Presentations at ECCMID Highlight New Data for DLA Agents
On July 19, 2021, ContraFect (NASDAQ:CFRX) announced multiple data presentations at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). A copy of the presentations can be accessed on the company’s website here. An overview of each the presentations is given below:
Synergistic anti-biofilm activity of exebacase and rifampin, vancomycin and daptomycin against Staphylococcus epidermidis strains responsible of bone and joint infections
This presentation included new data regarding the use of exebacase in treating bone and joint infections (BJI) with and without standard of care antibiotics. BJI and prosthetic joint infections (PJI) are increasing in prevalence as the population in Western countries continues to age. The economic burden of PJI was approximately $500 million in 2009 and that number is expected to continue to escalate (Kurtz et al., 2012). Staphylococcus aureus is the cause of anywhere from 30-70% of BJI, while Staphylococcus epidermidis is the most common pathogen in PJI.
For this study, 19 clinical isolates were tested for their susceptibility to oxacillin, rifampin, vancomycin, daptomycin, and exebacase alone along with combination treatments of exebacase with the various antibiotics. The following chart shows that all clinical isolates were susceptible to exebacase, most were susceptible to vancomycin and daptomycin, and most were resistant to oxacillin. Susceptibility is shown through a low minimum inhibitory concentration (MIC) value, which is the lowest concentration of an antimicrobial that will inhibit visible growth of a microorganism.
For these experiments, each isolate was allowed to grow a biofilm before treatment for 24 hours with exebacase alone, an antibiotic alone, or exebacase + an antibiotic with an outcome of the log reduction in bacterial growth and the % decrease in biomass. The following chart shows that compared to exebacase monotherapy there was a synergistic effect on bacterial growth when exebacase was combined with rifampin, vancomycin, or daptomycin with the maximum effect being a 3.5 log, 2.8 log, and 3.1 log decrease in bacterial growth, respectively.
Lastly, while the antibiotics alone did not appear to have much of an effect on biofilm formation, there was a synergistic effect between exebacase and the antibiotics tested with maximum decreases in biomass of 81-85%.
In summary, exebacase exhibits synergistic anti-microbial and anti-biofilm activity with a number of different antibiotic agents and could be useful as a therapy for BJI and PJI.
Lysin CF-370 exhibits potent bactericidal activity against clinical MDR and XDR Pseudomonas aeruginosa isolates including carbapenem- and/or colistin- resistant forms
CF-370 is the company’s lead engineered lysin development candidate targeting Gram-negative bacterial species. The following figure shows how lysins are effective against Gram-positive bacteria due to their ability to easily interact with the peptidoglycan layer. However, Gram-negative bacteria have an outer membrane that acts as a barrier against most lysins, thus preventing them from reaching the peptidoglycan layer. While the majority of purified Gram-negative lysins have no antimicrobial activity, there are a select few that have some activity in low ionic strength buffers (indicated by the asterisk in the following figure on the right). It is these lysins that ContraFect used as lead compounds to modify in order to increase their anti-microbial activity, with CF-370 emerging as the lead candidate from this research.
The following tables show that CF-370 has potent activity against Pseudomonas aeruginosa isolates, with the lower table showing that the compound is active against various clinical isolates that are resistant to a number of different antibiotics.
CF-370 exhibits synergism with a number of different antibiotic compounds. The following example shows that for P. aeruginosa isolate WC-452, which is resistant to both imipenem and meropenem, combination therapy of either of those compounds and CF-370 results in a MIC value of 0.125, showing that CF-370 can resensitize that isolate to treatment with compounds to which it had developed resistance.
The company also recently presented data showing that CF-370 not only has activity against P. aeruginosa, but also against a number of other Gram-negative pathogens, including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Enterobacteriaceae cloacae. The following table shows low MIC values for exebacase against most of the clinical isolates tested for each of the aforementioned species.
These results are very exciting as they allude to the fact that CF-370 could potentially be used to battle a wide range of Gram-negative infections, not just those caused by P. aeruginosa.
CF-296 Publications Highlight its Anti-Staphylococcus Activity
On July 19, 2021, ContraFect announced two recent peer-reviewed publications regarding the in vivo activity of CF-296, an engineered lysin with potent bactericidal and anti-biofilm activity against S. aureus.
Activity of Lysin CF-296 Alone and in Addition to Daptomycin in a Rat Model of Experimental Methicillin-Resistant Staphylococcus aureus Osteomyelitis
This manuscript described in vivo data from a study of CF-296 in a rat model of acute methicillin-resistant S. aureus (MRSA) osteomyelitis (Karau et al., 2021). The results of the study showed that CF-296 has potent anti-staphylococcal activity both as a monotherapy and in combination with daptomycin along with being well tolerated.
Efficacy assessment of lysin CF-296 in addition to daptomycin or vancomycin against Staphylococcus aureus in the murine thigh infection model
This manuscript described results from a study of CF-296 in a murine S. aureus infection model (Asempa et al., 2021). The results showed that CF-296 exhibited efficacy both as a monotherapy and when used in combination with both daptomycin and vancomycin. In addition, treatment with both CF-296 and either daptomycin or vancomycin resulted in significantly enhanced antibacterial activity relative to either of the antibiotics alone.
ContraFect continues to accumulate a wealth of data regarding its direct lytic agent (DLA) platform. We are very intrigued by the data showing CF-370 has activity against a wide range of Gram-negative species and we will be very interested to see what direction the company takes that compound following additional analysis and preclinical testing. In the meantime, we are expecting the results of an interim futility analysis from the Phase 3 trial of exebacase sometime in the second half of 2021. With no changes to our model our valuation remains at $23 per share.
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