Evaluating the Plasma, Epithelial Lining, and Alveolar Macrophage Concentrations of Intravenous Carbavance™ (RPX2014/RPX7009) in Healthy Adult Subjects

The worldwide spread of resistance to antibiotics among Gram-negative bacteria, particularly
members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of
hospital acquired infections. In particular, the recent dissemination of a serine
carbapenemase (e.g., KPC) in Enterobacteriaceae in US hospitals now poses a considerable
threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

Rempex is developing a fixed combination antibiotic of a carbapenem (RPX2014) plus a new
beta-lactamase inhibitor (RPX7009) which has activity against serine beta-lactamases,
including KPC. This Phase 1 study will assess the pharmacokinetics of intravenous RPX2014 and
RPX7009 in plasma and epithelial fluid.

Inclusion Criteria:

1. Healthy adult males and/or females, 18 to 55 years of age (inclusive) at the time of
screening.

2. Body mass index (BMI) ≥ 18.5 and ≤ 30 (kg/m2) and weight between 55.0 and 100.0 kg
(inclusive) at the time of screening.

3. Medically healthy with clinically insignificant screening results (e.g., laboratory
profiles, medical histories, electrocardiograms (ECGs), physical examination) as
deemed by the PI.

4. Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day
1.

5. Voluntarily consent to participate in the study.

Exclusion Criteria:

1. History or presence of significant oncologic, cardiovascular, pulmonary, hepatic,
renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic,
neurological, or psychiatric disease.

2. Positive urine drug/alcohol testing at screening (or Day -1).

3. Positive testing for human immunodeficiency virus (HIV) or hepatitis B surface antigen
(HBsAg).

4. History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.

5. Hypersensitivity or idiosyncratic reaction to beta-lactam antibiotics (e.g.
penicillins, cephalosporins, carbapenems, etc.).

6. Clinically significant pulmonary or any other disease that prevents a subject from
undergoing bronchoscopy with bronchopulmonary lavage.

7. History of seizures (e.g., epilepsy), head injury or meningitis requiring ongoing
anti-seizure medications.

8. Use of any prescription medication (with the exception of hormonal contraceptives or
hormone replacement therapy for females) within 14 days prior to Day 1.

9. Participation in another investigational clinical trial within 30 days prior to Day 1.

10. Females who are pregnant or lactating.

11. Surgery within the past three months prior to Day 1 determined by the PI to be
clinically relevant.

12. Any acute illness including clinically significant infection within 30 days prior to
Day 1.

13. QTcF interval >450 msec, or history of prolonged QT syndrome at screening (or Day 1).

14. Calculated creatinine clearance less than 80 mL/min (Cockroft-Gault method) at
screening.

15. Subjects who have any clinically significant abnormalities on laboratory values at
screening (or Day -1), including:

1. White blood cell count (WBC) < 3,000/mm3, hemoglobin < 11g/dL.

2. Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3.

16. Liver function abnormalities at screening (or Day -1) (defined by an elevation in
bilirubin, AST or ALT 1.5 x ULN of the normal range for subjects based on age and
sex).