KaloBios Pharmaceuticals, Inc. has announced phase 2a results of KB001, the recombinant, human PEGylated monoclonal antibody fragment. The study offers potential as an alternative to antibiotics for preventing or reducing  pneumonias in mechanically ventilated intensive care unit (ICU) patients heavily colonized with Pseudomonas aeruginosa (Pa).

Results of the phase II a study, sponsored in its entirety by KaloBios and conducted at 10 ICUs across France, have been published online and will appear in the August issue of Critical Care Medicine.

The study conducted from April 2008 to July 2009 found no clinically significant differences in safety between the KB001 treated patients and those treated with only standard of care. In addition, the study showed KB001 to be well tolerated and non-immunogenic, and have favorable pharmacokinetics and predictable dose-dependent penetration into the lungs of ICU patients heavily colonized with Pa. While the 39-patient randomized, placebo-controlled, double-blind study was insufficiently powered to show statistical significance related to efficacy, patients receiving intravenous infusions of KB001 tended to have better clinical outcomes. Investigators reported that 33.3 per cent of the 3 mg/kg (n=12) group and 46.2 per cent of the 10 mg/kg (n=13) group were alive at day 28 and Pa infection free, versus only 20 per cent of the placebo (n = 10) group.

“Based on these results, KB001 shows promising potential for reducing Pa pneumonia incidence in mechanically ventilated ICU patients colonized with Pa bacterium,” said Néstor Molfino, chief medical officer of KaloBios. “Our partner Sanofi Pasteur is planning to pursue this approach in larger clinical trials, while we will continue development in treating cystic fibrosis patients with chronic Pa.”

“Despite the availability of antibiotics against Pa, the morbidity and mortality of ventilator associated pneumonia remains high and antibiotic resistance is rising. KB001 specifically targets Pa virulence factors of the type III secretion system (TTSS) that are required for the bacterium to cause host damage and death. The mechanism of action of the drug avoids the multiple efflux pumps of Pa that the bacterium uses to create antibiotic resistance. Thus, KB001 may offer a new approach to preventing or treating serious infections in ICU patients with pulmonary Pa colonization without contributing to the growing problem of multi-drug resistance,” said Geoff Yarranton, Chief Scientific Officer of KaloBios.

As demonstrated in preclinical studies, the TTSS of Pa is a major determinant of that bacterium’s virulence and is required for systemic Pa spread. In human Pa infections, functional TTSS expression corresponds to poor prognoses. TTSS consists of a complex, needle-like apparatus that is able to inject up to four different exotoxins directly into cells. Furthermore, in the absence of exotoxins, the TTSS can directly mediate macrophage and neutrophil cytotoxicity leading to bacterial swarming and direct cell-membrane perforation. The needle-tip protein, PcrV, is an essential component of all these TTSS functions. KB001 works by specifically binding to Pa-PcrV and inhibiting its function, rendering the bacterium non-virulent.  Preclinical studies with KB001 have demonstrated its ability to prevent death, restore normal body temperature, and enhance bacterial clearance from the lungs in in vivo models of acute pulmonary infection.

KaloBios Pharmaceuticals, Inc., is developing a portfolio of proprietary, patient-targeted, first-in-class monoclonal antibodies (mAbs) designed to significantly improve the lives of seriously ill patients with difficult-to-treat diseases.