Study of Safety and Efficacy of ALT-100mAb in Participants With Moderate/Severe ARDS

Inclusion Criteria:

To be eligible for this study, a participant must meet all of the following criteria:

1. Hospitalized (or documentation of a plan to admit to the hospital if the patient isin an emergency department) male or non-pregnant female 18 years and above of age attime of enrollment.

2. Participant (or LAR) is able and willing to provide written informed consent, whichincludes compliance with study requirements and restrictions listed in the consentform.

3. Participant has a diagnosis of moderate or severe ARDS: A participant with a diagnosis of moderate or severe ARDS according to the Berlindefinition of ARDS:

4. Acute onset of respiratory failure within 1 week of a known clinical insult ornew or worsening respiratory symptoms.

5. Respiratory failure associated with known ARDS risk factors and not fullyexplained by either cardiac failure or fluid overload (an objective assessmentof cardiac failure or fluid overload is needed if no risk factors for ARDS arepresent).

6. Radiological abnormalities on chest x-ray or computed tomography (CT) scan, ie,bilateral opacities that are not fully explained by effusions, nodules, masses,or lobar/lung collapse.

7. Hypoxemia: i. Moderate ARDS: PaO2/FiO2 more than 100 mmHg (more than 13.3 kPa) to 200 mmHg andbelow (26.6 kPa and below) with PEEP 5 cmH2O and above, or imputed SpO2/FiO2equivalent. ii. Severe ARDS: PaO2/FiO2 100 mmHg and below (13.3 kPa and below) with PEEP 5 cmH2Oand above. OR Participant presents with acute respiratory failure phenotypically similar toARDS in a setting demonstrating clinical risk for ARDS, whether or not they meet theBerlin criteria, and requiring heated and humidified HFNC 30 L/min and above and 100percent FiO2, or NIPPV (ie, BiPAP/CPAP) for hypoxemia. OR Participant presents with acute respiratory failure phenotypically similar toARDS in a setting demonstrating clinical risk for ARDS, do not meet the Berlincriteria, and initially treated with 12 continuous hours and above with HFNO usinggas flow of 40 L/min and above or treated with non-invasive ventilation (NIV), andhas a PEEP of 5 cm and above H2O and PaO2/FIO2 below 300 mm Hg.

8. Administration of study treatment must be planned to occur within 12 hours of theparticipant's moderate or severe ARDS diagnosis and within 4 hours of initiation ofMV (in the case of individuals requiring immediate MV).

9. Females must be non-pregnant and non-lactating, and either surgically sterile (eg,tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), oruse highly effective contraceptive method (oral contraceptive pills [OCPs],long-acting implantable hormones, injectable hormones, a vaginal ring or anintrauterine device [IUD]) from screening until study completion or bepost-menopausal for 12 months and above. Post-menopausal status will be confirmedthrough testing of follicle-stimulating hormone (FSH) levels at screening foramenorrheic female participants, but the result is not required prior to enrollment.Female participants whose only partner has had a vasectomy, and female participantswho are abstinent from heterosexual intercourse as part of their usual lifestylewill also be eligible for participation.

10. Women of child-bearing potential (WOCBP) must have a negative pregnancy test atscreening and admission and be willing to have additional pregnancy tests asrequired throughout the study.

11. Males must be surgically sterile (more than 30 days since vasectomy with no viablesperm), abstinent, or if engaged in sexual relations with a WOCBP his partner mustbe surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy,bilateral oophorectomy) or using an acceptable, highly effective contraceptivemethod from screening until study completion, including the Follow-up Period.Acceptable methods of contraception include the use of condoms and the use of aneffective contraceptive for the female partner (WOCBP) that includes: OCPs,long-acting implantable hormones, injectable hormones, a vaginal ring, or an IUD.Male participants whose female partner is post-menopausal, and participants who areabstinent from heterosexual intercourse as part of their usual lifestyle will alsobe eligible.

12. Male participants must agree to refrain from donating sperm from screening untilstudy completion, including the Follow-up Period, for at least 60 days after thelast dose of study treatment.

13. Participant is willing and able to undergo all study procedures and attend thescheduled follow-up visit/s per protocol.

Exclusion Criteria:

A participant who meets any of the following criteria must be excluded from the study:

1. Participants with ARDS consequent to COVID-19 infection.

2. Participants requiring immediate MV who have been intubated and on MV for more than 4 hours prior to the planned administration of study treatment on Day 1

3. Moribund participant not expected to survive more 24 hours, in the opinion of theInvestigator.

4. Use of extracorporeal life support (eg, ECMO) or, in the opinion of theInvestigator, there is a high likelihood that extracorporeal life support will beinitiated within 48 hours after randomization.

5. Participant has an underlying clinical condition where, in the opinion of theInvestigator, it would be unlikely that the participant would be able to come offventilation, eg, chronic progressive neuromuscular or respiratory disease.

6. Severe chronic respiratory disease (eg, known chronic obstructive pulmonary disease [COPD], pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF],interstitial lung disease [ILD]) requiring supplemental oxygen therapy or MVpre-hospitalization (eg, prior to ARDS diagnosis).

7. Evidence of life-threatening dysrhythmia (eg, ventricular tachycardia, ventricularfibrillation) or cardiac arrest on presentation.

8. Evidence of new or preexisting decompensated heart failure.

9. Absolute neutrophil count lesser than1000 per mm3.

10. Platelet count less than 50000 per mm3.

11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 5 ×ULN.

12. Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (based onMDRD equation) or requiring hemofiltration or dialysis.

13. Known or suspected active and untreated tuberculosis (TB), HIV, hepatitis B or Cinfection. Note: Results of TB, hepatitis B and C, and HIV tests are not required prior toenrollment if there is no suspicion of active infection.

14. Known history of severe allergic, anaphylactic, or other hypersensitivity reactionsto chimeric, human, or humanized antibodies, fusion proteins, ALT-100 excipients, ora history of drug or other allergy including severe allergic reaction that in theopinion of the Investigator or MM, contraindicates participant participation.

15. Use of any immunomodulatory biologic (eg, anti-IL-1, anti-IL-6R, anti-TNF,inhibitors of complement signaling), cell therapies (eg, mesenchymal stem cells), orsmall molecule Janus kinase (JAK) inhibitors within the past 7 days or within 5half-lives (whichever is longer), or planned use of any of these agents fromscreening until Day 60 of the study, unless approved by the MM. The following willbe allowed/ disallowed as indicated:

16. Immunomodulatory biologics for treatment of COVID-19 are excluded and shouldnot be used until Day 60 unless discussed with the MM. Other non-biologicimmunomodulators (non-JAK inhibitors), eg, medicines for previoustransplantation, or DMARDS, if on a stable dose for 8 weeks and above arepermitted.

17. Ongoing chronic (4 weeks and above) use of corticosteroids more than 10 mg/dayof prednisone or equivalent at the time of randomization is prohibited. Acorticosteroid dose that has been tapered to 10 mg or less within 14 days ofrandomization is also prohibited.

18. Participants who have circulatory shock requiring vasopressors at randomization orwithin 24 hours prior to randomization will be excluded from study participation. Participants who present at screening with ARDS and septic shock may be enrolled ifthe participant is on one vasopressor or, if on 2 vasopressors, if the Levofed (norepinephrine) dose is 1 microgram/kg/min and lesser. Participants with ARDS and septic shock who are on 3 and above vasopressors ie,Vasopressin, Levofed (norepinephrine), Neosynephrine (phenelephreine), at screeningare excluded from study participation. Participants with ARDS and septic shock who are on 2 vasopressors where the Levofeddose is more than 1 micro gram/kg/min are excluded from study participation.

19. Participation in a clinical research study evaluating another IP or therapy within 3months and less than 5 half-lives of the IP prior to the Screening Visit.

20. Any physical examination findings, and/or history of any other illness, concomitantmedications, or recent live vaccines that, in the opinion of the Investigator, mightconfound the results of the study or pose an additional risk to the participant bytheir participation in the study.

21. Administered a live vaccine within 14 days prior to IP administration and throughoutthe duration of the study.