CF-370 / ContraFect - LARVOL DELTA

The Engineered Lysin, CF-370, is Active Against Antibiotic-Resistant Gram-Negative Pathogens In vitro and Synergizes with Meropenem in Experimental Pseudomonas aeruginosa Pneumonia. (PubMed, J Infect Dis) - "CF-370 is the first engineered lysin described with potent broad spectrum in vitro activity against multiple clinically-relevant Gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multi-system infection."

Gram negative • Journal • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

Lysin CF-370 exhibits potent antibacterial activity against multidrug-resistant strains and persisters of Pseudomonas aeruginosa and other gram-negative pathogens (NACFC 2023) - "Planktonic persister cells were isolated from stationary phase cultures and tested for susceptibility to CF-370 and comparator antibiotics, ciprofloxacin (inactive vs. persisters) and colistin (variably active vs. persisters), as previously described [1, 2]. Lysin CF-370 is active against a range of gram-negative pathogens, including those associated with airway infections in CF. There was no cross-resistance with antibiotics, and CF-370 was active against persister forms of all pathogens tested. These findings suggest that CF-370 may have the potential to address the unmet need for treatments for pulmonary exacerbations of CF caused by MDR gram-negative pathogens."

Gram negative • Infectious Disease • Pneumonia

Efficacy of Lysin CF-370 in Addition to Amikacin or Meropenem in a Neutropenic Rabbit Lung Infection Model Caused by Klebsiella pneumoniae (ASM Microbe 2023) - "Neutropenia was induced in New Zealand White rabbits by injecting cytoxan IP at 100 mg/kg on Day -4 and -1 relative to infection. CF-370 demonstrates additional benefit in vivo to AMK and MERO against K. pneumoniae, a clinically important cause of HAP / CAP infections. This is consistent with in vitro data showing that CF-370 synergizes with standard of care antibiotics used against resistant Gram-negative bacteria. Clinical evaluation of the administration of CF-370 in addition to SOCA to achieve maximum efficacy against sensitive and resistant (XDR) K. pneumoniae is warranted."

Clinical • Preclinical • Hematological Disorders • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases

PK-PD Relationships and PK Drivers of Efficacy of the Novel Antibacterial Lysin CF-370 in a Rabbit Pneumonia Model Caused by Carbapenem-Resistant Pseudomonas aeruginosa (ASM Microbe 2023) - " A dose-fractionation study was conducted in a rabbit pneumonia model caused by PA20 (CF-370 MIC =2 µg/mL, meropenem MIC = 16 µg/mL). CF-370 + MEM had a significant benefit in reducing lung P. aeruginosa bioburdens (vs either agent alone) in a rabbit pneumonia model. These results support previous efficacy data of CF-370 + MEM or amikacin in the same rabbit pneumonia model. In addition to MEM, a CF-370 AUC/MIC ratio of 12.2 is an appropriate PK target associated with significant lung bioburden reductions in the experimental rabbit model of pneumonia."

Clinical • PK/PD data • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

ContraFect Data Presentations at the 33rd Annual ECCMID Meeting Highlight the Potential Efficacy of Lysin CF-370 Against Antibiotic Resistant Gram-negative Pathogens (GlobeNewswire) - "ContraFect Corporation...announces today presentation data showing CF-370 is highly efficacious in a neutropenic rabbit pneumonia model against an extensively-drug-resistant (XDR) strain of Pseudomonas aeruginosa (P. aeruginosa).These data were recently presented at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) Annual Meeting held from April 15-18, 2023 in Copenhagen, Denmark....Lysin exebacase exerts potent in vitro bactericidal activity against Staphylococcus aureus strains associated with pulmonary exacerbations (PExs) of cystic fibrosis (CF)."

Preclinical • Cystic Fibrosis • Infectious Disease

ContraFect Announces Multiple Presentations of New Data at the 33rd Annual ECCMID Meeting (GlobeNewswire) - "ContraFect Corporation...announces today that the Company has been selected for an oral presentation and three poster presentations at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) Annual Meeting to be held from April 15-18, 2023 in Copenhagen, Denmark. The data being presented will feature both exebacase and CF-370, the Company’s lead product candidates with CF-370 demonstrating potent in vitro bactericidal activity against drug-resistant pathogens, including multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains."

Preclinical • Cystic Fibrosis • Genetic Disorders • Infectious Disease

Activity of lysin CF-370 at the cell envelope of Gram-negative (GN) ESKAPE pathogens revealed by electron microscopy (ECCMID 2023) - No abstract available

Gram negative • Infectious Disease

Bacteriolytic and anti-virulence activities of engineered lysin CF-370 against Gram-negative (GN) ESKAPE pathogens (ECCMID 2023) - No abstract available

Gram negative • Infectious Disease

Efficacy of lysin CF-370 in addition to amikacin in a neutropenic rabbit lung infection model caused by an extensively drug-resistant (XDR) P. aeruginosa (ECCMID 2023) - No abstract available

Clinical • Preclinical • Infectious Disease • Respiratory Diseases

ContraFect Reports Third Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "In addition, we completed the GLP toxicology studies of CF-370...and expect to submit an IND for CF-370 by the end of the first quarter of 2023....Restructuring expense was $7.7 million for the third quarter of 2022 compared to no expense in the comparable period in 2021. The restructuring plan announced during the quarter was designed to reduce costs and align resources with the Company’s anticipated product development milestones for exebacase and CF-370 and to help preserve the value of the Company’s drug discovery operations."

Commercial • IND • Cystic Fibrosis • Infectious Disease

ContraFect Data Presentations at the 32nd Annual ECCMID Meeting Highlight the Potential of Engineered Lysin CF-370 to Improve Clinical Outcomes and Suppress Antimicrobial Resistance Compared to Antibiotics Alone (GlobeNewswire) - "Using the 28-day serial passage method discussed above, the Company’s DLAs, including CF-370 and the lead molecules from its amurin peptide program, all demonstrated an extremely low propensity for developing decreased susceptibility to Gram-negative pathogens associated with respiratory infections in Cystic Fibrosis patients - P. aeruginosa, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. All DLAs tested had no change to MIC values compared to MIC increases ranging from 32-fold to 256-fold for levofloxacin and ciprofloxacin."

Preclinical • Cystic Fibrosis • Infectious Disease

ContraFect Announces Multiple Presentations of New Data Demonstrating the Potential of Its Direct Lytic Agents (DLAs) to Address Antimicrobial Resistance at the 32nd Annual ECCMID Meeting (GlobeNewswire) - "ContraFect Corporation...announces today that the Company has been selected for an oral presentation and six poster presentations at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) Annual Meeting to be held from April 23-26, 2022 in Lisbon, Portugal. The data being presented will feature exebacase...CF-370, an engineered lysin product candidate demonstrating potent in vitro bactericidal activity against resistant Gram-negative pathogens, as well as lead compounds from the Company’s proprietary amurin peptide program."

Preclinical • Cystic Fibrosis • Infectious Disease

Lysin CF-370 exhibits a low propensity for decreased susceptibility in Gram-negative (GN) ESKAPE pathogens (ECCMID 2022) - No abstract available

Infectious Disease

Lysin CF-370 suppresses in vitro resistance in Pseudomonas aeruginosa to meropenem, tobramycin and levofloxacin (ECCMID 2022) - No abstract available

Preclinical

In vivo efficacy of CF-370 alone and in addition to amikacin in the rabbit acute pneumonia model caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa, AR-769 (ECCMID 2022) - No abstract available

Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

ContraFect Reports Fourth Quarter 2021 and Full Year 2021 Financial Results and Provides Business Update (GlobeNewswire) - "The manufacturing process for CF-370 has also moved forward towards enabling an Investigational New Drug (IND) application later this year."

IND • Cystic Fibrosis • Infectious Disease

Direct Lytic Agents: Novel, Rapidly Acting Potential Antimicrobial Treatment Modalities for Systemic Use in the Era of Rising Antibiotic Resistance. (PubMed, Front Microbiol) - "Lysins were originally described as having activity against Gram-positive pathogens and of those, exebacase, is the first to have advanced into Phase 3 of clinical development. Importantly, novel DLAs targeting Gram-negatives, including the lysin CF-370 and the amurin peptides, are active in biological matrices (blood/serum) and, as such, offer promise for therapeutic use as systemically administered agents for the treatment of life-threatening invasive infections. In this review, DLAs are discussed as potential new classes of antimicrobial biologics that can be used to treat serious systemic infections."

Journal • Review • Infectious Disease • Pneumonia

ContraFect’s New Data Presented at NACFC Demonstrate Potential of Direct Lytic Agents to Treat Pulmonary Infections in Patients with Cystic Fibrosis (GlobeNewswire) - "ContraFect Corporation...announces today that data from the Company’s DLA programs, including lysin CF-370 and amurin peptide AM1, demonstrate the potential for their development as treatments for pulmonary infections associated with cystic fibrosis. These data were recently presented at the North American Cystic Fibrosis Conference (NACFC) which was held virtually from November 2-5, 2021....The data further support the in vitro activity profile of CF-370 and AM1 against specific Gram-negative pathogens, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Achromobacter spp."

Preclinical • Cystic Fibrosis • Respiratory Diseases

[VIRTUAL] Direct lytic agents exert potent bactericidal activity vs gram-negative pathogens causing pulmonary infections in CF patients, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans (NACFC-I 2021) - "The anti staphylococcal lysin exebacase is the first DLA to enter human clinical trials and is now in Phase 3 for the treatment of Staphylococcus aureus bacteremia and endocarditis, used in addition to traditional antibiotics. Lysin CF-370 and amurin peptide AM1 are active against some of the most prevalent gram-negative pathogens associated with airway infection in CF. These findings suggest that these agents may have the potential to address the unmet need for treatments for pulmonary exacerbations of CF caused by MDR gram-negative pathogens."

Clinical • Cardiovascular • Infectious Disease • Respiratory Diseases

[VIRTUAL] Lysin CF-370 In Vivo Efficacy Against a Carbapenem-resistant Pseudomonas aeruginosa in a Rabbit Infective Endocarditis Model (WMF 2021) - "This study provides further evidence of the in vivo efficacy of an iv-administered lysin targeting a Gram-negative pathogen, as CF-370 synergized with meropenem in a rigorous, high-inoculum model of multi-system pseudomonal infection. A three-day strategy of daily dosing with CF-370 + meropenem was the most efficacious regimen in decreasing bacterial densities in cardiac vegetations. Overall, these data support further evaluation of CF-370 for treatment of serious P. aeruginosa infections."

Preclinical • Cardiovascular • Infectious Disease

[VIRTUAL] Lysin CF-370 Exhibits Broad Spectrum Antimicrobial Activity Against Gram-Negative (GN) ESKAPE Pathogens (WMF 2021) - "Lysin CF-370 is broadly active against clinical as well as MDR and XDR isolates of P. aeruginosa, K. pneumoniae, E. cloacae, A. baumannii and E. coli. These findings support the continued development of CF-370 for the treatment of serious and life-threatening infections caused by drug-resistant Gram-negative pathogens."

Infectious Disease • Pneumonia

[VIRTUAL] Lysin CF-370 exhibits potent bactericidal activity against clinical MDR and XDR Pseudomonas aeruginosa isolates including carbapenem- and/or colistin- resistant forms (ECCMID 2021) - "The activity of lysin CF-370 against MDR and XDR P . aeruginosa isolates was demonstrated using multiple different in vitro susceptibility testing formats . These findings support the development of CF-370 for the treatment of serious infections caused by drug-resistant P ."

Clinical • Infectious Disease

[VIRTUAL] Lysin CF-370 Exhibits Broad Spectrum Antimicrobial Activity Against Gram-Negative (GN) ESKAPE Pathogens (WMF 2021) - "There is no abstract associated with this presentation."

Infectious Disease

[VIRTUAL] CF-370, a systemically administered lysin with in vivo efficacy against a carbapenem-resistant Pseudomonas aeruginosa strain in a rabbit pulmonary infection model (ECCMID 2021) - No abstract available

Preclinical • Infectious Disease • Respiratory Diseases

ContraFect Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Business Update (BioSpace) - "R&D expenses for the full year 2020 were $22.6 million compared to $18.1 million for the full year 2019. This increase was again primarily attributable to...process development and small-scale batch manufacturing for...CF-370..."

Commercial • Cystic Fibrosis