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CFRX: Enrollment for Phase 2 Trial of CF-301 Complete; Data in 4Q18…

09/24/2018
By David Bautz, PhD

NASDAQ:CFRX

READ THE FULL CFRX RESEARCH REPORT

Business Update

Phase 2 Trial of CF-301 Fully Enrolled

On September 6, 2018, ContraFect Corp. (NASDAQ:CFRX) announced that the Phase 2 trial of CF-301 (exebacase) is fully enrolled. CF-301 is the company’s lead lysin product candidate being tested for the treatment of bacteremia, including those with endocarditis, caused by both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains of Staphylococcus aureus. The trial is an international, multicenter, randomized, double blind, placebo controlled study with a superiority comparison between CF-301 or placebo combined with the standard of care antibiotics. The study was expected to enroll approximately 115 patients randomized 3:2 to receive a single dose of 0.25 mg/kg CF-301 administered via a two-hour infusion or placebo along with standard of care antibiotics. The primary endpoint of the study will be early clinical response. Safety, tolerability, and pharmacokinetics will also be examined along with additional exploratory clinical and health economic endpoints. We anticipate topline results in the fourth quarter of 2018.

CF-301 Resensitizes Antibiotic Resistant Species

In September 2018, ContraFect presented new data for CF-301 at the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) / American Society for Microbiology (ASM) Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. The data showed that CF-301 is able to resensitize antibiotic resistant strains to be susceptible to the antibiotic to which they had developed resistance. The following table shows data from a checkerboard assay that shows the potency of CF-301 with different antibiotics (oxacillin, OXA; nafcillin, NAF; cefazolin, CFZ) along with their individual activities against nine MRSA strains. The minimum inhibitory concentration (MIC) is shown for each individual component (MICinitial) and in combination (MICfinal). MIC values ≤ 2.0 denote sensitivity while values ≥ 4.0 denote resistance. Fractional inhibitory concentration index (FICI) values ≤ 0.5 denote synergy. All combinations of CF-301 and the tested β-lactam antibiotics showed synergy.


View Exhibit I

A 21-day in vitro serial passage assay was performed to determine the effect of CF-301 treatment on OXA MIC values in MRSA strain MW2. Previously, the company presented data showing that as the MIC value for CF-301 increased (not by any more than 2-fold) the MIC value for OXA decreased. This data was recapitulated in this study as shown below.


View Exhibit II

The isolates denoted by the purple boxes above were subjected to sequencing analysis to determine specific mutations that may be responsible for the increased susceptibility to OXA. The following table shows that three different mutations were identified in the murA, lyrA, and oatA genes, and these mutations were confirmed as causative through a two-step allelic exchange process.


View Exhibit III

The in vitro effects seen in the serial passage assay were recapitulated in an in vivo rabbit infective endocarditis model, where treatment with CF-301 resulted in up to 16-fold reductions in MIC values for OXA, as shown in the following table. The MIC for OXA against MW2 (the strain used in the assay) is 32 μg/mL.


View Exhibit IV

Two of the mutants that exhibited 32-fold decreases in OXA MIC were sequenced to identify mutations that may be responsible for the change in activity. The following table shows four mutations that were identified that may be responsible for the decrease in OXA MIC among the mutants. In addition, both mutants had a loss of SCCmec, a mobile genetic element that can be transferred within the genome and between species, however the actual mutation(s) have yet to be identified.


View Exhibit V

The key takeaway from the preceding data presented by ContraFect is that CF-301 (and potentially lysins as a group) are able to resensitize antibiotic resistant bacteria to the antibiotic to which they developed resistance. This could be a huge advancement in the battle against antibiotic resistant bacteria and potentially increase the value of the lysin technology. In addition, this could be applicable to the clinic in that CF-301 may make antibiotic resistant infections more amenable to conventional antibiotic treatment when used as a co-therapy.

Conclusion

We’re glad to see that the Phase 2 trial is fully enrolled and we are excited to see the results in the fourth quarter of 2018. The in vitro and in vivo data that ContraFect has presented at various conferences over the past couple of years has given us confidence that the Phase 2 trial will be a success. Our valuation currently stands at $6 and we believe investors would be well served to take a closer look at the company in the lead up to the Phase 2 data release.

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