CFRX: CF-370 Effective in Rabbit Lung Infection Model Caused by Klebsiella Pneumoniae…
NASDAQ:CFRX
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Business Update
Multiple Presentations Highlight Lysin Activity Against Gram-Negative Pathogens
On June 20, 2023, ContraFect Corp. (NASDAQ:CFRX) announced multiple presentations at ASM Microbe 2023 highlighting significant activity of multiple lysins against different Gram-negative pathogens.
Efficacy of lysin CF-370 in addition to amikacin or meropenem in a neutropenic rabbit lung infection model caused by Klebsiella pneumoniae (Pulse et al., 2023).
This study examined the efficacy of CF-370 alone and in combination with amikacin or meropenem in a neutropenic rabbit pneumonia model infected with either drug-sensitive or drug-resistant Klebsiella pneumoniae. Following inoculation with K. pneumoniae, CF-370 was administered IV as a single dose or every 24 hours, amikacin was delivered intravenously every 8 hours, and meropenem was dosed subcutaneously every 8 hours. Animals were euthanized after 91 hours. The following figures show the mean log reduction in bacterial load following treatment with amikacin (left figure) or meropenem (right figure). CF-370 enhanced the in vivo efficacy of both antibiotics against both drug-sensitive and drug-resistant K. pneumonia strains.
PK-PD relationships and PK drivers of efficacy of the novel antibacterial lysin CF-370 in a rabbit pneumonia model caused by a carbapenem-resistant Pseudomonas aeruginosa (Lehoux et al., 2023).
This study examined the relationship between CF-370 and efficacy in a rabbit pneumonia model caused by carbapenem-resistant Pseudomonas aeruginosa PA20. Treatment began six hours after rabbits were inoculated with P. aeruginosa and continued for 24 hours. CF-370 was administered separately as a single dose, two doses spaced over 12 hours, or 3 doses spaced by 8 hours. Tissue samples were collected 24 hours after the last dose of meropenem. The following image shows the efficacy of CF-370 at different dosing fractions with and without meropenem. CF-370 in combination with meropenem results in a statistically significant reduction in lung infection when compared to meropenem alone or CF-370 alone, which agrees with previous results.
In addition to efficacy, this study also examined the target systemic CF-370 exposure that would result in bacterial clearance in the lung. The following table shows that an AUC/MIC of 12 or greater results in a >3-log drop in bacterial load and could be predictive of efficacy in the clinic.
Engineered lysins with potent in vitro activity against Burkholderia spp. and Yersinia pestis (Vila-Farres et al., 2023).
This study was undertaken to design lysins that have antimicrobial activity against Yersinia pestis (CDC Category A bioterrorism agent) and Burkholderia species (spp) (CDC Category B bioterrorism agent). Over 200 compounds were tested against Y. pestis and eight lead lysins were selected based on low minimum inhibitory concentration (MIC) values compared to non-engineered controls. Over 300 compounds were tested against five Burkholderia spp and 10 lead lysins were likewise selected. Three of the lead compounds were active against both Y. pestis and Burkholderia spp. Time-kill assays showed significant bactericidal activity (reductions >3-log10 CFU/mL) and there was no hemolysis of red blood cells observed with any of the lead compounds (highest concentration tested was 128 µg/mL). Additional analyses will be used to select three lead compounds for animal efficacy studies.
Efficacy of single and daily dose of lysin CF-296 in addition to daptomycin in a rat methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model (Karau et al., 2023).
This study was designed to test the efficacy of a single vs daily doses of CF-296 (an engineered antistaphylococcal lysin) with and without daptomycin (DAP) in a rat MRSA osteomyelitis model. Osteomyelitis was established by injecting arachidonic acid and MRSA into the knee joint. After one week, rats were assigned to one of five groups: no treatment, DAP twice daily, CF-296 once daily, CF-296 once daily with DAP, CF-296 single dose on day 1 of treatment, CF-296 single dose on day 1 in addition to DAP. The following graph shows that all treatment groups had less MRSA recovered than untreated animals (P<0.0022). The greatest reduction in MRSA was seen with daily doses of CF-296 in addition to DAP, thus this treatment regimen may be a potential therapy for treating osteomyelitis.
Conclusion
The results presented at ASM Microbe show how ContraFect’s lysin platform continues to show promise against a wide-ranging group of pathogens, including the ability to generate lead development compounds with potent activity against two difficult to treat species, Burkholderia and Yersinia. We continue to anticipate an IND filing for CF-370 later this year and the continued enrollment of patients into the Phase 1b/2 trial of exebacase for the treatment of prosthetic joint infections. With no changes to our model our valuation remains at $7.00 per share.
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