A Fully Human Monoclonal Antibody Targeting PNAG
F598 is a fully human IgG1 monoclonal antibody selected for its ability to mediate killing of PNAG-expresssing microbial pathogens. In animal studies administration of monoclonal antibody F598 has been shown to reduce the impact of microbial challenges in several models, using a number of different microbes. Administering monoclonal antibody F598 to mice has led to reductions in mortality, the development of pneumonia, peritonitis, and corneal infections and reductions in signs of local or systemic infection.
Phase 1 and pilot phase 2 trials of F598 have been completed. The antibody was found to be well tolerated, and no serious adverse events were observed. A single infusion was noted to provide sustained serum levels for 2-3 months. Unlike vaccines which may take several weeks to induce protective immunity, administration of a monoclonal antibody provides immediate protection. Therefore, the antibody will be utilized in settings where an individual is at an immediate or near-term risk of developing an infection.
Monoclonal Antibody F598 Pipeline
| Compound | Indication | Discovery | Pre-Clinical | Phase 1 | Phase 2 | Phase 3 |
|---|---|---|---|---|---|---|
F598 |
ICU infections |
Discovery Phase complete
|
Pre-Clinical Phase complete
|
Phase 1 Phase in progress
|
Phase 2 Phase not started
|
Phase 3 Phase not started
|
F598 |
Prevention of infection after emergency abdominal surgery/abdominal trauma |
Discovery Phase complete
|
Pre-Clinical Phase complete
|
Phase 1 Phase in progress
|
Phase 2 Phase not started
|
Phase 3 Phase not started
|
Initial Indication – Healthcare Associated Infections (HAIs)
In 2007, the Centers for Disease Control and Prevention estimated that roughly 1.7 million Healthcare-Associated infections, from all types of microorganisms, including bacteria and fungi combined, caused or contributed to 99,000 deaths each year in the United States. While the overall incidence of infection has fallen slightly there have been no changes in pneumonia and gastrointestinal infections. Hospital-acquired or nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types display antimicrobial resistance, which can complicate treatment.
In an effort to reduce the incidence of HAIs, in 2008 Medicare initiated the Healthcare Associated Condition (HAC) Reduction Program. The hope was that financial penalties would encourage hospitals to initiate programs that would reduce the incidence of HAIs.
Utilization of monoclonal antibody F598 to reduce HAIs would be consistent with Medicare’s directive
Monoclonal Antibody F598 is Well Suited to Prevent HAIs
F598 has a long half life in the blood stream with microbial killing noted up to day 50. This suggests that a single infusion of F598 could provide protection for 2-3 months - a more than adequate time period to cover the risks associated with most hospital admissions both during and after discharge. F598 has been shown to be capable of killing a wide range of microbes, many of which are associated with HAIs.
Killing of Microbes by F598
- Staphylococcus aureus
- S. epidermidis
- Neisseria gonorrhoeae
- N. meningitidis
- Hemophilus influenzae type b
- Streptococcus pneumoniae
- S. pyogenes
- Bordetella pertussis
- Franciscella tularensis LVS
- Burkholderia cepacia complex
- Candida albicans
- Aspergillus flavus
- A. fumigatus
- Fusarium solani
- Enterococcus faecalis
- Escherichia coli
- Klebsiella pneumoniae
- Enterobacter cloacae
- Acinetobacter baumannii
- Mycobacterium avium
- Listeria monocytogenes
Our Initial Indication
Prevention of HAI’s in Intensive Care Unit Patients
We plan on utilizing monoclonal antibody F598 to prevent or mitigate infections in ICU patients. The incidence of HAIs in ICU patients is high - around 20%. That makes it a relevant and realistic population to study. As the majority of microbes causing HAI infections express PNAG, any intervention that can reduce HAIs would establish a new standard of care. This would be consistent with Medicare's directive to employ interventions that could reduce the incidence of HAIs. Unlike antibiotics that would be used once an HAI is identified, an antibody that can prevent those infections would be readily accepted by hospitals.
If this study can demonstrate a reduction in the morbidity/mortality of HAIs in ICU patients it would be a major health advance.