PK of BV100 in Patients VABP Suspected or Confirmed to Be Due to CRAB

Inclusion Criteria:

Patients who meet all the following diagnostic and clinical criteria are eligible for the study:

1. Provide written informed consent prior to any study related procedures not part ofnormal medical care. Surrogate consent/use of a legally authorized representativemay be provided, if permitted by local country and institution specific guidelines.If a patient regains consciousness while in the study and, per the Investigator'sjudgment, the patient is able to read, assess, understand, and make his/her owndecision to participate in the trial, the patient can agree to continueparticipation and the patient should be re consented, if required by local countryand institution specific guidelines.

2. Male or female patients ≥ and < 80 years of age at the time of Informed Consent Form (ICF) signing with a body mass index (BMI) of < 40 kg/m2 at the time of ICF signing.

3. Hospitalized for ≥ 48 hours, intubated (via endo or nasotracheal tube, includingtracheostomy patients) and receiving mechanical ventilation for ≥ 48 hours at thetime of randomization, and with acute changes made in the ventilator support systemto enhance oxygenation, as determined by arterial blood gas, or worsening PaO2/FiO2ratio.

4. All patients must have a chest radiograph or a lung CT scan within 48 hours prior torandomization showing the presence of new or progressive infiltrate(s) suggestive ofbacterial pneumonia (based on Investigator's evaluation).

5. Clinical findings to support diagnosis of VABP. At least 1 of the following must bedocumented to be present within 24 hours prior to randomization:

• Documented fever (oral ≥ 38.0 °C [100.4 °F] or a tympanic, temporal, rectal, orcore temperature ≥ 38.3 °C [101.0 °F], axillary or forehead scanner ≥ 37.5 °C [99.5 °F]) OR

• Hypothermia (rectal/core body temperature ≤ 35.0 °C [95.2 °F]), OR

• Leukocytosis with total peripheral white blood cell count (WBC) ≥ 10 000cells/mm3, OR

• Leukopenia with total peripheral WBC count ≤ 4500 cells/mm3.

6. Acute Physiology and Chronic Health Evaluation (APACHE II) score between 8 and 30,inclusive, within 24 hours prior to randomization. Any data collected before ICFsignature as part of a routine standard for patient care (e.g., laboratory values,Glasgow Coma Score, Acute Physiology Score [APS]) can be used for Screening Visitassessment, if applicable, without repeating the assessments.

7. High probability of pneumonia due to A. baumannii, defined as follows:

• RDT, performed within 36 hours prior to randomization, using an acceptablerespiratory sample (PBS, BAL, mini BAL, or ETA) positive for A. baumannii, OR

• A surveillance culture from a respiratory sample positive for A. baumanniiwithin 72 hours prior to randomization.

Part B specific:

1. Patients who have been treated previously with an empiric antibiotic regimen andhave failed treatment, both clinically and microbiologically, if they have anidentified CRAB which has been shown to be non-susceptible in vitro to each of theantibiotic(s) of the empiric antibiotic regimen or has been identified from aculture performed after at least 48 hours of empiric antibiotic regimen, AND/OR

2. Has an infection caused by A. baumannii organisms known to be resistant to colistin (defined as MIC ≥ 4 mg/L by a non-agar-based method) based on evidence from cultureor susceptibility testing after at least 48 hours of antibiotic treatment.

Exclusion Criteria:

• Patients who meet any of the following criteria are not eligible to participate inthis study:

1. Known or suspected community acquired bacterial pneumonia or viral, fungal, orparasitic pneumonia.

2. Sustained shock with persisting hypotension requiring vasopressors to maintainmean arterial pressure ≥ 60 mmHg

3. Known or suspected allergy to polymyxin, rifabutin, BAT, or their excipients.

4. Any of the following health conditions:

• Confirmed legionella infection (Legionella pneumophila pneumonia),Aspergillus spp. pneumonia (testing is not required)
• Candida spp. infection requiring systemic treatment
• Cystic fibrosis
• Known or suspected Pneumocystitis jiroveci pneumonia
• Known or suspected active tuberculosis
• Lung abscess
• Solid organ transplant within 6 months prior to randomization
• Pleural empyema
• Evidence of deep seated infection outside the respiratory tract, e.g.,endocarditis, osteomyelitis.
• Known or suspected neuropathy or neuromuscular disease
• Known HIV infection

5. Bronchial obstruction or a history of post obstructive pneumonia (this does notexclude patients with pneumonia who have an underlying chronic obstructivepulmonary disease).

6. Acute graft versus host disease Grade ≥ 3.

7. Expected survival < 72 hours or a Do Not Resuscitate Order.

8. Burns > 40% of total body surface area.

9. Current or anticipated neutropenia with absolute neutrophil count < 1000cells/mm3.

10. Severe renal disease defined as an estimated creatinine clearance as perCockcroft Gault (CLCR CG) < 30 mL/minute or estimated glomerular infiltrationrate (eGFR) as per Modified Diet in Renal Disease (MDRD) equation < 30mL/min/1.73 m2, or requirement for peritoneal dialysis, hemodialysis,hemofiltration, or a urine output < 20 mL/hour over a 24 hour period.

11. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalinephosphatase (ALP), or bilirubin (conjugated/unconjugated) ≥ 3 × upper limit ofnormal (ULN) values used by the laboratory performing the test or Child PughClass B and C in patients with chronic liver function impairment. Evidence ofsignificant hepatic disease or dysfunction, including known acute viralhepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepaticencephalopathy.

12. Received systemic or inhaled antibiotic therapy potentially effective againstA. baumannii within 72 hours prior to randomization for ≥ 36 hours

13. Investigator's opinion of clinically significant electrocardiogram (ECG)finding such as new ischemic changes, infarct, or ventricular arrhythmia withimmediate potential for a fatal outcome, bradycardia not corrected by pacemakeror medication, or, prior to the current infection, a history of New York HeartAssociation (NYHA) Class IV cardiac failure defined as severe limitations -experiences symptoms even while at rest, mostly bedbound patients, within 1year.

14. Abnormal QT interval corrected by Fridericia (QTcF): > 450 ms confirmed withrepeat ECG.

15. Stroke (ischemic or intracerebral hemorrhage) within 5 days prior torandomization.

16. Women who are pregnant or nursing, or who are of childbearing potential andunwilling to use an acceptable method of birth control (e.g., intra-uterinedevice [IUD], male partner sterilization, or complete sexual abstinence) for atleast 30 days after the last dose of the study drug. Negative pregnancy testshould be obtained before randomization. The following women are not consideredto have childbearing potential: 1) those who have undergone surgicalsterilization, including hysterectomy and/or bilateral oophorectomy and/orbilateral salpingectomy, but excluding bilateral tubal occlusion; 2) age ≥ 50and post-menopausal as defined by amenorrhea for 12 months or more followingcessation of all exogenous hormonal treatments.

17. Male patients with female partners of childbearing potential who are unwillingto use 2 methods of contraception, one of which must be a barrier method (e.g.,condom), for at least 30 days after the last dose of study drug.

18. Previous exposure to BV100.

19. Patients who are currently enrolled in or have not yet completed at least 30days since ending another investigational device or drug trial or are receivingother investigational agents.

20. Not willing to comply with all study procedures.

21. Confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on local standard-of-care assessments availableduring Screening, unless the suspected A. baumannii pneumonia is diagnosed 14days or more after the detection of SARS CoV 2.