereof. [00059] The term “COVID-19” refers to a respiratory tract infection caused by a newly emergent conronavirus, SARS-CoV-2, that was first recognized in Wuhan, China in December 2019. Clinical syndromes of COVID-19 range from mild or uncomplicated illness such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore throat, dyspnea, nasal congestion, headache, or rarely, diarrhea, nausea, and vomiting to severe disease that requires hospitalization and oxygen support or the admission to an intensive care unit and may require mechanical ventilation. In severe cases, COVID-19 can be complicated by lung injury, ARDS, sepsis and septic shock, multi-organ failure, including acute kidney injury and cardiac injury. The most common diagnosis in severe COVID-19 patients is severe pneumonia. [00060] The term “epitope” refers to an antigenic determinant that interacts with a specific antigen binding site in the variable region of an antibody molecule known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas on an antigen and may have different biological effects. Epitopes may be either conformational or linear. A conformational epitope is produced by spatially juxtaposed amino acids from different segments of the linear polypeptide chain. A linear epitope is one produced by adjacent amino acid residues in a polypeptide chain. In certain circumstance, an epitope may include moieties of saccharides, phosphoryl groups, or sulfonyl groups on the antigen. [00061] The term “excipients” refers to inert substances that are commonly used as a diluent, vehicle, preservative, binder, stabilizing agent, etc. for drugs and includes, but is not limited to, proteins (e.g., serum albumin, etc.), amino acids (e.g., aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, leucine, etc.), fatty acids and phospholipids (e.g., alkyl sulfonates, caprylate, etc.), surfactants (e.g., SDS, polysorbate, nonionic surfactant, etc.), saccharides (e.g., sucrose, maltose, trehalose, etc.) and polyols (e.g., mannitol, sorbitol, etc.). See also Remington's Pharmaceutical Sciences, 21 ^st Ed., LWW Publisher (2005) for additional pharmaceutical excipients. [00062] In the context of a peptide or polypeptide, the term “fragment” refers to a peptide or polypeptide that comprises less than the full length amino acid sequence. Such a fragment may arise, for example, from a truncation at the amino terminus, a truncation at the carboxy terminus, and/or an internal deletion of a residue(s) from the amino acid sequence. Fragments may, for example, result from alternative RNA splicing or from in vivo protease activity. In various embodiments, anti-GM-CSF antibody fragments include polypeptides comprising an amino acid sequence of at least 50, at 100 amino acid residues, at least 125 contiguous amino acid residues, at least 150 contiguous amino acid residues, at least 175 contiguous amino acid residues, at least 200 contiguous amino acid residues, or at least 250 contiguous amino acid residues of the amino acid sequence of an anti-GM-CSF antibody heavy chain or light chain polypeptide. In various embodiments, a fragment of an antibody that specifically binds to a GM-CSF antigen retains at least 1, at least 2, or at least 3 functions of the full-length antibody. [00063] The term “GM-CSF antagonist” refers to a GM-CSF antigen or receptor- based antagonist including, for example, an anti-GM-CSF antibody or anti-GM-CSF binding fragment thereof. For a description of GM-CSF-receptor based antagonists including anti-GM- CSF antibodies such as gimsilumab or namilumab, see U.S. Pat. Nos. 10,023,632; 8,017,748; and US 9,067,993. As used herein, a “GM-CSF antagonist” is any agent which binds to or interacts with human GM-CSF or its receptor and inhibits the normal biological function of GM-CSF in vitro or in vivo. [00064] The term “GM-CSF antigen” refers to a GM-CSF polypeptide to which an antibody specifically binds. A GM-CSF antigen also refers to an analog or derivative of a GM- CSF polypeptide or fragment thereof to which an antibody specifically binds. A region of a GM-CSF polypeptide contributing to an epitope may be contiguous amino acids of the polypeptide, or the epitope may come together from two or more non-contiguous regions of the polypeptide. The epitope may or may not be a three-dimensional surface feature of the antigen. A localized region on the surface of a GM-CSF antigen that is capable of eliciting an immune response (e.g., specific bindings of an antibody) is a GM-CSF epitope. The epitope may or may not be a three-dimensional surface feature of the antigen. [00065] An “isolated antibody” means an antibody that has been identified and separated and/or recovered from at least one component of its natural environment. For example, an antibody that has been separated or removed from at least one component of an organism, or from a tissue or cell in which the antibody naturally exists or is naturally produced, is an “isolated antibody” for purposes of the present invention. An isolated antibody also includes an antibody in situ within a recombinant cell. Isolated antibodies are antibodies that have been subjected to at least one purification or isolation step. According to certain embodiments, an isolated antibody may be substantially free of other cellular material and/or chemicals. [00066] The term “human granulocyte macrophage-colony stimulating factor” or “human GM-CSF” or “hGM-CSF” refers to GM-CSF having the amino acid sequence of SEQ ID NO:9, or a biologically active fragment thereof. [00067] The term “intravenous infusion” refers to introduction of a drug into the vein of an animal or human patient over a period of time greater than approximately 5 minutes, in various embodiments between approximately 30 to 90 minutes, although intravenous infusion may be alternatively administered for 10 hours or longer, for instance, continuous infusion over several days, e.g., 1 to 30 days. [00068] The term “K _D ” is intended to refer to the equilibrium dissociation constant of a particular antibody-antigen interaction. A variety of analytical methods have been established to determine the K _D values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal titration calorimetry. [00069] The term “loading dose” or “front loading” when referring to drug administration, describes an initially higher dose followed by the same or lower dose(s) at one or more intervals. The initial higher dose or doses are meant to more rapidly increase the animal or human patient’s serum drug concentration to an efficacious target serum concentration. In various embodiments, front loading is achieved by an initial dose or doses delivered over three weeks or less that causes the animal’s or patient’s serum concentration to reach a target serum trough concentration. The initial front-loading dose or series of doses is administered in 1 week or less, including 1 day or less. In some cases, where the initial dose is a single dose and is not followed by a subsequent maintenance dose for at least 1 week, the initial dose is administered in 1 day or less. Where the initial dose is a series of doses, in various embodiments each dose is separated by at least 3 hours, but not more than 3 weeks or less, or 2 weeks or less, or 1 week or less, or 1 day or less. [00070] The term “lung injury” refers to or describes the physiological condition in mammals that is typically characterized by hypoxemia and shortness of breath, with a PaO2/FiO ₂ ≤ 300 mmHg. Lung injury can also refer to the state of requiring >4L supplemental oxygen to maintain >92% oxygen. Lung injury can be caused by a viral infection, such as by SARS-CoV-2. [00071] “National Early Warning Score (NEWS)” as used herein is a score that has demonstrated an ability to discriminate patients at risk of poor outcomes (WHO Master Protocol, 2020). This score is based on 7 clinical parameters (Table 2). The NEWS is used as an efficacy measure. Table 2. National Early Warning Score Level of consciousness = alert (A), and arousable only to voice (V) or pain (P), and unresponsive (U). [00072] The term “optional” or “optionally” means that the subsequently described element, component or circumstance may or may not occur, so that the description includes instances where the element, component, or circumstance occurs and instances where it does not. [00073] The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. [00074] The terms “patient” and “subject” are used interchangeably. As used herein, a subject is a human having a GM-CSF-mediated disease or condition (e.g., an immunopathological state). In various embodiments, the subject is a human at risk of developing a GM-CSF-mediated disease or condition. In various embodiments, the subject is a human with confirmed or suspected COVID-19. In various embodiments, the subject is a human with pathophysiological symptoms of COVID-19 such as, for example and not by limitation, a human with COVID-19 suffering from an immunopathological condition, e.g., a cytokine storm. [00075] The term “peak serum concentration” refers to the maximal serum drug concentration shortly after delivery of the drug into the animal or human patient, after the drug has been distributed throughout major circulatory vessels, but before significant tissue distribution, metabolism, or excretion of drug by the body has occurred. [00076] The term “serum concentration,” “serum drug concentration,” or “serum anti-GM-CSF antibody concentration” refers to the concentration of a drug, such as an anti- GM-CSF antibody, in the blood serum or plasma of an animal or human patient being treated with the drug. Serum concentration may be determined by immunoassay. In one embodiment, the immunoassay is an ELISA. Any method suitable for determining serum concentration of an anti-GM-CSF antibody or antigen-binding fragment thereof would be suitable for use herein. [00077] The term “Seven (7)-point ordinal scale” as used herein is a scale used to assess the clinical status at the first assessment of a given study day as described in the WHO COVID-19 Master Protocol, 2020. The scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death. [00078] The term “specifically binds” or the like, means that an antibody or antigen- binding fragment thereof forms a complex with an antigen that is relatively stable under physiologic conditions. Methods for determining whether an antibody specifically binds to an antigen are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. For example, an antibody that “specifically binds” GM-CSF, as used in the context of the present invention, includes antibodies that bind GM-CSF or portion thereof with a KD of less than about 1000 nM, less than about 500 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM or less than about 0.5 nM, as measured in a surface plasmon resonance assay. An isolated antibody that specifically binds human GM-CSF, however, have cross-reactivity to other antigens, such as GM-CSF molecules from other (non-human) species. [00079] “Statistically significant” as used herein means statistical data having a “P” value generally of less than 0.05. In context of the present disclosure, clinical trials are generally designed to test the superiority of an intervention (e.g., in this case, a treatment) as compared with a control. Given that clinical trials involve people, each of whom are physiologically different from one another, variations in the results naturally occur. Statistics are therefore used to determine whether any observed differences are caused by chance or by the intervention itself. Measures of statistical significance quantify the probability of a study’s result being due to chance. The “P” value, frequently used to measure statistical significance, is the probability that the study results are due to chance rather than to a real treatment effect. Generally, the conventional cutoff for the “P” value to be considered statistically significant is 0.05, or 5% although it may change depending on study design and outcomes. If the “P” value is less than 0.05, this means that the possibility of the results in the study being due to chance is less than 5%. If the “P” value is greater than 0.05 (5%), any difference between the treated group and control group is not statistically significant—meaning that the difference cannot confidently be attributed to the treatment, but instead may be due to chance. [00080] The term “subcutaneous administration” refers to introduction of a drug under the skin of an animal or human patient, generally within a pocket between the skin and underlying tissue, by relatively slow, sustained delivery from a drug receptacle. The pocket may be created by pinching or drawing the skin up and away from underlying tissue. [00081] The term “surface plasmon resonance” refers to an optical phenomenon that allows for the analysis of real-time interactions by detection of alterations in protein concentrations within a biosensor matrix, for example using the BIAcore™ system (Biacore Life Sciences division of GE Healthcare, Piscataway, N.J.). [00082] The term “therapeutic agent” refers to any agent that can be used in the treatment, management, or amelioration of a GM-CSF-mediated disease or condition and/or a symptom related thereto. In certain embodiments, the term “therapeutic agent” refers to an anti-GM-CSF antibody. In various embodiments, the anti-GM-CSF antibody is gimsilumab. In various embodiments, the anti-GM-CSF antibody is namilumab. [00083] The term “therapy” refers to any protocol, method, and/or agent that can be used in the prevention, management, treatment, and/or amelioration of a GM-CSF-mediated disease or condition (e.g., lung injury or ARDS). In various embodiments, the terms “therapies” and “therapy” refer to a biological therapy, supportive therapy, and/or other therapies useful in the prevention, management, treatment, and/or amelioration of a GM-CSF- mediated disease or condition known to those of skill in the art, such as medical personnel. [00084] The term “therapeutically effective dose” or “therapeutically effective amount,” refers to a dose or amount that produces the desired effect for which it is administered. See, e.g., Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999)). Efficacy can be measured in conventional ways, depending on the disease or condition to be treated. For example, efficacy can be measured comparing the mortality for a predetermined period for human patients treated with and without the GM-CSF antagonists provided herein. For lung injury or ARDS, efficacy can also be measured by a 7-point ordinal scale. Therapeutically effective amount also refers to a target serum concentration, such as a trough serum concentration, that has been shown to be effective in suppressing disease symptoms when maintained for a period of time. [00085] The terms “treat,” “treatment,” and “treating” refer to the reduction or amelioration of the progression, severity, and/or duration of a GM-CSF-mediated disease or condition (e.g., lung injury or ARDS) resulting from the administration of one or more therapies (including, but not limited to, the administration of one or more prophylactic or therapeutic agents). In various embodiments, such terms refer to the reduction or inhibition of the GM-CSF pathway. [00086] The term “trough serum concentration” refers to the serum drug concentration at a time after delivery of a previous dose and immediately prior to delivery of the next subsequent dose of drug in a series of doses. In certain cases, the trough serum concentration is a minimum sustained efficacious drug concentration in a series of drug administrations. Also, the trough serum concentration is frequently targeted as a minimum serum concentration for efficacy because it represents the serum concentration at which another dose of drug is to be administered as part of a treatment regimen. In one embodiment, when a therapeutically effective amount of gimsilumab is administered (one or more times), the trough serum concentration of at least about 20 mcg/mL is maintained for at least 2 weeks. In other embodiments, such trough serum concentration is at least about 25 mcg/mL, or at least about 30 mcg/mL, or at least about 35 mcg/mL, or at least about 40 mcg/mL, or at least about 50 mcg/mL, or at least about 60 mcg/mL. In another embodiment, when a therapeutically effective amount of gimsilumab is administered (one or more times), the trough serum concentration is below about 20 mcg/mL and is maintained for at least 2 weeks. In other embodiments, such trough serum concentration is at least about 17.5 mcg/mL, or at least about 15 mcg/mL, or at least about 12.5 mcg/mL, or at least about 10 mcg/mL, or at least about 7.5 mcg/mL, or at least about 5 mcg/mL. B. GM-CSF ANTAGONISTS USEFUL TO TREAT GM-CSF-MEDIATED DISEASE [00087] A number of therapeutic agents are useful in the treatment, management, or amelioration of a GM-CSF-mediated disease or condition and/or a symptom related thereto. As described below, these agents include antigen binding proteins that specifically bind GM- CSF. Non-limiting examples of categories of such proteins that act as GM-CSF antagonists include small molecule GM-CSF antagonists, peptide-based GM-CSF antagonists (e.g., “peptibody” molecules), and antibodies or antigen-binding fragments of antibodies that specifically bind human GM-CSF. The antibodies may be human, mouse (or other animal), or recombinant antibodies. [00088] In one embodiment, the anti-GM-CSF antibody, gimsilumab (KIN-1901), is effective in treating patients with lung injury or ARDS secondary to sepsis, including from COVID-19. As detailed in Example 1 below, gimsilumab administered intravenously or subcutaneously was shown to be well-tolerated in phase 1 clinical trials in healthy volunteers or rheumatoid arthritis patients. Gimsilumab has been previously described in U.S. Pat. No. 10,023,632 (SEQ ID NOs: 8 and 12). [00089] In other embodiments, the anti-GM-CSF antibody, or antigen-binding fragment thereof, that can be used in the methods of the present invention has HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 amino acid sequences selected from SEQ ID NOs: 3/4/5/6/7/8. See U.S. Pat. No.10,023,632 (SEQ ID NOs: 40/41/42/43/44/45). [00090] The antibody may comprise the heavy chain variable domain and the light chain variable domain amino acid sequences set forth in SEQ ID NOs:1 and 2, respectively. In further embodiments, the antibody or antigen-binding fragment thereof comprises HC/LC amino acid sequence pairs selected from the group consisting of SEQ ID NOs: 1 and 2. [00091] In one embodiment, the anti-GM-CSF antibody namilumab is administered intravenously or subcutaneously. Namilumab has been previously described in U.S. Pat. No. 8,017,748 and U.S. Pat. No.9,067,993 (SEQ ID NOs:19 and 21). [00092] In various embodiments, the anti-GM-CSF antibody or antigen-binding fragment thereof that can be used in the methods of the present invention has HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 amino acid sequences selected from SEQ ID NOs: 11/12/13/14/15/16. See U.S. Pat. No.9,067,993 (SEQ ID NOs: 14/15/2/16/17/18). [00093] The antibody may comprise the heavy chain variable domain and the light chain variable domain amino acid sequence set forth in SEQ ID NOs:9 and 10. [00094] In various embodiments, the anti-GM-CSF antibody or antigen-binding fragment thereof specifically binds to an epitope of human GM-CSF comprising amino acids 23-27 (RRLLN) of SEQ ID NO:17 and/or amino acids 65-77 (GLRGSLTKLKGPL) of SEQ ID NO:17. [00095] The GM-CSF antagonist may be an antibody comprising a heavy chain variable domain comprising the CDR amino acid sequences set forth in SEQ ID NOs: 3, 4, and 5 or SEQ ID NOs:11, 12, and 13; and a light chain variable domain comprising the CDR amino acid sequences set forth in SEQ ID NOs: 6, 7, and 8 or SEQ ID NOs:14, 15, and 16. The anti- GM-CSF antibodies (or GM-CSF-binding fragments thereof) useful as therapeutic agents for treating lung injury or ARDS may comprise one or more amino acid substitutions, insertions and/or deletions in the framework and/or CDR regions of the heavy and light chain variable domains as compared to the corresponding germline sequences from which the antibodies were derived. Such mutations can be ascertained by comparing the amino acid sequences disclosed herein to germline sequences available from, for example, public antibody sequence databases. The present invention includes methods involving the use of antibodies, and antigen-binding fragments thereof, which are derived from any of the amino acid sequences disclosed herein, wherein one or more amino acids within one or more framework and/or CDR regions are mutated to the corresponding residue(s) of the germline sequence from which the antibody was derived, or to the corresponding residue(s) of another human germline sequence, or to a conservative amino acid substitution of the corresponding germline residue(s) (such sequence changes are referred to herein collectively as “germline mutations”). A person of ordinary skill in the art, starting with the heavy and light chain variable region sequences disclosed herein, can produce antibodies and antigen-binding fragments which comprise one or more individual germline mutations or combinations thereof. In certain embodiments, all of the framework and/or CDR residues within the V _H and/or V _L domains are mutated back to the residues found in the original germline sequence from which the antibody was derived. In other embodiments, only certain residues are mutated back to the original germline sequence, e.g., only the mutated residues found within the first 8 amino acids of FR1 or within the last 8 amino acids of FR4, or only the mutated residues found within CDR1, CDR2 or CDR3. In other embodiments, one or more of the framework and/or CDR residue(s) are mutated to the corresponding residue(s) of a different germline sequence (i.e., a germline sequence that is different from the germline sequence from which the antibody was originally derived). [00096] Furthermore, the antibodies used as therapeutic agents herein may contain any combination of two or more germline mutations within the framework and/or CDR regions, e.g., wherein certain individual residues are mutated to the corresponding residue of a particular germline sequence while certain other residues that differ from the original germline sequence are maintained or are mutated to the corresponding residue of a different germline sequence. Once obtained, antibodies and antigen-binding fragments that contain one or more germline mutations can be tested for one or more desired property such as, improved binding specificity, increased binding affinity, improved or enhanced antagonistic or agonistic biological properties (as the case may be), reduced immunogenicity, etc. The use of antibodies and antigen-binding fragments obtained in this general manner are encompassed within the present invention. [00097] The present disclosure also includes the use of anti-GM-CSF antibodies (or GM-CSF-binding fragments thereof) comprising variants of any of the HCVR, LCVR, and/or CDR amino acid sequences disclosed herein having one or more conservative substitutions. For example, the use of anti-GM-CSF antibodies having HCVR, LCVR, and/or CDR amino acid sequences with, e.g., 20 or fewer, 15 or fewer, 10 or fewer, 8 or fewer, 7 or fewer, 6 or fewer etc. conservative amino acid substitutions relative to any of the HCVR, LCVR, and/or CDR amino acid sequences disclosed herein. [00098] Specific examples of human antibodies or antigen-binding fragments of antibodies that specifically bind GM-CSF which can be used as therapeutic agents include any antibody or antigen-binding fragment which comprises the three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) having an amino acid sequence within SEQ ID NO:1 or SEQ ID NO:9, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. The antibody or antigen-binding fragment may comprise the three light chain CDRs (LCVR1, LCVR2, LCVR3) contained within a light chain variable region (LCVR) having an amino acid sequence within SEQ ID NO:2 or SEQ ID NO:10, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98% or at least 99% sequence identity. For example, the present disclosure encompasses antibodies having at least 80%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity with gimsilumab or namilumab. [00099] In other aspects, the antibody or antigen-binding fragment thereof comprises the six CDRs (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3) from the heavy and light chain amino acid sequence pair (HC/LC) of SEQ ID NOs:1/2 or heavy and light chain variable region sequence pair (HCVR/LCVR) of SEQ ID NOs:9/10. [000100] In various embodiments, anti-GM-CSF antibody fragments include polypeptides comprising an amino acid sequence of at least 50 amino acid residues, at 100 amino acid residues, at least 125 contiguous amino acid residues, at least 150 contiguous amino acid residues, at least 175 contiguous amino acid residues, at least 200 contiguous amino acid residues, or at least 250 contiguous amino acid residues of the amino acid sequence of an anti- GM-CSF antibody heavy chain or light chain polypeptide. In various embodiments, a fragment of an antibody that specifically binds to a GM-CSF antigen retains at least 1, at least 2, or at least 3 functions of the full-length antibody. [000101] Non-limiting examples of antigen binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3- CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g. monovalent nanobodies, bivalent nanobodies, etc.), small modular immunopharmaceuticals (SMIPs), and shark variable IgNAR domains, are also encompassed within the expression “antigen binding fragment.” [000102] An antigen binding fragment of an antibody will typically comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VH domain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH-VH, VH-VL or VL-VL dimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH or VL domain. [000103] In certain embodiments, an antigen binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non- limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody of the present invention include: (i) VH-CH1; (ii) VH-CH2; (iii) VH-CH3; (iv) VH-CH1-CH2; (v) VH-CH1-CH2-CH3; (vi) VH-CH2-CH3; (vii) VH-CL; (viii) V _L -C _H1 ; (ix) V _L -C _H2 ; (x) V _L -C _H3 ; (xi) V _L -C _H1 -C _H2 ; (xii) V _L -C _H1 -C _H2 -C _H3 ; (xiii) V _L -C _H2 - C _H3 ; and (xiv) V _L -C _L . In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60 or more) amino acids which result in a flexible or semi-flexible linkage between adjacent variable and/or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody of the present invention may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non-covalent association with one another and/or with one or more monomeric V _H or V _L domain (e.g., by disulfide bond(s)). [000104] As with full antibody molecules, antigen-binding fragments may be monospecific or multispecific (e.g., bispecific). A multispecific antigen-binding fragment of an antibody will typically comprise at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen. Any multispecific antibody format, including the exemplary bispecific antibody formats disclosed herein, may be adapted for use in the context of an antigen-binding fragment of an antibody of the present invention using routine techniques available in the art. [000105] The constant region of an antibody is important in the ability of an antibody to fix complement and mediate cell-dependent cytotoxicity. Thus, the isotype of an antibody may be selected on the basis of whether it is desirable for the antibody to mediate cytotoxicity. C. PHARMACEUTICAL COMPOSITIONS USEFUL TO TREAT GM-CSF- MEDIATED DISEASE [000106] The antigen binding proteins described herein may be formulated into pharmaceutical compositions suitable for administration to human patients, e.g., patients suffering from lung injury or ARDS, wherein a GM-CSF antagonist is contained within a pharmaceutical composition. Pharmaceutical compositions of the present disclosure are formulated with suitable carriers, excipients, and other agents that provide suitable transfer, delivery, tolerance, and the like. See, e.g., Remington's Pharmaceutical Sciences, 21 ^st Ed., LWW Publisher (2005). [000107] Injectable preparations may include dosage forms (e.g., vials, ampoules, bags) for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, and the like. For example, injectable preparations may be prepared, e.g., by dissolving or suspending or the antigen binding protein or its salt in a sterile aqueous medium suitable for injections, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent. In various embodiments, the injection thus prepared is filled in an ampoule or vial, and packaged with a package insert. In various embodiments, the pharmaceutically acceptable excipients are glutamate, polysorbate 80, sorbitol, and water or normal saline. [000108] In one embodiment, the pharmaceutical composition comprises about gimsilumab 100 mg/mL, 20 mM glutamate, 200 mM sorbitol, 0.05% (w/w) polysorbate 80, and water or normal saline in a 1.2 mL vial wherein the solution is at pH 5.0. For example, for a dose of 400 mg gimsilumab, 4 mL of such solution is withdrawn from the vial and diluted in 100 mL 0.9% normal saline for injection. For a dose of 200 mg gimsilumab, 2 mL of such solution is withdrawn from the vail and diluted in 100 mL 0.9% normal saline for injection. [000109] In another embodiment, the pharmaceutical composition comprises about gimsilumab 5 mg/mL, 10 mM sodium phosphate, 150 mM sodium chloride, 0.01% (w/w) polysorbate 80, and water wherein the solution is at pH 7.2. [000110] In certain embodiments, the approximate concentrations of ingredients that may be present in the pharmaceutical composition are as follows: · Gimsilumab: 1 mg/mL to 200 mg/mL · Glutamate: 1 mM to 100 mM · Sodium phosphate: 1 mM to 30 mM · Sodium chloride: 10 mM to 300 mM · Sorbitol: 10 mM to 300 mM · Polysorbate 80: 0.01% to 2% [000111] In various embodiments, the pharmaceutical composition is a stable liquid formulation comprising at least about 100 mg/ml and less than about 200 mg/ml namilumab; a tonicity modifier selected from mannitol, sorbitol, sucrose and/or trehalose, wherein the tonicity modifier is present in a concentration from about 3% to about 7% (w/v); and a buffer selected from a histidine, acetate and/or citrate buffer, wherein the buffer is present in a concentration from about 10 mM to about 50 mM, and wherein the pH is between about 5 and about 7. [000112] In various embodiments, the pharmaceutical composition comprises at least about 50 mg/ml namilumab; a tonicity modifier selected from mannitol, sorbitol, sucrose and/or trehalose, wherein the tonicity modifier is present in a concentration from about 1% to about 15% (w/v); and a buffer selected from a histidine, acetate and/or citrate buffer, wherein the buffer is present in a concentration from about 10 mM to about 50 mM, and wherein the pH is between about 5 and about 7, and wherein the composition is stable. [000113] Other excipients that may be utilized in the gimsilumab or namilumab compositions include aspartate, arginine, lysine, proline, glycine, histidine, methionine, mannitol, xylitol, Poloxamer 188, sodium dodecyl sulfate, lecithin, sodium glycolate, and polyoxyethylated castor oil. [000114] The pH of the composition may range from about 4 to 6, or about 5 to 8, or about 6 to 7, or about 4.8 to 5.2, or about 6.8 to 7.2. [000115] The pharmaceutical compositions described herein may be administered by a variety of methods, typically by injection, such as intravenous, subcutaneous, intradermal, and intramuscular routes. D. METHODS OF TREATING GM-CSF-MEDIATED DISEASE [000116] The antigen binding proteins and related pharmaceutical compositions described herein are useful for treating GM-CSF-mediated disease such as lung injury or ARDS (e.g., the Berlin definition of ARDS). In some embodiments, the patient has ARDS caused by sepsis, including ARDS caused by COVID-19. In other embodiments, the patient is in stage II of COVID-19 characterized by severe pneumonia that persists, despite a decline in viral load, due to a hyperactive immune response including a cytokine storm and significant myeloid cell lung infiltration. In some embodiments, the patient exhibits clinical symptoms such as shortness of breath and hypoxia (PaO2/FiO2 ≤ 300 mmHg). In other instances, the patient has abnormal chest imaging, transaminitis, and/or low-normal procalcitonin. Alternatively, the treated human patient has a PaO ₂ /FiO ₂ equal to or less than 300 mmHg, without invasive or non-invasive ventilation or with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) less than 5 cm H ₂ O. [000117] Further, the patient may be in stage III of COVID-19 characterized by pulmonary destruction and/or multiple organ failure. The patient may have clinical symptoms such as ARDS, SARS/shock, and/or cardiac failure. In some embodiments, the patient exhibits elevated inflammatory markers such as CRP, LDH, IL-6, D-dimer, ferritin, troponin, and/or NT-proBNP elevation. [000118] In one aspect, the treatment comprises parenterally administering (e.g., intravenously or subcutaneously) a therapeutically effective amount of an anti-GM-CSF antibody or antigen-binding fragment thereof to a human patient suffering from lung injury or ARDS secondary to sepsis. In another embodiment, the treatment employs a therapeutically effective loading dose followed by a therapeutically effective lower maintenance dose of an anti-GM-CSF antibody or an antigen-binding fragment thereof to the patient that results in reducing the severity of ARDS. In certain embodiments, the patient, when treated, is in phase II or III of COVID-19 and may be approaching the need for mechanical ventilation to remain alive. [000119] In another aspect, there is provided a method of lowering the incidence of morbidity and/or mortality of a human patient suffering from lung injury or ARDS secondary to sepsis, such as from COVID-19, comprising administering an effective amount of GM-CSF antagonist. For instance, such GM-CSF antagonist is gimsilumab or namilumab administered in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses. Such infusion may be over 1 hour. [000120] In other embodiments, the method comprises: (a) parenterally administering to the patient having ARDS an initial dose of about 50 mg to about 1000 mg of gimsilumab or namilumab; and (b) parenterally administering to the patient one or more subsequent doses of about 50 mg to about 1000 mg of gimsilumab or namilumab that results in reducing the severity of ARDS. Such patient may be in phase II or III of COVID-19. [000121] In another embodiment, a population of patients having lung injury or ARDS are treated with gimsilumab or namilumab administered in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses, wherein the treatment results in a statistically significant decrease in the incidence of mortality after treatment. In certain embodiments, the patients receive an initial dose of about 400 mg gimsilumab on the first day of treatment (Day 1) followed by about 200 mg gimsilumab seven days later (Day 8), wherein the treatment results in a statistically significant decrease in the incidence of mortality by Day 43 after treatment. In certain embodiments, there is a statistically significant decrease in mortality at Day 15 or Day 29 after treatment. In other embodiments, the second dose is omitted if a particular patient(s) is discharged from the hospital after the initial dose or no longer needs supplemental oxygen or ventilatory support. [000122] In other embodiments, the therapies disclosed herein, such as administering gimsilumab or namilumab in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses, result in one or more of the following: · A reduction in the time to an improvement of one category from baseline on the 7- point ordinal scale; · An improvement in the mean change from baseline in ranking on the 7-point ordinal scale; · A reduction in the time to hospital discharge (DoD); · A reduction in the time to achieve a National Early Warning Score (NEWS) to equal or less than 4 and maintained for 24 hours; and/or · A reduction in SARS-CoV-2 viral load. [000123] In one embodiment, the dosing regimens described herein allow attainment of an efficacious target trough serum concentration of the GM-CSF antagonist by providing an initial dose or doses of GM-CSF antagonist followed by subsequent doses of equal or smaller amounts of GM-CSF antagonist (i.e., greater front loading). The efficacious target trough serum concentration may be reached in 2 weeks or less, or 1 week or less, including 1 day or less. The target serum concentration may thereafter be maintained for 4 weeks or less, or 3 weeks or less, or 2 weeks or less, or 1 week or less by the administration of maintenance doses of equal or smaller amounts for the remainder of the treatment regimen or until clinically acceptable suppression of disease symptoms is achieved. In one aspect, the target trough serum concentration for gimsilumab is about 20 mcg/mL. [000124] In another embodiment, the patient is administered gimsilumab or namilumab by continuous IV infusion over a period of about 1 to 30 days wherein the serum concentration is maintained at about 1 mcg/mL to about 80 mcg/mL throughout such period. In other aspects, the period is about 5 days, or 10 days, or 15 days, or 20 days, or 25 days, and the serum concentration is maintained at about 10 mcg/mL to about 50 mcg/mL, or about 10 mcg/mL to about 30 mcg/mL, or about 15 mcg/mL to 25 mcg/mL, or about 18 mcg/mL to about 22 mcg/mL, or about 20 mcg/mL. [000125] The amount of GM-CSF antagonist (e.g., anti-GM-CSF antibody, GM- CSF-binding fragment thereof, etc.) administered to a subject according to the methods and compositions described herein is, generally, a therapeutically effective amount. The administration of a therapeutically effective amount of GM-CSF antagonist results in a lower incidence of mortality and/or morbidity and/or an improvement in one or more criteria of the 7-point ordinal score as compared to without any treatment. [000126] The amount of anti-GM-CSF antibody contained within the individual doses may be expressed in terms of milligrams of antibody per kilogram of patient body weight (i.e., mg/kg). For example, the anti-GM-CSF antibody may be administered to a patient at a dose of about 0.0001 to about 10 mg/kg of patient body weight. [000127] The amount of anti-GM-CSF antibody contained within the individual doses may be in milligrams with no body weight adjustment, i.e., a “flat dose.” For example, the anti-GM-CSF antibody, such as gimsilumab, may be administered to a patient at a dose of about 400 mg regardless of a patient’s body weight. In various embodiments, both the initial dose and the subsequent dose(s) of anti-GM-CSF antibody are administered doses without adjustment to the patient’s body weight. [000128] In one embodiment, injectable pharmaceutical compositions comprising gimsilumab are administered to a subject at an initial dose of about 400 mg on Day 1 of treatment and a subsequent dose of 200 mg on Day 8. In various embodiments, the initial dose on Day 1 is about 50 mg to about 1000 mg, or about 100 mg to 900 mg, or about 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 500 mg. The subsequent dose on Day 8 may be about 50 mg to about 1000 mg, or about 100 mg to 900 mg, or about 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 500 mg. [000129] In one embodiment, injectable pharmaceutical compositions comprising namilumab are administered to a subject at a single dose of about 150 mg on Day 1. In other embodiments the single dose on Day 1 is about 300 mg. In other embodiments, the single dose on Day 1 is about 50 mg to about 1000 mg, or about 100 mg to 900 mg, or about 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 500 mg. [000130] In various embodiments, the initial dose of an anti-GM-CSF antibody, such as gimsilumab or namilumab, or an antigen-binding fragment of gimsilumab or namilumab, is in the range of approximately 0.0085 mg to 10 mg per kg body weight (mg/kg), or 0.36 mg/kg to 10 mg/kg, or 0.3 mg to 30 mg/kg. In various embodiments, the initial dose is in the range of approximately 0.5 mg/kg to 10 mg/kg. In various embodiments, the initial dose is in the range of approximately 1 mg/kg to 6 mg/kg. In various embodiments, the cumulative weekly dose is in the range of 0.3 to 30 mg/kg. [000131] In various embodiments, at least one subsequent dose of an anti-GM-CSF antibody, such as gimsilumab or namilumab, or antigen-binding fragment thereof is in the range of approximately between 0.3 mg/kg body weight to 30 mg/kg. In various embodiments, at least one subsequent dose is in the range of approximately 0.5 mg/kg to 10 mg/kg. In various embodiments, at least one subsequent dose is in the range of approximately 1 mg/kg to 6 mg/kg. [000132] In various embodiments, an anti-GM-CSF antibody, such as gimsilumab or namilumab, may be administered as to a patient without adjustment to a patient’s body weight. Exemplary therapeutically effective amounts of antibody can be from about 75 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, or about 600 mg, or about 650 mg, or about 700 mg, or about 750 mg, or about 800 mg, or about 850 mg, or about 900 mg, or about 950 mg, or about 1000 mg of the anti-GM- CSF antibody. [000133] In various embodiments, subsequent doses are separated in time from each other by at least 1 day, at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, or at least 3 months. The dosing cycle may be repeated as desired to achieve clinically acceptable suppression of disease symptoms. [000134] In various embodiments, the anti-GM-CSF antibody is administered to a subject intravenously, e.g., via intravenous infusion over a period of 30 to 90 minutes, or in some cases over 60 minutes. [000135] Desirable serum concentrations for gimsilumab or namilumab range from about 1 mcg/mL to about 300 mcg/mL, for example, about 5 mcg/mL, about 10 mcg/mL, about 20 mcg/mL, about 30 mcg/mL, about 40 mcg/mL, about 50 mcg/mL, about 60 mcg/mL, about 70 mcg/mL, or about 80 mcg/mL. In one embodiment, when therapeutically effective amounts of gimsilumab are administered, the trough serum concentration of at least 15 mcg/mL is maintained for at least 2 weeks, or at least 20 mcg/mL is maintained for at least 2 weeks. In another aspect, when therapeutically effective amounts of gimsilumab are administered to a population of patients, at least 50% of the patients have serum concentrations of at least 15 mcg/mL for at least two weeks. For instance, when gimsilumab 400 mg is administered as a loading dose on Day 1 followed by gimsilumab 200 mg on Day 8, at least 50% of the patients have serum concentrations of at least 15 mcg/mL for at least two weeks, or at least 75% of the patients have serum concentrations of at least 20 mcg/mL for at least two weeks, or at least 90% of the patients have serum concentrations of at least 20 mcg/mL for at least two weeks. In other embodiments, the serum concentrations above are maintained for at least 3 weeks, or at least 4 weeks. [000136] In another embodiment, a population of patients having lung injury or ARDS are treated with gimsilumab or namilumab administered in an amount of about 50 mg to about 1000 mg by intravenous infusion in one or more doses, wherein the treatment results in a statistically significant decrease in the incidence of mortality after treatment. In certain embodiments, the patients receive an initial dose of about 400 mg gimsilumab on the first day of treatment (Day 1) followed by about 200 mg gimsilumab seven days later (Day 8), wherein the treatment results in a statistically significant decrease in the incidence of mortality by Day 43 after treatment. In certain embodiments, there is a statistically significant decrease in mortality at Day 15 or Day 29 after treatment. In other embodiments, the second dose is omitted if a particular patient(s) is discharged from the hospital after the initial dose or no longer needs supplemental oxygen or ventilatory support. [000137] In addition, the therapy described herein is beneficial to patients meeting the clinical classification criteria for ARDS (ARDS Berlin Definition, 2012) or have clinical evidence of lung injury secondary to COVID-19 as follows. 1. Lung injury is defined as PaO2/FiO2 ≤300 mmHg, without invasive or non- invasive ventilation (or with PEEP or CPAP <5 cm H2O). 2. ARDS is defined as: • Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules; • Respiratory failure not fully explained by cardiac failure or fluid overload; • Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present. • Mild oxygenation: 200 mm Hg, < PaO ₂ /FiO ₂ , ≤300 mm Hg with PEEP or CPAP ≥5 cm H ₂ O. • Moderate oxygenation: 100 mm Hg, < PaO ₂ /FiO ₂ , ≤200 mm Hg with PEEP ≥5 cm H ₂ O. • Severe oxygenation: PaO ₂ /FiO ₂ ≤100 mm Hg with PEEP ≥5 cm H ₂ O. E. EFFICACY [000138] The administration of therapeutically effective amounts of the antigen binding proteins described herein, such as gimsilumab or namilumab, are effective in reducing the morbidity and mortality of lung injury or ARDS. Such efficacy may be measured in a number of ways. [000139] 1. Efficacy as Measured as Decreasing the Incidence of Mortality [000140] The incidence of mortality may be measured by the Cochran-Mantel- Haenszel (CMH) test controlled by country and/or the subjects’ baseline (classified as either lung injury/mild ARDS or moderate/severe ARDS). Mortality may also be measured by the Cox Proportional Model. [000141] As further detailed below, for the therapies described herein, the incidence of mortality may be measured by the logistical regression with the Treatment, country and subjects’ clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]). Mortality may also be measured by the Cox Proportional Model. [000142] In certain embodiments, the therapies described herein decrease mortality of patients with lung injury or ARDS measured by CMH, logistical regression or Cox Proportional Model by at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%. In some embodiments, the decrease is statistically significant. [000143] In another embodiment, the treatment described in Example 3 below, will result in decreased mortality of patients with lung injury or ARDS measured by CMH, logistical regression or Cox Proportional Model by at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%. In some embodiments, the decrease is statistically significant. [000144] 2. Efficacy as Measured by the Incidence and/or Duration of Mechanical Ventilation Use During the Study [000145] The efficacy of the therapies herein may be measured by the incidence of mechanical ventilation use. In some embodiments, the therapies described herein decrease in incidence of mechanical ventilation use by patients with lung injury or ARDS by at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%. In some embodiments, the decrease is statistically significant. [000146] The efficacy of the therapies herein may be measured by the duration of mechanical ventilation use. In some embodiments, the therapies described herein shorten the mechanical ventilation use by patients with lung injury or ARDS by at least 1 day, or at least 2 days, or at least 3 days, or at least 4 days, or at least 5 days, or at least 6 days, or at least 7 days, or at least 8 days, or at least 9 days, or at least 10 days, or at least 11 days, or at least 12 days, or at least 13 days, or at least 14 days. In some embodiments, the reduction is statistically significant. [000147] In some embodiments, the therapies described herein decrease in incidence and shorten duration of mechanical ventilation use by patients with lung injury or ARDS. [000148] 3. Efficacy as Measured by the Number of Days in the ICU [000149] The efficacy of the therapies herein may be measured by the number of days patients with lung injury or ARDS spend in the ICU. In some embodiments, the therapies described herein reduce the number of days patients with lung injury or ARDS spend in the ICU by at least 1 day, or at least 2 days, or at least 3 days, or at least 4 days, or at least 5 days, or at least 6 days, or at least 7 days, or at least 8 days, or at least 9 days, or at least 10 days, or at least 11 days, or at least 12 days, or at least 13 days, or at least 14 days. In some embodiments, the reduction is statistically significant. [000150] 4. Efficacy as Measured by the Number of Days of Inpatient Hospitalization [000151] The efficacy of the therapies herein may be measured by the number of days patients with lung injury or ARDS in inpatient hospitalization. In some embodiments, the therapies described herein reduce the days of inpatient hospitalization by at least 1 day, or at least 2 days, or at least 3 days, or at least 4 days, or at least 5 days, or at least 6 days, or at least 7 days, or at least 8 days, or at least 9 days, or at least 10 days, or at least 11 days, or at least 12 days, or at least 13 days, or at least 14 days. In some embodiments, the reduction is statistically significant. [000152] 5. Efficacy as Measured by Improvement of Sequential Organ Failure Assessment (SOFA) Score [000153] The efficacy of the therapies described herein may be measured by SOFA score. SOFA score is assessed daily while the subject is in the ICU. In some embodiments, the therapies described herein reduce the SOFA score by at least 1 point, or at least 2 points, or at least 3 points, or at least 4 points, or at least 5 points, or at least 6 points, or at least 7 points, or at least 8 points, or at least 9 points, or at least 10 points, or at least 11 points, or at least 12 points, or at least 13 points, or at least 14 points, or at leat 15 points, or at least 16 points, or at least 17 points, or at least 18 points, or at least 19 points, or at least 20 points, or at least 21 points, or at least 22 points, or at least 23 points. In some embodiments, the reduction is statistically significant. [000154] 6. Efficacy as Measured by Improvement of Rating on 7-point Ordinal Scale [000155] The efficacy of the therapies described herein may be measured by the percentage of subjects having each severity rating on the 7-point ordinal scale. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death. In certain embodiments, the status on the 7-point ordinal scale is assessed daily while hospitalized, on the day of discharge (DoD), and on Days 15, 22, 29, 36, and 43 after treatment. Change in ordinal scale at specific time points are summarized by proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point worsening). For instance, the treatments described herein, including in Example 3 below, result in a statistically significant number of patients who have a 1-, 2-, 3-, or 4-point improvement on the 7-point ordinal scale. In one embodiment, at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75% of treated patients have at least a 1 level improvement after treatment. In some embodiments, such improvement is statistically significant. [000156] In another embodiment, at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75% of treated patients have at least a 2 level improvement after treatment. In some embodiments, such improvement is statistically significant. [000157] In yet another embodiment, at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75% of treated patients have at least a 3 level improvement after treatment. In some embodiments, such improvement is statistically significant. [000158] Further, at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75% of treated patients have at least a 4 level improvement after treatment. In some embodiments, such improvement is statistically significant. [000159] 7. Efficacy as Measured by National Early Warning Score (NEWS) [000160] NEWS employs the following parameters. [000161] National Early Warning Score Physiological 3 ^{2 1 0 1 2 3} [000162] These parameters can be obtained from the hospital chart using the last measurement prior to the time of assessment. This is recorded for the day obtained (i.e., on Study Day 3, the Day 3 score is obtained and recorded as Day 3). This should be evaluated at the first assessment of a given study day. [000163] The therapies described herein result in patient improvement as measured by NEWS, for instance, a score of less than or equal to 4 after treatment and which was maintained for 24 hours. In some embodiments, the improvement is statistically significant. [000164] In certain embodiments, the therapies described herein result in patient NEWS scores improving from baseline by at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%. In some embodiments, the improvement is statistically significant. [000165] In another embodiment, the treatment described in Example 3 below will result in patient NEWS scores improving from baseline by at least 1%, or at least 2%, or at least 3%, or at least 4%, or at least 5%, or at least 6%, or at least 7%, or at least 8%, or at least 9%, or at least 10%, or at least 11%, or at least 12%, or at least 13%, or at least 14%, or at least 15%, or at least 16%, or at least 17%, or at least 18%, or at least 19%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%. In some embodiments, the improvement is statistically significant. [000166] In yet other embodiments, the efficacy of the therapies disclosed herein may be measured by one or more of the following: · Assessment of change from Baseline to Day 15 (if hospitalized) and at DoD in the following parameters: o SpO2/FiO2 ratio by day o GFR, calculated · Oxygenation-free days in the first 28 days (to Day 29). · Incidence and duration of new or increased oxygen use during the study. · Ventilator-free days in the first 28 days (to Day 29). · Incidence and duration of new mechanical ventilation use during the study. · Number of days of inpatient hospitalization. In certain embodiments, the therapies disclosed herein result in a statistically significant number of patients who show improvement in one or more of these efficacy assessments. [000167] The time-to-event endpoints are summarized with Kaplan Meier curves and 95% confidence bounds by the treatment. The Cox Hazard Proportional model with treatment, country, and subject's clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS) as model terms are used. The hazard ratio of gimsilumab versus placebo is presented with 95% CI and p-values. [000168] Duration of event (e.g., duration of mechanical ventilation) is summarized according to median days with quartiles. The Wilcoxon rank test is used for the treatment difference. [000169] Incidence data (e.g., incidence of new or increased oxygen use) are summarized as a percent with 95% confidence intervals. The CMH test controlled by country and subject's clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS) is used for treatment difference. The odds ratio of gimsilumab versus placebo, 90% CIs and p- values is provided. [000170] The continuous variables, including the changes from baseline, are summarized by the treatment with the means, standard deviations, medians and the ranges. The Mixed Model with Repeated Measurements (MMRP) /Analysis of Covariance (ANCOVA) with the treatment, country, subject's clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS), and visit as the model term, and baseline value as the covariate are used for the treatment difference. The least square means, standard errors, 95% CIs and p- values are presented. F. EXAMPLES EXAMPLE 1: GENERATION OF HUMAN ANTIBODIES TO HUMAN GM-CSF [000171] Human anti-GM-CSF antibodies were generated as described in U.S. Pat. Nos. 10,023,632, 8,017,748, and 9,067,993. The exemplary GM-CSF antagonist used in the following Examples 2-5 and 7 is the human anti-GM-CSF antibody designated “gimsilumab.” Gimsilumab (KIN-1901, formerly named MORAb-022) has the following amino acid sequence characteristics: heavy chain (HC) comprising SEQ ID NO:1; light chain (LC) comprising SEQ ID NO:2; heavy chain complementarity determining region 1 (HCDR1) comprising SEQ ID NO:3; HCDR2 comprising SEQ ID NO:4; HCDR3 comprising SEQ ID NO:5; light chain complementarity determining region 1 (LCDR1) comprising SEQ ID NO:6; LCDR2 comprising SEQ ID NO:7; and LCDR3 comprising SEQ ID NO:8. [000172] Gimsilumab is a fully human immunoglobulin G1/κ (IgG1/κ) monoclonal antibody (mAb) directed to human granulocyte macrophage-colony-stimulating factor (GM- CSF). Gimsilumab binds to and neutralizes the biological activities of GM-CSF with high affinity and potency. GM-CSF, an important hematopoietic growth factor and immunomodulatory cytokine, is believed to a key mediator of cytokine storm and to contribute to SARS-CoV-induced ARDS. For example, GM-CSF was identified as a cytokine that is upregulated in the serum of COVID-19 patients and SARS-CoV-2 infection induced activation of immune cells that secreted large amount of GM-CSF. Gimsilumab may be an effective treatment to slow or reverse lung infiltration by highly inflammatory monocyte-derived macrophages. [000173] The exemplary GM-CSF antibody used in the following Examples 6 and 7 is the human anti-GM-CSF antibody designed “namilumab.” Namilumab is a human IgG1 monoclonal antibody. Like gimsilumab, namilumab binds to and neutralizes the biological activities of GM-CSF with high affinity and potency. Namilumab (formerly named MT203 or AMG203) has the following amino acid sequence characteristics: heavy chain (HC) comprising SEQ ID NO:18; light chain (LC) comprising SEQ ID NO:19; HC variable (HCV) comprising SEQ ID NO:9; heavy chain variable (LCV) comprising SEQ ID NO:10; heavy chain complementarity determining region 1 (HCDR1) comprising SEQ ID NO:11; HCDR2 comprising SEQ ID NO:12; HCDR3 comprising SEQ ID NO:13; light chain complementarity determining region 1 (LCDR1) comprising SEQ ID NO:14; LCDR2 comprising SEQ ID NO:15; and LCDR3 comprising SEQ ID NO:16. EXAMPLE 2: PHARMACOKINETICS AND SAFETY OF THE ANTI-GM-CSF ANTIBODY IN HUMANS [000174] A Phase 1 first-in-man study (MORAB-022-001) was conducted to assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single-dose intravenous gimsilumab in healthy subjects and subjects with rheumatoid arthritis (RA). Doses ranged from 0.0085 to 10 mg/kg in that study, with the highest doses (0.36 mg/kg to 10 mg/kg) administered to subjects with RA. Study MORAB-022-001 showed the PK were dose- proportional over the entire dose range, with no differences noted between healthy subjects and subjects with RA. Although adverse events (AEs) (headache, nasopharyngitis, flu-like symptoms) were encountered more frequently in the gimsilumab group, they were graded mild to moderate and were not dose-related. [000175] Subcutaneous administration of gimsilumab was evaluated in ongoing study KIN-1901-1001. Single- and repeat-dose (once weekly for 4 doses) gimsilumab was administered to healthy volunteers to evaluate safety and pharmacokinetics. Based on a blinded safety data review, gimsilumab was well tolerated with no serious adverse events (SAEs), the majority AEs (67%) were injection site reactions (erythema, tenderness, bruising). [000176] A population PK model of IV gimsilumab was developed from the IV first- in-human study. Based on this model, simulations were conducted to a select an appropriate dose regimen. While the prior study using IV gimsilumab utilized mg/kg dosing, a “flat dose” regimen (not body weight adjusted) was selected for this study to simplify administration in this setting. Simulations accounted for a range in subject body weight to select an appropriate flat dose. Using this model, a dose of 400 mg on Day 1 results in a median trough serum concentration of 29 µg/mL on Day 8. Based on the expected variability in exposure and range in subject body weight, the serum trough concentration at the lower bound of the 80% prediction interval (i.e., the 10th percentile) is expected to be about 20 µg/mL (Fig. 1), i.e., 90% of subjects are expected to achieve serum concentrations above the target. A second dose of gimsilumab 200 mg on Day 8 maintains the trough concentration at these levels for an additional week. Based on the duration of ICU time in both survivors and non-survivors from a Chinese cohort of about seven days (Zhou et al., Pre-Print. 2020. https://doi.org/10.1101/2020.02.12.945576), two doses, i.e., a 14-day treatment period, was considered appropriate for this study. If subjects are discharged from the hospital or no longer in need of supplemental oxygen or ventilatory support for more than 48 hours, the planned Day 8 dose will be omitted. [000177] The predicted exposure after gimsilumab 400 mg IV on Day 1 (the highest exposure expected during the study) is approximately half that observed at 10 mg/kg IV in subjects with RA (Table 3). The expected Cmax at the 90 ^th percentile is also expected to be less than the geometric mean C _max observed previously at 10 mg/kg IV. In addition, the predicted exposure margins after 400 mg IV compared to the monkey 26-week IV toxicology study is presented in Table 3. The no-observed-effect level (NOEL) in the monkey was 200 mg/kg IV once weekly; the NOEL was the highest dose tested. The exposures observed in monkeys were at least 40× greater than those expected in the current study. Thus, given the observed safety profile and the pharmacologic activity at the expected exposures in the current study, gimsilumab 400 mg Day 1 and 200 mg Day 8 was selected for the present study. Table 3. Predicted Gimsilumab Exposure and Exposure Margins after Gimsilumab 400 mg IV Compared to Highest IV Dose Studied in Study MORAb-022-001 in Humans and the NOEL IV Dose Studied in Cynomolgus Monkeys

Predicted Exposure Predicted Exposure M i X f l bMedian predicted exposure after planned dose divided by observed mean at 200 mg/kg IV in male and female monkeys at Day 176 (gender averaged Cmax = 11,800 µg/mL; AUC0-∞ = 731,000 µg.h/mL) [000178] Gimsilumab vials are diluted in 0.9% saline, the resultant concentration (about 4 mg/mL) is similar or less than those demonstrated to be safe in monkey IV toxicology studies. Gimsilumab is infused over a 1-hour period, resulting in a rate no higher than 400 mg/h. This rate is similar to the highest rate previously administered to subjects with RA, that was well tolerated. EXAMPLE 3: DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF GIMSILUMAB IN SUBJECTS WITH LUNG INJURY OR ARDS SECONDARY TO CORONAVIRUS DISEASE 2019 (COVID-19) A. Introduction and Study Design [000179] Applicant will perform a randomized, double-blind, placebo-controlled study (KIN-1901-2001) in male and/or female adult subjects who are at risk of developing, or have developed, ARDS consequent to moderate to severe COVID-19. There will be two treatment arms, one receiving gimsilumab, and one receiving placebo of approximately 270 total evaluable subjects, with 135 subjects per treatment arm. Efficacy, safety, tolerability, PK, and PD of gimsilumab will be assessed in hospitalized adult subjects diagnosed with COVID- 19. [000180] An individual will be eligible for inclusion in this study only if all the following criteria are met. 1. Male or non-pregnant female age ≥ 18 years. 2. Subject (or legally authorized representative) is able and willing to provide written or verbal informed consent, which includes compliance with study requirements and restrictions listed in the consent form. 3. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other approved clinical testing prior to randomization, 4. CRP ≥50 mg/L or serum ferritin ≥1,000 ng/mL. Results from CRP and ferritin tests performed within 8 days of randomization are acceptable for enrollment, 5. Radiographic evidence of bilateral infiltrates, 6. Subject has clinical evidence of lung injury (defined as (1) requiring supplemental oxygen ≥ 4L O2 to maintain ≥ 92% SpO2, or (2) PaO2/FiO2 ratio ≤300 mmHg (can be imputed)), or meets clinical classification criteria for ARDS (ARDS Berlin Definition, 2012), secondary to COVID-19. 7. Female subjects must agree to use an approved highly effective birth control (BC) method (< 1% failure rate per year) throughout the study (until completion of the Day 85 Follow-up Visit), unless documented to have a reproductive status of non-childbearing potential or are postmenopausal: · Non-childbearing potential defined as pre-menopausal female with medical history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), or hysterectomy; hysteroscopic sterilization, · Postmenopausal defined as 12 months of spontaneous amenorrhea; with follicle stimulating hormone (FSH) confirmation. · Woman of childbearing potential (WCBP) who is already using an established method of highly effective contraception or agrees to use one of the allowed BC methods, for at least 28 days prior to the start of dosing to sufficiently minimize the risk of pregnancy throughout study participation (until completion of the Day 85 Follow-up Visit). 8. Males who are sexually active must agree to use one of the allowed BC methods. Male subjects must also agree to sufficiently minimize the risk of pregnancy throughout study participation (until completion of the Day 85 Follow-up Visit). [000181] Subjects will be excluded if they exhibit any of the following: 1. Subject requires norepinephrine at a dose of >0.5 mcg/kg/min, or equivalent. 2. Subject has been intubated for >72 hours. 3. Evidence of life-threatening dysrhythmia (e.g., ventricular tachycardia (VT), ventricular fibrillation (VF)), or cardiac arrest on presentation. 4. Evidence of new or preexisting decompensated heart failure. 5. At the time of screening, subject is anticipated to require ECMO. 6. Absolute neutrophil count < 1,000 per mm ³ . 7. Platelet count <50,000 per mm ³ . 8. History of known anti-GM-CSF autoantibodies (autoAb) or pulmonary alveolar proteinosis, 9. Severe chronic respiratory disease (e.g., known chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), interstitial lung disease (ILD)) requiring baseline oxygen therapy or mechanical ventilation pre hospitalization. 10. Known or suspected active and untreated active tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C infection. 11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN). 12. eGFR <30 mL/min/1.73m ² (MDRD equation) or requiring hemofiltration or dialysis. 13. Use of any immunomodulatory (e.g., anti-IL-1, anti-IL-6R, anti-TNF, inhibitors of complement signaling), cell therapies (e.g., mesenchymal stem cells), or small molecule JAK inhibitors within the past 7 days or within five half-lives (whichever is longer), or planned use of any of these agents from Screening until Day 43 of the study, unless approved by the Medical Monitor. The following will be allowed/disallowed: · Immunomodulatory biologics for COVID-19 treatment are excluded and should not be used until Day 43 unless discussed with the Medical Monitor. Other non-biologic immunomodulators (non-JAK inhibitors), e.g., medicines for previous transplantation, or disease modifying anti- rheumatic drugs (DMARDS), and have had a stable dose for ≥8 weeks are permitted. · Subjects who have been treated with convalescent plasma (CP) prior to enrollment are eligible if the subject continues to meet all inclusion criteria at screening. Ongoing therapy with CP is allowable if clinically indicated in the view of the treating physician or the Investigator. · The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the subject continues to meet all inclusion criteria at screening. 14. Ongoing Chronic (≥4 weeks) use of corticosteroids >10 mg/day of prednisone or equivalent at the time of randomization. A corticosteroid dose that has been tapered to 10 mg or less within 14 days of randomization is also prohibited. 15. Pregnancy and/or breast feeding. 16. Unable to receive invasive or non-invasive ventilatory support. 17. Moribund condition in the opinion of the clinical team. [000182] A schematic of the study design is presented in Fig. 2. Randomization of the patients will be stratified by: · Country · Subject's clinical status at Baseline o Lung injury/mild ARDS o Moderate/severe ARDS B. Arms and Study Treatment [000183] Each subject will participate for approximately six weeks, with a two-week Treatment Period (last dose on Day 8) and a four-week follow up period. A summary of the treatment arms is presented in Table 4. Table 4. Treatment Arms The Day 8 dose is omitted if the subject is discharged from the hospital or is no longer in need of supplemental oxygen or ventilatory support for more than 48 hours. [000184] Study treatments are presented in Table 5. Table 5. Treatment Descriptions C. Study Assessments [000185] Assessments of the Study Treatment will be performed as stated in Table 6 below.

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O N ⁷⁴⁰⁸ A C V O N W ⁶ ₇₀₄₂ 63 ⁷⁴⁰⁸⁶ ₇₀₄₂ 64 D. Subject Populations and Analyses [000186] The Intent-to-Treat (ITT) Population will include all randomized subjects who receive any amount of study drug. The ITT subjects will be analyzed according to randomized treatment, irrespective of whether they have prematurely discontinued. Subjects who withdraw from treatment and/or the study will be followed for Day 43 all-cause mortality. All efficacy analyses will be performed using the ITT Population. [000187] The Safety Population (SP) will include all randomized subjects who receive any amount of study drug. The SP will be analyzed according to the treatment received. This set will be used for the safety analyses. [000188] The per-protocol (PP) Population will include all subjects in the ITT Population who complete the Day 43 Visit with no protocol violations. The PP Population will be used for supportive analyses of the efficacy measurements. [000189] In general, all the continuous variables, including the changes from Baseline, will be summarized by the treatment with the mean, standard deviation (SD), median and the range. The Mixed Model with Repeated Measurements (MMRM) /Analysis of Covariance (ANCOVA) model with the treatment, country, subject’s clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS), and visits as the model term are used to test for the significance of the treatment difference. The least square means, standard errors, 95% CIs and p-values will be presented. [000190] All the categorical variables will be summarized by the treatment with the numbers and percentages of the subjects, and the treatment difference, the odds ratio and 95% CI will be tested by using logistical model (Ge M, Durham LK, and Meyer DR. Covariate- adjusted difference in proportions from clinical trials using logistic regression and weighted risk differences. Drug Information Journal 2011;45:4) with the Treatment, country, and subject’s clinical status at baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) for binary outcome. The CMH test will be used for other categorical outcomes. [000191] The time to event endpoints will be analyzed by using the Cox Proportional Hazard model with the treatment, subject’s clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS), and country as the model term. The hazard ratio of gimsilumab versus placebo will be presented with 95% CI and p value from the model. The Kaplan-Meier curves of the time to events will be presented for treatments on each endpoint. [000192] Subgroup analyses for the primary outcomes will evaluate the treatment effect across the following subgroups: country, subject's clinical status at Baseline (lung injury/mild ARDS or moderate/severe ARDS), age, and sex. A forest plot displays confidence intervals across subgroups. Interaction tests are conducted to determine whether the effect of treatment varies by subgroup. E. Therapeutic Endpoints 1. Primary Endpoint [000193] The primary endpoint of the study will be Incidence of mortality by Day 43. The primary analysis of the primary endpoint will be performed by using the logistical regression with the Treatment, country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]). The subjects who died by Day 43 (by Day 169) will be summarized by the numbers and percentages, difference of the percentages, the odds ratio and its 95% CI presented for gimsilumab versus placebo, and p-value. [000194] The secondary analysis of the primary endpoint will be conducted by using the Cox Proportional Hazard model with treatment, country and subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS] on the time to death. The median of the time to event from Kaplan-Meier curves will be presented for each treatment, and the hazard ratio of the gimsilumab dose level versus placebo will be presented with 95% CI, and p-values. [000195] The Per-Protocol (PP) Population will be used for the primary and secondary analysis of the primary endpoint as the supportive analyses. [000196] The interim analysis will be conducted when 60 subjects have been treated and have completed through Day 15; the independent Data Monitoring Committee (DMC) will review the data for safety and futility and provide their recommendations. The second interim analysis will be conducted when 100 subjects have completed at least the Day 29 Visit for non- mortality endpoints and have the data for the endpoint of mortality (by Day 43). The objectives of the second interim analysis will be to stop the study by superiority, futility, or perform the sample size re-estimation. For controlling overall two-sided alpha of 0.05 overall for the final analysis on the primary endpoint of Mortality Day 43, 0.001 of the alpha will be used for the superiority comparison during the second interim analysis, and 0.049 will be used for the final analysis for Day 43. The weighted average of two summary measures by Cui L, Hung HM, Wang [Cui L, Hung HM, Wang SJ. Modification of sample size in group sequential clinical trials. Biometrics.1999;55:853–7.] will be used, one based on the data collected in the interim analysis, and the other based on the data collected after the interim. .2. Secondary Endpoints [000197] Key secondary endpoints of the study are: · Proportion of subjects who survived and were not requiring mechanical ventilation on Day 29 · Mechanical ventilation-free days by Day 29 · Time to hospital discharge by Day 43 [000198] Additional secondary endpoints of the study are: · Incidence of mortality by Days 15, 22, 29, 85, and 169 (End-of-Study [EoS]). · Proportion of subjects who survived and were not requiring mechanical ventilation on Days 15, 22, and 43. · Mechanical ventilation-free days for all subjects by Days 15, 22, and 43 · ICU-free days for all subjects by Days 15, 22, 29, and 43. · Incidence of mechanical ventilation use for all subjects by Days 15, 22, 29, and 43. · Incidence of ICU use for all subjects by Days 15, 22, 29, and 43 · Time to death by Day 43 and Day 169 (EoS) · NEWS assessed daily while hospitalized · SOFA score, and each of the components, assessed daily while in the ICU · The percentage of subjects reporting each severity rating on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone) · Status on the 7-point ordinal scale, assessed daily while hospitalized and, if discharged from hospital, on Days 15, 22, 29, 36, 43, 85, and 169 (assessed by phone) · Time to clinical improvement by 2 points on the 7-point ordinary scale · Change from Baseline in SpO2/FiO2, assessed daily while hospitalized · Incidence and duration of oxygen use during the study · Change from Baseline in viral load as measured by quantitative PCR test on Days 2, 9, and DoD · Change from Baseline in D-dimer, cardiac troponin I, LDH, ferritin, and CRP · Serum gimsilumab concentrations · Analysis of anti-gimsilumab antibodies (ADAs). [000199] Secondary endpoints will be analyzed as follows: [000200] Incidence data (e.g., incidence of new or increased oxygen use) will be summarized as a percent with 95% CIs. The logistic regression model with treatment, country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) will be used for the odds ratio of gimsilumab versus placebo, 95% CIs and p-values. [000201] Change in ordinal scale at specific time points will be summarized by proportions (e.g., proportion who have a 1-, 2-, 3-, or 4-point improvement or 1-, 2-, 3-, 4-point worsening). The CMH test on combined subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) will be used for treatment difference. The odds ratio of gimsilumab versus placebo, 95% CIs and p-values will be provided. [000202] Duration of event free (e.g., mechanical ventilation free days) will be summarized according to median days with quartiles. The Wilcoxon rank test will be used for the treatment difference. [000203] The continuous variables, including the changes from baseline, will be summarized by the treatment with the mean, standard deviation (SD), median, and the range. PK summaries will include geometric mean and geometric coefficient of variation. The Mixed Model with Repeated Measurements (MMRP)/Analysis of Covariance (ANCOVA) with the treatment, country, subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]), and visit as the model term, and baseline value as the covariate will be used for the treatment difference. The least square means, standard errors, 95% CIs and p- values will be presented. [000204] The time-to-event endpoints will be summarized with Kaplan Meier curves and 95% confidence bounds by the treatment. The Cox Proportional Hazard model with treatment, country, and subject’s clinical status at Baseline ([lung injury/mild ARDS] or [moderate/severe ARDS]) as model terms will be used. The hazard ratio of gimsilumab versus placebo will be presented with 95% CI and p-values. 3. Exploratory Endpoints [000205] Exploratory endpoints of the study are: · Change from Baseline in the cytokine panel and serum SP-D. · Change from Baseline in LIS (if performed). · Change from Baseline in chest radiographic assessment (if performed). · Change from Baseline in P/F ratio, if performed. · Incidence and duration of ECMO use. · Change from Baseline in left ventricular ejection fraction (LVEF) (when measured). · Change from Baseline in estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease (MDRD) equation), assessed when central clinical safety laboratory measurements are collected during hospitalization. 4. Additional Endpoints [000206] Safety endpoints – Safety and tolerability, including assessment of clinical safety laboratory measurements, physical examinations, vital signs, concomitant medications; cumulative incidence of adverse events (AEs), serious adverse events (SAEs), and severe AEs. [000207] Safety is assessed based on the SP for AEs, laboratory parameters, physical examination, vital signs, and clinical chemistries throughout the duration of the study. The safety analyses include descriptive summaries by treatment arm of AEs. The number and percentage of participants reporting AEs and SAEs are presented. Adverse events are categorized by system organ class (SOC) and preferred term (PT) and summarized by the number of participants (and percentage) with at least one event, and the number of events. Adverse events are also summarized by seriousness, grade, and study drug relationship for all participants. The continuous variables, including the changes from Baseline, are summarized by descriptive statistics: mean, SD, and the range. The categorical variables, such as normal/abnormal are summarized by the numbers and percentages at each visit, and the shift table from Baseline to each visit are presented. [000208] Pharmacokinetic Endpoints – Serum gimsilumab concentration at time points as specified in the Schedule of Assessments. [000209] Pharmacodynamic Endpoints – Changes from Baseline in serum CRP, cytokine, and SP-D concentrations will be measured at time points as specified in the Schedule of Assessments (Table 6). [000210] In various embodiments, the study will result in decreased morbidity and mortality, and improvements in the secondary endpoints and other endpoints without serious AEs. Further information regarding the study protocol is described below. [000211] Outcomes of the study in general patient population and a subpopulation of patients mechanically ventilated at baseline are shown in Examples 6 and 7, respectively. EXAMPLE 4: Statistical Analysis Plan to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome (ARDS) Secondary to Coronavirus Disease 2019 (COVID-19) A. Introduction and Study Design [000212] In a randomized, double-blind, placebo-controlled study of gimsilumab for the treatment of lung injury or ARDS secondary to COVID-19 (Study KIN-1901-2001), a total of 270 subjects are planned to be treated with IV gimsilumab on day 1 (400mg) and day 8 (200mg) or matching IV placebo (saline solution on days 1 and 8). This study consists of a 2- week Treatment Period and a 22-week Follow-up Period and will include subjects with moderate-to-severe disease. Efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of gimsilumab will be assessed in hospitalized adult subjects diagnosed with COVID-19. [000213] A schematic of the study design is presented in Fig. 2. Subjects will be assessed daily while hospitalized. Follow-up assessments are planned through Week 24, for a total study duration post-randomization of approximately 169 days (24 weeks). Follow-up visits at Days 15, 22, 29, 36, 43, 85 and 169 will be performed by phone if the subject has been discharged from the hospital. All subjects will undergo a series of efficacy, safety, and laboratory assessments. [000214] Each subject will participate for approximately 24 weeks, with a 2-week Treatment Period (last dose on Day 8) and a 22-week Follow-up Period. Treatment Arms for KIN-1901-2001: Arm 1: Gimsilumab (400 mg) as a single IV infusion on Day 1 followed by a single 200 mg IV infusion on Day 8* (N=135) Arm 2: Placebo (0.9% saline solution) IV infusion on Day 1 and Day 8* (N=135) *The Day 8 dose will be omitted if the subject is discharged from the hospital or is no longer in need of supplemental oxygen or ventilatory support for >48 hours. [000215] There will be two interim analyses (IA): 1 ^st IA: For safety and futility when 60 subjects have completed treatment and completed through study Day 15 2 ^nd IA: For safety, superiority, and futility when 100 subjects have completed the study Day 29 Visit (for non-mortality endpoints) or have died (mortality data) by Day 43. The sample size re-estimation will be performed to maintain the conditional power of 80% the primary analysis of Mortality by Day 43. [000216] This study will have two database locks. The database will be locked first when all subjects complete the Day 43 Visit, discontinue from the study early, or meet the primary mortality endpoint. The second lock will occur when the last subject completes the Day 169/ EoS visit, discontinue from the study early, or died up to Day 169. Study unblinding will occur at the first database lock. [000217] All analyses described in this SAP will be performed at the 1st database lock. For the 2nd lock, all safety analyses will be performed but efficacy analyses without new data (e.g. assessments only collected during hospitalization if all subjects have been discharged by 1st database lock) may not be performed again. [000218] The comparisons between the treatment arms will have approximately 83% power and overall two-sided alpha level 0.05 (the equivalent one-sided overall significance level 0.025 will be used in the remainder of this SAP) to demonstrate a statistically significant reduction in mortality by Day 43 for gimsilumab compared to placebo when assuming true proportions of 15% and 30%, respectively and a superiority / futility interim analysis. [000219] The study will enroll at least 40%, but no more than 60%, of total patients in each of the 2 categories of clinical status: ([lung injury/mild ARDS] or [moderate/severe ARDS]) at Baseline, which will be used as the stratified factor in the randomization. [000220] Use of tocilizumab or any other immunomodulatory biologic (e.g., anti-IL- 1, anti-IL-6R, anti-TNF), cell therapies (e.g., mesenchymal stem cells), or small molecules (e.g., JAK inhibitors) is prohibited during the study. Additional prohibited medications may also be defined during blinded data review prior to general study unblinding. The number and percentages of the subjects using such medications will be summarized by treatment groups, and the impact on efficacy and safety will be analyzed by subgroup analyses. B. Study Objectives [000221] This statistical analysis plan (SAP) provides a detailed description of the statistical methods and analyses to be carried out in support for study KIN-1901-2001. The primary objective is to evaluate the impact of intravenous (IV) treatment with gimsilumab on mortality in subjects with lung injury or ARDS secondary to COVID-19. The key secondary objectives are: (i) to assess the effect of gimsilumab on ventilation requirements, and (ii) to assess the effect of gimsilumab on overall duration of hospitalization Additional secondary objectives are: (i) to assess the effect of gimsilumab on the need for Intensive Care Unit (ICU) level of care, (ii) to assess the effect of gimsilumab as measured by the National Early Warning Score (NEWS), (iii) to assess the effect of gimsilumab as assessed by the Sequential Organ Failure Assessment (SOFA) score, (iv) to assess the effect of gimsilumab as measured by the 7-point ordinal scale, (v) to assess the effect of gimsilumab on peripheral capillary oxygen saturation / fraction of inspired oxygen (SpO2/FiO2), (vi) to assess the effect of gimsilumab on oxygenation requirements, (vii) to assess changes in on-treatment viral load, (viii) to assess the effect of gimsilumab on biomarkers of inflammation, (ix) to determine the pharmacokinetic (PK) properties of gimsilumab, (x) to assess the immunogenicity of gimsilumab, and (xi) to determine the safety and tolerability of gimsilumab. [000222] The exploratory objectives are: (i) to explore the effect of gimsilumab on serum cytokine concentrations and surfactant protein D (SP-D), (ii) to explore the effect of gimsilumab on other measurements of lung injury that may be performed during standard care (e.g., Lung Injury Score [LIS], chest radiography, PaO2/FiO2 [P/F ratio], need for extracorporeal membrane oxygenation [ECMO]), (iii) to explore the effect of gimsilumab on cardiac function (if measured), and (iv) to assess the effect of gimsilumab on renal function. C. Endpoints 1. Efficacy Variables [000223] (i) Primary: Mortality by Day 43 [000224] (ii) Key Secondary are proportion of subjects who survived and not requiring mechanical ventilation on Day 29, mechanical ventilation-free days by Day 29, and time to hospital discharge. [000225] (iii) Additional Secondary are: · Mortality by Days 15, 22, 29, 85, and 169 (EoS) · Proportion of subjects who survived and were not requiring mechanical ventilation on Days 15, 22, and 43 · Mechanical ventilation-free days for all subjects by Days 15, 22, and 43. · ICU-free days for all subjects by Days 15, 22, 29, and 43 · Incidence of mechanical ventilation use for all subjects Days 15, 22, 29, and 43. · Incidence of ICU use for all subjects Days 15, 22, 29, 43 · Time to death by Day 43 and Day 169 (EoS) · NEWS assessed daily while hospitalized · SOFA score and each of the components assessed daily while in the ICU · Status on the 7-point ordinal scale daily while hospitalized and on Days 15, 22, 29, 36, 43, 85, and 169 if discharged · Time to clinical improvement · Change from Baseline in SpO2/FiO2 assessed daily while hospitalized · Incidence and duration of oxygen use during the study · Change from Baseline in viral load as measured by quantitative polymerase chain reaction (PCR) test on Days 2, 9, and Day-of-discharge (DoD) · Change from Baseline in D-dimer, cardiac troponin I, lactate dehydrogenase (LDH), ferritin, procalcitonin, and C-reactive protein (CRP) on Days 4, 8, and DoD (and Days 15, 22, 29, 36, and 43 if hospitalized) · Serum gimsilumab concentrations on Days 1, 8, and DoD · Anti-gimsilumab antibodies (ADAs) on Day 1 and DoD (and Days 15, 29, and 43 if hospitalized) 2. Safety Variables · Physical examinations · Vital signs (supine blood pressure [BP] and pulse, oral body temperature, respiratory rate) · Clinical laboratory tests (hematology, clinical chemistry, and urinalysis parameters) · Adverse event (AE) assessments · Concomitant medication assessments [000226] The above safety variables will be summarized by Day 43 and Day 169/EoS. 3. Exploratory Variables · Change from Baseline in the cytokine panel on Days 4, 8, and DoD (and Days 15 and 29 if hospitalized) · Change from Baseline in LIS (if performed) daily while hospitalized · Change from Baseline in chest radiographic assessment (if performed) · Change from Baseline in P/F ratio (if performed) daily while hospitalized · Incidence and duration of ECMO use · Change from Baseline in left ventricular ejection fraction (LVEF) (when measured) · Change from Baseline in eGFR [Modification of Diet in Renal Disease (MDRD) equation], assessed when central clinical safety laboratory measurements are collected during hospitalization D. Study Periods [000227] This study has two periods, the treatment period and the follow-up period. The follow-up period will be divided into two for analysis purposes, the first for follow-up through Day 43 and the second for Day 44 through the end-of study. Some assessments will only be done while subjects are hospitalized, because of this some endpoints during each period will not be available for all subjects. The hospitalization period will contain all assessments during either the treatment period or follow-up period that occur before the subject is discharged. The discharge period will cover the time starting the day after hospital discharge through the end-of-study. Differences in time at risk will also be taken to account at the endpoint level and each endpoint be analyzed using methods appropriate to its planned collection pattern. Medical events and medications will be classified into study periods using their start dates. [000228] The following definitions will be applied: Treatment period (Day 1 – Day 15): Starts on first dose date and ends at the earliest of first dose date + 14 and end of study date. Follow-up period 1 (Day 16 through Day 43): Starts on first dose date + 15 and ends at the Day 43 Visit date. Follow-up period 2 (Day 44+): Starts on first dose date + 43 and ends at the end of study date. Overall: Treatment period, follow-up period 1 and follow-up period 2 combined. Overall - Hospitalized: Study Day 1 to date of discharge. This period will include all assessments that were taken while the subject was hospitalized. Overall – After Discharge: Day of discharge through end of study. This period starts at date of discharge + 1 and ends at the end of study date. Where, · First dose date: Day 1, date first dose of study drug received. · End of study date: date of End-of-Study visit (Day 169/ EoS) if subject completes the study · or date of early withdrawal if subject discontinues early or date of death. · Date of discharge: date subject is discharged from the hospital. · Study Day: <Assessment Date> - first dose date + 1 if <Assessment Date> is on or after first · dose date. <Assessment Date> - first dose date, if <Assessment Date> is before first dose date. · Study drug: gimsilumab or placebo · Study treatment: administration of study drug on Day 1 and Day 8 (as required per protocol). E. Study Visits and Windowing [000229] Baseline: the last available pre-treatment assessment. All assessments should have time collected. If time is not collected and date of assessment is the same as the first dose date, then assessment will be assumed to be collected prior to treatment unless schedule of assessments and protocol indicate planned collection is always after dosing. Day-of-Discharge (DoD): day when subject is discharged from the hospital. Early Termination (ET): day when subject withdraws from the study before completion. End-of-Study (EoS): the end of study visit is at Day 169 (24 weeks after first dose) for subjects who complete the study. Study Visits: Planned study visits are detailed in Table 4-1. Planned study visits that occur outside of their protocol defined window will be analyzed as reported and there will no attempt to correct visits that fall outside their planned time frame by applying analysis visit windows. Unscheduled visits will be assigned to a study visit if they fall into the study windows. Unscheduled visits that do not fall into scheduled study visit window will be included when classifying endpoints across a period (e.g. maximum value during study period) but will not be reported in by visit summaries. [000230] In the case of multiple assessments on the same visit the following rules will apply: · If more than one assessment occurs during the same nominal visit time window of the planned visit, select the record closest to the nominal day for that particular visit day. · If there are two assessments that are equidistant from the nominal planned visit day, the data of the assessment after the scheduled study day will be used. · If multiple measurements are all taken on the same day the earliest measurement of this day will be used. Table 4-1: Study Visit Windowing

*no window will be applied for assessments collected daily during hospitalization [000231] Every effort will be made to collect complete dates for all study assessments. The following date imputation rules will be applied for missing or partial dates: · If month and year available, set start date to latest of (1st of the month, first dose date), if end date is complete and imputed start date > end date, set imputed start date to end date – 1. · If year available: Set start date to January 1st of year recorded, if end date is complete and imputed start date > end date, set imputed start date to end date – 1. · If start date is completely missing, set to first dose date, if end date is complete and imputed start date > end date, set imputed start date to end date – 1. · If any imputed date results in an improbable date (e.g. date occurs in the future, date occurs after subject died), set to first dose date. F. Analysis Sets [000232] The Full Analysis Set (FAS) consists of all subjects randomized regardless of whether they received study treatment. Subjects will be summarized and analyzed ‘as randomized’ i.e. by randomized treatment group. If a subject is stratified incorrectly, ‘randomized stratum’ will be used rather than ‘actual stratum’. Summaries of study disposition, protocol deviations and by-subject listings (unless otherwise specified) will be based on the FAS. Efficacy summaries and analyses will be based on the FAS. [000233] The efficacy summaries and analyses will be based on the intent-to-treat (ITT) analysis set, which is defined as all randomized subjects who received any amount of study drug. Subjects will be summarized and analyzed ‘as randomized’ i.e. by randomized treatment group. If a subject is stratified incorrectly, ‘randomized stratum’ will be used rather than ‘actual stratum’. [000234] For the primary and key secondary efficacy endpoints, a sensitivity analysis will be performed on the per-protocol analysis set to assess the robustness of the study conclusions to the choice of analysis set. The per-protocol population is defined as all subjects in the ITT analysis set who complete the study with no major protocol deviations. A blinded data review will occur prior to the first database lock to decide the subjects being excluded from the per-protocol analysis set. [000235] The safety summaries and analyses will be based on the safety analysis set. The safety analysis set is defined as all randomized subjects who received any amount of study drug. Subjects will be summarized and analyzed ‘as treated’ i.e. by actual treatment group. [000236] PK analyses will be based on the PK analysis set defined as subjects that receive at least one dose of gimsilumab and have at least 1 evaluable post-dose pharmacokinetic sample. [000237] A summary of the number and percentage of subjects entering and completing each phase of the study by treatment group and overall for each analysis set (Analysis set: FAS). [000238] A by-subject listing of analysis set details including center, subject identifier, inclusion/exclusion flag for each analysis set and reason for exclusion from an analysis set. G. Demographic and Other Baseline Characteristics [000239] Demographic and other baseline characteristics will be summarized by treatment group and for both treatment groups combined (Total) using the ITT analysis set. The summaries provided will include the following: · Demographic variables: - Age (continuous and categorical (<65 years; ≥65years)), - Sex, - Race (American Indian or Alaska Native; Asian; Black or African American; Native, Hawaiian or Other Pacific Islander; White; Other; Multiple) - Ethnicity (Hispanic or Latino, Not Hispanic or Latino) - Baseline Height - Baseline Weight - Baseline Body Mass Index (BMI) · Baseline disease characteristics: - Randomization strata (Lung injury/mild ARDS; moderate severe/ARDS) - Ventilation status - Ventilation type - ICU status - Oxygenation status - Oxygenation type - SpO2, FiO2, PaO2, P/F ratio, S/F ratio - Baseline ferritin, CRP, d-dimer, cardiac troponin I, LDH - Baseline Lung Injury Score - Baseline NEWS Total Score - Baseline 7-point Ordinal Scale - Baseline SOFA Total Score - Baseline anti-GM-CSF autoantibody concentration (continuous and by categories of <5 µg/mL, ≥5 µg/mL) - Days since onset of symptoms H. Efficacy Evaluation [000240] The statistical analysis for this multi-center study (with centers quite different in terms of number of subjects per center) will use the pooled set of subjects across all centers. Center will not be used as a stratification factor or covariate in the statistical analysis models. [000241] The primary efficacy analysis will be adjusted by baseline clinical status (lung injury/mild ARDS vs moderate/severe ARDS). Baseline clinical status is a randomization factor and the status as reported from the randomization system will be used for all efficacy analyses. [000242] The treatment effect for the primary, key secondary efficacy endpoints, and the 7-point ordinary scale will be examined for the following subgroups: site; clinical status (lung injury/mild ARDS vs. moderate/severe ARDS); age (<65 years, ≥65 years); sex (Male, Female); body weight (by quartiles); race (White, African American, additional groups must represent at least 25% of the population if not, will group as ‘All Other’); ethnicity (Hispanic or Latino, Not Hispanic Latino); invasive ventilator use at baseline (yes, no); baseline invasive ventilator use or severe ARDS at baseline (yes, no); presence of anti-GM-CSF auto antibodies at Screening (<5 µg/mL, ≥5 µg/mL); 7-point ordinal scale status at baseline; received Day 8 study drug (yes, no); and prohibited medications use (yes, no). [000243] Prohibited medication use will be aligned to time period of endpoint being summarized as follows: - Prohibited medication from Day 1 – Day 43 (Mortality by Day 43) - Prohibited medication from Day 1 – Day 29 (Survival and no mechanical ventilation by Day 29, Mechanical ventilation-free days by Day 29) - Prohibited medication during the study (Time to hospital discharge, 7-point ordinal scale) [000244] Summaries of the primary, key secondary efficacy variables and the WHO 7-point ordinal scale by treatment group and subgroups will be produced. Homogeneity of the treatment effect across subgroups may be investigated using graphical and analytical methods. An appropriate summary of the treatment effect (e.g., risk difference, mean difference, hazard ratio) and 95% confidence intervals will be estimated within each subgroup using the methods described for the main analysis for each endpoint. A forest plot showing these estimates and 95% confidence interval within each subgroup and overall will be provided. [000245] Multiple imputation methods replace each missing primary efficacy endpoint value with a set of m=10 plausible values based on a model predicting values for a missing data point based on available data, i.e., assuming a Missing at Random (MAR) missingness mechanism. [000246] This set of values represents the uncertainty about the correct value to be imputed. These complete datasets (generated by SAS PROC MI) are then analyzed by relevant statistical procedure (e.g., SAS PROC FREQ, SAS PROC LOGISTIC, etc) generating parameter estimates and their standard errors, followed by combining those results from these analyses (by using SAS PROC MIANALYZE). [000247] Graphical displays, based on the “tipping-point” analysis introduced by Yan 2009 and not requiring the MAR assumption, will be used to visualize the results of a two- dimensional set of sensitivity analyses using different imputations for missing binary endpoint values (e.g., either “death by Day 43” or “alive at Day 43” for the primary efficacy endpoint) for comparison of the two study treatments. All possible combinations of imputations of missing binary endpoint values in the gimsilumab and placebo group will be evaluated by statistical method, with study treatment as the only factor. I. Safety Evaluation [000248] All safety summaries and analyses will be based upon the safety analysis set as defined in section H. Safety analyses summarized by study period will be analyzed separately for each of the following periods as defined in section D: - Overall - Treatment Period (Day 1 – Day 15) - Follow-up Period 1 (Day 16 – Day 43) - Follow-up Period 2 (Day 44 +) - Overall – Hospitalized (Day 1 through DoD) - Overall – After Discharge (DoD +) Note: only subjects who were on study in a given period will be included in the analysis for that period (e.g. if a subject withdraws from study or dies before Day 43 they will contribute to the denominator for summaries in the Overall, Treatment Period, and Follow-up Period 1 periods, but not in summaries of Follow-up Period 2). J. Other Analyses 1. Pharmacokinetics [000249] Serum gimsilumab concentrations will be summarized (including geometric mean, CV%, and 95% confidence interval for post-baseline timepoints) at Baseline (pre-dose), Day 8 (pre-dose) and DoD/ET using descriptive statistics for the PK population. A scatter plot of individual concentrations (overlaid) versus actual time of sampling (relative to Day 1 dose) will be provided (conditioned on subjects receiving Day 1 or Day 1 and Day 8 doses of study drug). Pharmacokinetic data analysis will not be performed until after database lock as it is potentially unblinding. Population PK analysis, if conducted, will be described in a separate analysis plan and report. 2. Immunogenicity [000250] Serum anti-drug antibody (ADA) data will be summarized by visit and treatment for the safety analysis set (note, this analysis is distinct from the anti-GM-CSF auto- antibody test at Screening). The following will be summarized: ADA positive at baseline, ADA negative post baseline, ADA positive post baseline (regardless of baseline; Immunogenicity rate), and ADA positive post baseline (but negative at baseline). Assessment of ADA incidence and Day 8 pre-dose serum gimsilumab concentration will be descriptively summarized by: ADA positive on any day and ADA positive on Day 15. 3. Biomarker [000251] Actual and change from baseline serum cytokines and safety biomarker SP- D results will be summarized by treatment at Baseline (pre-dose), Day 4, Day 8, and DoD/ET using descriptive statistics for the safety analysis set. Summary plots of actual and change from baseline serum cytokines will be provided, where time=0 will be: Study Day 1, and Day of onset of symptoms. By-subject listings of biomarker results will be provided. Biomarker data analysis will not be performed until after database lock as it is potentially unblinding. Additional exploratory analyses may be performed. EXAMPLE 5: EFFICACY AND SAFETY OF GIMSILUMAB FOR HYPERINFLAMMATORY COVID-19 [000252] A clinical study based on the design in Example 3 was carried out with 227 enrolled subjects for a period of 6 months. 225 patients received at least one dose of study drug, comprising the safety and mITT populations (Figure 21). 113 patients received gimsilumab, and 112 received placebo. Almost all (96.2%) screened patients were treated as screening, randomization, and treatment could occur on the same day. Death occurred in 63 (28.0%) patients, and 7 (3.1%) patients withdrew from the study. 25 (21.9%) gimsilumab- treated patients and 23 (20.4%) placebo-treated patients had completed the study through week 24 by the data cut-off. [000253] As shown in Table 7, demographics, baseline clinical characteristics, and mean laboratory values were generally similar across the gimsilumab and placebo groups in the overall population. No patient demonstrated evidence of undiagnosed autoimmune pulmonary alveolar proteinosis as evaluated by anti-GM-CSF autoantibody measurements at baseline. Table 7. Demographics, baseline clinical characteristics, and mean laboratory values of the study subjects

NEWS = National Early Warning Score. SOFA = Sequential Organ Failure Assessment. *Data represents status at the time of dosing. ^** An anti-GM-CSF autoantibody measurement >5 μg/mL is consistent with an early phenotype of pulmonary alveolar proteinosis. * ^** Measurements were derived from a central laboratory and may have differed from the local laboratory results used at study screening. [000254] Although clinical management recommendations were rapidly changing throughout the study, medication use was generally similar between treatment groups (Table 8). Approximately 10% less patients in the gimsilumab group received systemic corticosteroids, although dexamethasone use was balanced across groups. Eleven (9.7%) patients in the gimsilumab group and 10 (8.9%) patients in the placebo group received a prohibited medication due to rapid decline. Table 8. Medication use before and during the study. 89

*Started and stopped prior to first dose of study drug. [000255] The results of the primary and key secondary efficacy analyses are shown in Table 9. There was no significant difference between the gimsilumab and placebo groups on the rate of all-cause mortality at day 43 [difference = 0.05 versus placebo, 95% CI (-0.06, 0.17), p = 0.349]. The gimsilumab and placebo groups experienced a 28.3% and 23.2% day 43 mortality rate, respectively. The time-to-death analysis, which included all available data, did not demonstrate a significant difference between groups, and overall mortality rates were nearly equal [hazard ratio = 1.1, 95% CI (0.7, 1.8), log-rank p = 0.774] (Fig.22). ⁷⁴⁰⁸⁶ ₇₀₄₂ 91 [000256] There was no difference between the gimsilumab and placebo groups on any of the key secondary endpoints. The gimsilumab group experienced a day 29 ventilator- free survival rate of 70.8%, while the placebo group experienced a rate of 69.6% [difference = 0.02, 95% CI (-0.10, 0.14), p = 0.737]. The mean number of ventilator-free days by day 29 was 19.6 (SD 12.7) and 20.1 (SD 12.6) in the gimsilumab and placebo groups, respectively. Both groups had a median of 29.0 ventilator-free days by day 29 (p = 0.479), demonstrating that the majority of patients were not treated with mechanical ventilation during this study period. The gimsilumab group required a median of 13.0 days to hospital discharge, while the placebo group required 15.0 days [hazard ratio = 0.9, 95% CI (0.7, 1.3), log-rank p = 0.723]. [000257] Analyses of other endpoints, including laboratory markers, are shown in Table 10. There were generally no differences across treatment groups with respect to changes from baseline on any of these endpoints. Table 10. Other clinical and laboratory analyses of the mITT population

Patients who were discharged did not have measurements/assessments after discharge. Day of discharge included only patients who were discharged alive; assessments and samples could not be obtained from patients who were expiring. [000258] Most pre-specified subgroup analyses showed no differences between treatment groups on the primary and key secondary endpoints (Figure 23). [000259] Most AEs of interest that could have been related to gimsilumab’s mechanism of action, including hematopoietic disturbances, liver toxicity, and pulmonary alveolar proteinosis, were generally comparable across groups. As shown in Table 11, the gimsilumab group appeared to have a small elevation in SAEs classified under the infections MedDRA system organ class (SOC), although the placebo group had slightly higher rates of SAEs in the renal and cardiac SOCs. There were slightly less infusion-related reactions in the gimsilumab group (44.2%) relative to the placebo group (50.9%). Table 11. Summary of events observed in the safety population

AE = adverse event. SAE = serious adverse event. SOC = system organ class as defined by the Medical Dictionary for Regulatory Activities (MedDRA). *Includes only SAEs by MedDRA Preferred Term that appeared in >1 patient in either treatment arm. **Clinical diagnosis made separately from autoantibody measurements taken at baseline. [000260] Despite a higher rate of infections, respiratory, renal, vascular, and cardiac SAEs were lower in the gimsilumab group compared to the placebo group, suggesting systemic effects of gimsilumab (See Table 12). Gimsilumab-treated patients reported approximately 50% fewer renal and cardiac grade 3-5 treatment-emergent adverse events compared to the placebo group. Table 12. Serious Treatment-Emergent Adverse Events EXAMPLE 6: BENEFIT OF ANTI-GM-CSF THERAPY (GIMSILUMAB) FOR MECHANICALLY-VENTILATED COVID-19 PATIENTS [000261] Benefits of anti-GM-CSF therapy were demonstrated in a subpopulation of patients mechanically ventilated at baseline. Ventilated subjects reflected about 20% of the enrolled subjects. [000262] As shown in Table 13, subgroup of patients mechanically ventilated at baseline demonstrated evidence of benefit of treatment with gimsilumab over placebo, including: 1. 10% absolute reduction (22% relative reduction) in all-cause mortality at Day 43 in gimsilumab vs placebo group. P=0.2582*. 2. Nominally significant 35% absolute improvement (more that 2-fold increase) in ventilation-free survival at Day 29 in gimsilumab vs placebo group, p=0.0083*. 3. Improvement in mechanical ventilation-free days by Day 29, with gimsilumab- treated patients experiencing a median of 8.0 ventilation-free days vs 0.0 days for placebo-treated patients, p=0.0347*. 4. Improvement in median time to hospital discharge by Day 29, with a 2.5 times increased likelihood of discharge in the gimsilumab vs placebo group, p=0.05328.

^{740 T 86} ₇ ^a ₀ ^b ₄₂ ^{le 13. Subgroup analysis of patien} _{ts invasively ventilated at ba} 9 _s 8 _{eline (N} = ⁴ ₁₎ [000263] Laboratory assessments in the ventilated subgroup exhibited changes in key biomarkers associated with COVID-19 progression (e.g., CRP and eGFR) demonstrated marked improvements in gimsilumab-treated patients relative to placebo-treated patients (Fig. 24). EXAMPLE 7: RAPID, OPEN LABEL, PHASE 2, MULTI-ARM, MULTISTAGE TRIAL TO EVALUATION THE POTENTIAL EFFICACY OF NAMILUMAB IN HOSPITALIZED COVID-19 PATIENTS [000264] A rapid, open-label, phase 2, multi-arm, multi-stage trial to evaluate the potential efficacy of namilumab in hospitalized COVID-19 patients was conducted. The subjects included in the study were 16 years and older, hospitalized with confirmed SAR-CoV- 2 pneumonia, and having CRP levels equal to or over 40 mg/L. [000265] Subjects in the namilumab treatment arm received the usual care and a single dose of 150 mg namilumab IV infusion on Day 1. Primary outcome was CRP levels. Secondary outcomes included: 1. Time to improvement on WHO Clinical Progression Improvement Scale. 2. SpO2/FiO2. 3. Length of hospital stay. 4. Proportion of patients discharged at Day 28. 5. Hospital survival status at Day 28. 6. Respiratory rate, body temperature. 7. Lymphocyte and neutrophil counts, ferritin, D-Dimer, LDH. 8. AEs, SAEs, overall survival. [000266] The study results revealed that namilumab improved inflammatory markers in subjects with COVID-19. EXAMPLE 8: Randomized study of Gimsilumab or Namilumab in ventilated subjects with severe COVID-19 A. Arms and Study Treatment [000267] A study will be performed in ventilated subjects with severe COVID-19 to further validate the findings of Example 6. An individual will be eligible for inclusion in this study if all of the following criteria are met: 1. Age 18 years and older, inclusive. 2. Hospitalized. 3. Confirmed SARS-CoV-2 infection. 4. Clinical evidence of lung injury or ARDS. 5. CRP ≥ 1,000 ng/ml. 6. Intubated and mechanically ventilated. Table 15. Treatment Arms Arm Randomized Treatment B. Therapeutic Endpoints [000268] The primary endpoint of the study will be a decrease in the incidence of mortality and no mechanical ventilation at Day 29. Key secondary endpoints will include ventilation-free days, days to hospital discharge, and mortality.