KaloBios' KB001 Antibody Shows Encouraging Safety And Activity In New Approach To Fighting Pseudomonas Infection In Cystic Fibrosis Patients
Article Date: 18 Oct 2009 - 0:00 PDT
Phase 1/2 clinical trial results with KB001, a Humaneered™, high-affinity antibody fragment under development by KaloBios Pharmaceuticals, Inc. in cystic fibrosis patients showed an acceptable safety profile as well as trends toward reducing tissue inflammation and clearance of the bacterium. Results of the multi-center, randomized, double-blind, single-dose, placebo-controlled study are being presented today at the North American Cystic Fibrosis Conference in Minneapolis, MN. KaloBios is developing KB001 for the treatment and/or prevention of Pseudomonas aeruginosa infections in both cystic fibrosis patients and intensive care patients on ventilation, for whom Pseudomonas-caused pneumonia is a major costly health care problem.
"KB001 is designed to fight Pseudomonas aeruginosa (Pa) by blocking a virulence mechanism (the Type Three Secretion System or TTSS) on the bacterium's external surface that enables Pa to perforate and kill white blood cells and epithelial cells, and trigger tissue-damaging inflammation," said Dr. Geoff Yarranton, Kalobios' chief scientific officer. "By blocking Pa's killing mechanism, KB001 is intended to reduce the inflammation and exacerbations that are associated with the damage done to the lungs by Pa, and potentially enable the patient's own immune system to effectively fight and clear the bacterium from sites of infection. This contrasts with antibiotics like tobramycin that directly kill Pa, but quickly lose effectiveness if the bacteria become resistant to the drug."
The Phase 1/2 study enrolled two cohorts of approximately 12 patients who were randomized at a 2:1 ratio to receive a single IV infusion of KB001 or placebo at either 3.0 mg/kg or 10 mg/kg. Patients were followed for eight weeks. Results showed KB001 to be safe and non-immunogenic. An analysis of exploratory endpoints showed that there was an encouraging anti-inflammatory impact as measured by dose-related reductions in inflammatory markers, including neutrophils, IL-8, elastase, MPO, macrophages, and IL-1. There was also a trend in reducing mucoid and total Pa burden at day 56.
"We are very pleased with these initial clinical results for KB001, which we believe support conducting larger randomized clinical trials to further evaluate KB001's safety and clinical benefits for patients with cystic fibrosis," said Tillman Pearce, KaloBios' chief medical officer. "KB001 is a highly novel approach to treating Pseudomonas and now has shown promising data in both ventilator-associated pneumonia patients and cystic fibrosis patients."
Pseudomonas infection is a major unmet medical need with strains found all over the world that are resistant to common antibiotics. KaloBios is actively seeking a partner to help move this program forward and to ultimately capture the potential market of over $500 million that would exist for a safe and effective anti-Pseudomonas therapy.
For more information about KB001, please visit the KaloBios website.