KaloBios’ KB001 shows promise against Pa pneumonia

"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.

Source: KaloBios