IND Enabling Development of CF-296, a Lysin for the Treatment of Invasive Staphylococcus Aureus (S. Aureus) Infections
Abstract
As healthcare delivery increasingly involves invasive procedures and implantable devices, the number of patients at risk for Staphylococcus aureus (S. aureus) bacteremia and its secondary invasive infections including infective endocarditis (IE), osteomyelitis (OM), prosthetic joint infections (PJI) and infections on implantable medical devices and catheters is likely to grow. Further complicating the situation is the emergence of antibiotic resistance, with strains such as Methicillin-Resistant S. aureus (MRSA), vancomycin insensitive S. aureus, and other resistant S. aureus strains. MRSA is categorized as a “serious threat” by the US Centers for Disease Control and Prevention (CDC). In addition to resistance, many of these invasive S. aureus infections are associated with biofilms, a protective mechanism for bacteria that are characterized by densely packed bacterial cells that are enclosed within a complex matrix of dead bacteria and excess cell wall components, reducing the efficacy of conventional antibiotics. Invasive S. aureus infections are particularly problematic as currently approved antibiotics have demonstrated limited efficacy in treating these infections, particularly due to a lack of activity on biofilms, requiring long courses of high doses of antibiotics and surgical interventions to eradicate the infection. There is thus a significant unmet need for novel anti-staphylococcal treatments. There are few new drugs in the clinical trials pipeline for the treatment of OM and PJI due to the challenges in treating these infection. ContraFect is developing a series of novel lysins with specific activity against S. aureus, demonstrating a range of features making them ideal for treatment of invasive infections: (1) rapid antibiotic activity, (2) potent ability to rapidly clear biofilms, (3) specificity against S. aureus strains, (4) low tendency for development of resistance, as well as (5) potent synergy with conventional anti-staphylococcal antibiotics. These lysins are also active against antibiotic-resistant strains such as MRSA as well as emerging resistant strains. The Company’s lead lysin, CF-301, is currently being studied in a Phase 2 multicenter, multinational, randomized, controlled clinical trial in patients with S. aureus bacteremia including endocarditis. ContraFect has engineered a second-generation lysin, CF-296, and preliminary data indicate that CF-296 exhibits similar activity and potency as the first-generation lysin, CF-301, while exhibiting the potential for higher exposures and repeat-dose treatments for invasive infections. Based on our understanding of the potential efficacy profile of CF-296 when used in conjunction with conventional anti-staphylococcal antibiotics, we expect improved clinical outcomes for the treatment serious invasive S. aureus infections. In this application, we propose the preclinical development of CF-296 towards the submission of an Investigational New Drug (IND) application through the following Specific Aims: Specific Aim 1: Profile microbiologic activity of CF-296 in clinically relevant strains. Specific Aim 2: Develop a CF-296 scalable manufacturing process and generate material for use in toxicity studies. Specific Aim 3: Conduct IND-enabling Good Laboratory Practices (GLP) nonclinical studies to support IND filing. Specific Aim 4: Assessment of the immunogenic potential CF-296 by measuring anti-drug antibody (ADA), and IgE responses in rats and dogs. Specific Aim 5: Develop robust pharmacology data to support clinical indications, IE, OM, and PJI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910139
Entities
People
- Raymond Schuch
Organizations
- United States Army