CD201 For Multi-Drug Resistant Gram-negative Bacterial Infections
CD201 is a novel, bispecific antimicrobial immunotherapy being developed for the treatment of multi-drug resistant (MDR) bacterial infections, including those caused by MCR-1-producing pathogens.
CD201 may circumvent existing bacterial resistance mechanisms and introduce a new mechanism of immune-mediated killing, potentially providing a novel tool for fighting MDR pathogens. These include pathogens resistant to carbapenems, a staple, standard-of-care therapy for Gram-negative infections, as well as colistin, an antibiotic used as last-resort therapy.
CD201 is the first development candidate from our Cloudbreak™ immunotherapy discovery platform. The Cloudbreak immunotherapy platform is similar to certain cancer immunotherapies in that it uses components with two binding sites, one that binds to a bacterial cell surface target and a second that binds to specific receptors on immune cells. CD201 works by binding to a target present on a wide range of Gram-negative bacteria, including MCR-1-positive strains, while simultaneously recruiting immune components to an infection site to coordinate localized host-mediated infection clearance.
CD201 has demonstrated potent antibacterial activity in vitro against a number of clinically significant Gram-negative bacteria, including Klebsiella, Acenitobacter, Pseudomonas and Enterobacter spp., as well as against MDR pathogens, including those harboring plasmids containing the mcr-1 gene. CD201 has also demonstrated preliminary efficacy and safety in a number of animal models of infection.
CD201 has two components that are joined by a chemical linker: a targeting moiety (TM) that recognizes a cell surface target and an effector moiety (EM) that is recognized by the immune system. The coupling of the TM to the EM results in a bispecific molecule that can direct the immune system specifically to the targeted pathogen.
- Direct Kill: Novel TM tightly binds Gram-negative pathogens to kill bacteria and modulate a septic response
- Immune Engagement: EM recruits and initiates an immune system response
- Potentiation: Enhances permeability of standard of care therapeutics to provide additional efficacy
Multi-Drug Resistant Gram-negative Bacteria
Many strains of bacteria have mutated over time and have developed resistance to existing antibiotics resulting in limited therapeutic options for patients and a growing public health crisis. Antibiotic resistance is seen in both community- and hospital-acquired infections and is of most concern for patients with bacterial infections that are resistant to a number of antibiotic classes. These bacteria are referred to as multi-drug resistant (MDR). MDR Gram-negative bacteria include strains of Acinetobacter, Pseudomonas and Klebsiella, which can lead to serious, life-threatening infections in the absence of effective new treatments.
Summary of Preclinical Research
CD201 has demonstrated potent antibacterial activity in vitro against a number of clinically significant Gram-negative bacteria, including Klebsiella, Acenitobacter, Pseudomonas and Enterobacter spp. and resistant pathogens (including bacteria resistant to carbapenems and colistin), as well as pathogens harboring the mcr-1 plasmid. CD201 also has demonstrated preliminary efficacy and safety in a number of animal models of infection.
ECCMID 2017 | Vienna, Austria | April 2017
- Antimicrobial Activity of CD201, a Novel Lipopolysaccharide-Binding Antibacterial Immunotherapy, Against Recent Gram-Negative Clinical Isolates, Including Colistin-Resistant Strains
- In Vitro Characterization of Antibacterial Activity, Cidality and Spontaneous Resistance Potential of CD201, a Novel Lipopolysaccharide-Binding Antibacterial Immunotherapy