Lung infections are a major problem for patients with cystic fibrosis (CF) and can ultimately lead to their death. Pathogens often develop resistance to the currently used antibiotics, which makes the prevention and treatment of infections difficult. As covered by an indepth report into the field, monoclonal antibodies, like KaloBios’ KB001, may circumvent this problem and therefore represent significant commercial opportunities.

KaloBios Pharmaceuticals, a privately held biopharmaceutical company, has announced the initiation of a Phase I/II clinical trial of KB001, a high-affinity antibody fragment that the company is developing for the treatment of Pseudomonas aeruginosa infections. As with much drug development in CF, this trial is being conducted in conjunction with the Cystic Fibrosis Foundation.
CF is an inherited disease of the endocrine glands that is caused by genetic mutations and leads to a wide range of problems, including respiratory, liver and gastrointestinal symptoms. However, CF has the most significant impact on the lungs where infections (commonly caused by Pseudomonas aeruginosa and Staphylococcus aureus) can lead to respiratory failure.

Current interventions directed at reducing mortality in people with cystic fibrosis are invariably aimed at preventing, eradicating and controlling respiratory infections through prolonged treatment with high doses of antibiotics such as tobramycin. However, these face mounting rates of antibiotic resistance, particularly in Pseudomonas aeruginosa infections.

Interest in alternative strategies is therefore high. KB001 is one of several monoclonal antibodies in development for the treatment of Pseudomonas infection. These products are similar to the antibodies that the human immune system uses to fight off pathogens and are attractive due to their high specificity. Furthermore, the cost and mode of administration that typically limits their application in wider populations can be justified by the high, well-defined unmet need seen in CF.

However, KB001 still focuses on infection, rather than cystic fibrosis. Assuming it reaches the market, it will not only have to be positioned alongside antibiotics, but find a role alongside interventions targeting cystic fibrosis mechanisms as well. Vertex recently published preliminary data from a study of one such product. The success of Phase II trials testing its small-molecule oral drug VX-700, featured an average 10% improvement in lung function – signaling the potential to offset the demand for treatments for infections that KB001 is intended to treat.

This suggests that in the longer term, KaloBios may need to consider non-CF populations for supplemental revenues. One such group could be those patients on a ventilator in intensive care units, for which KB001 is in Phase I of development.

Related reserach: Monoclonal Antibodies Report Part I