1342. Comparison of Lysin CF-301 (Exebacase) Activity Against S. aureus Isolates from Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102) to Contemporary Surveillance Isolates
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Background: CF-301 (exebacase) is a novel, recombinantly-produced, bacteriophage-derived lysin (cell wall hydrolase) which is the first lysin to enter Phase 2 (Ph2) in the United States (US) and is being studied for the treatment of S. aureus bacteremia including endocarditis. We examined the activity of CF-301 against methicillin sensitive and methicillin resistant S. aureus (MSSA and MRSA) isolates from participants in the ongoing, CF-301 ‘first in-patient’ Ph2 study (NCT03163446) in comparison to activity reported in a recent surveillance study.

Methods: Patients with complicated bacteremia or endocarditis caused by S. aureus were enrolled into Study CF-301-102 at study centers in the US and Guatemala between 2017 and 2018. Baseline isolates from blood cultures were collected prior to administration of CF-301. The activity of CF-301 activity against the first 36 isolates of MRSA (14) and MSSA (22) was determined at a central laboratory. Surveillance data for CF-301 was generated against 300 isolates of MRSA (150) and MSSA (150) collected between 2016 and 2017 from patients with various infection types at US centers. CF-301 MICs were determined using the modified broth microdilution method approved by the CLSI for CF-301.

Results:

In vitro activity of CF-301 against S. aureus isolates from Ph2 Study CF-301-102 and surveillance

Organism

Source

N

MIC (µg/mL)

0.125

0.25

0.5

1

2

MIC50

MIC90

MSSA

Ph2

22

1

6

13

2

0.5

0.5

Surveillance

150

2

91

57

0.5

1

MRSA

Ph2

14

3

10

1

0.5

0.5

Surveillance

150

5

108

37

0.5

1

The CF-301 MICs of baseline patient isolates from the Ph2 study ranged from 0.125 – 1 µg/mL. CF-301 MIC50/90 values for all MSSA and MRSA isolates were 0.5 µg/ml. CF-301 MICs reported in a recent the surveillance study ranged from 0.25-1 µg/mL, with MIC50/90 values of 0.5/1 µg/mL.

Conclusion: The activity of CF-301 against baseline S. aureus isolates from blood cultures obtained from bacteremic patients enrolled in the Ph2 study was similar to that observed in the surveillance study. Based on data from previously presented exposure target attainment animal studies, PK/PD modeling and preliminary non-clinical breakpoint assessments, we expect that strains with MIC values of ≤1 µg/mL will be susceptible to the clinical CF-301 dose (0.25mg/kg) under study in Ph2.

Diane Anastasiou, MT (ASCP)1, Alena Jandourek, M.D.2, Maria Traczewski, BS3, Cara Cassino, M.D.2 and Raymond Schuch, Ph.D.2, (1)ContraFect Corporation, Yonkers, NY, (2)ContraFect Corp, Yonkers, NY, (3)Clinical Microbiology Institute, Wilsonville, OR

Disclosures:

D. Anastasiou, ContraFect Corporation: Consultant , Consulting fee .

A. Jandourek, ContraFect Corporation: Employee , Salary .

M. Traczewski, None

C. Cassino, ContraFect Corporation: Employee , Salary .

R. Schuch, ContraFect Corporation: Employee , Salary .

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