KaloBios Pharmaceuticals' KB001 promising in prevention of serious lung infection

May 18 2010

The data from the initial clinical studies with KB001, a novel antibody fragment against PcrV on Pseudomonas aeruginosa (Pa) bioengineered by KaloBios Pharmaceuticals, Inc. and partnered with sanofi pasteur, demonstrated promising therapeutic activity in the prevention of serious lung infection in mechanically ventilated patients colonized with the bacterium and in limiting potentially damaging inflammation in patients with cystic fibrosis, where Pa plays an important role in the disease.

“Pa quickly and readily develops resistance to most antibiotics upon chronic administration, and KB001 may offer a potential new alternative for treating these serious lung infections.”

The findings are being presented in multiple sessions at the American Thoracic Society Meeting being held from May 14-19 in New Orleans, LA.

"By binding to and blocking the function of PcrV, an important element of the type-three secretion system associated with Pa virulence, KB001 offers a novel approach in the treatment of serious Pa infections," said Tillman Pearce, MD, Chief Medical Officer of KaloBios. "The data being presented at ATS not only highlight the therapeutic potential for KB001 in preventing Pa pneumonia in mechanically ventilated patients and for treating Pa lung infection in patients with cystic fibrosis, but the fact that KB001 may represent an alternative to the use of antibiotics which are often rendered ineffective in these settings due to resistance development."

KB001 in Patients on Mechanical Ventilation

In an oral presentation planned for Sunday May 16, Jean Chastre, M.D., Professor of Medicine, Director, Medical Intensive Care Unit, Hôpital Pitié-Salpêtrière, reported data from a pilot study demonstrating the potential for KB001 to prevent serious Pa pneumonia in mechanically ventilated patients who were confirmed to be colonized with the bacterium. The randomized, double-blind, 4-week study, conducted at 10 centers in France, compared a single IV infusion of KB001 at 3 mg/kg or 10 mg/kg to placebo. Greater than 90% of patients in all cohorts received antibiotics within 14 days from study entry, with the majority on mechanical ventilation for at least 7 days.

The 35 evaluable patients tolerated the infusions without incidence of related serious adverse events and none developed anti-KB001 antibodies. Trends towards improved clinical outcomes were observed in KB001-treated subjects, with 46% of patients treated with high-dose KB001 alive at Day 28 without a Pa infection compared with only 20% of placebo-treated patients. The proportion of patients with Pa pneumonia was lower in KB001-treated patients (33% and 31% for low and high doses) compared with placebo-treated patients (60%).

KB001 in Patients with Cystic Fibrosis

In a poster presentation, also scheduled for Sunday May 16, Carlos Milla, M.D., Associate Professor of Pediatrics Pulmonary Medicine, Lucille Salter Packard Children's Hospital at Stanford, and collaborators reported results of a multicenter pilot study designed to assess the potential benefit of KB001 in treating patients with cystic fibrosis. Twenty seven subjects with a sputum Pa burden of ≥1 x 10³ cfu/gm on screening and on stable CF therapy were randomized in dose-escalating cohorts to receive single IV infusions of placebo or KB001 at either 3 mg/kg or 10 mg/kg. Clinical, pharmacokinetic and immunogenicity outcomes were assessed. Pharmacodynamic assessment of sputum microbial ecology and changes from baseline in Pa burden and inflammation were also assessed.

The single infusion of KB001 had a tolerable safety profile and no patient developed anti-KB001 antibodies. Microarray analysis of baseline sputum revealed a large bacterial community with 81-938 taxa identified. Within this extreme diversity, the mean Pa burden was log₁₀ = 7.7 and Pa represented on average 33% of the total bacteria in the sputum as determined by clonal analysis. Dose-dependent trends towards reduction in mucoid Pa burden and inflammatory parameters were observed over the 28 day observation period in the KB001 treated patients.

"Pseudomonas aeruginosa is one of the most important causes of serious lung infections that, in patients requiring mechanical ventilation, can be life-threatening and can add tens of thousands of dollars of cost to a hospital stay. The bacterium also chronically infects the lungs of about 80% of adult cystic fibrosis patients where it is believed to play a direct role in the exaggerated inflammatory response associated with progressive pulmonary failure," said David Pritchard, KaloBios President and Chief Executive Officer. "Pa quickly and readily develops resistance to most antibiotics upon chronic administration, and KB001 may offer a potential new alternative for treating these serious lung infections."

SOURCE KaloBios Pharmaceuticals, Inc.,