Anti-Pseudomonas Activity of KaloBios'/sanofi pasteur's KB001 May Prevent Serious Lung Infections and Limit Damaging Inflammation
-- Clinical Experience with KB001 in Mechanically Ventilated Patients and Cystic Fibrosis Sufferers Presented at American Thoracic Society Meeting (ATS) --
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 17, 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.
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.”
KB001, a Humaneered™ antibody fragment, is designed to fight Pa by blocking a virulence mechanism (the Type-Three Secretion System or TTSS) on the bacterium's external surface that enables Pa to evade human immune defenses by killing white blood cells and epithelial cells, and triggering tissue-damaging inflammation. By blocking Pa's killing mechanism, KB001 is intended to reduce the damage done to the lungs by Pa and potentially enable the patient's own immune system to effectively fight and clear the bacteria from sites of infection. KB001 avoids known mechanisms of antibiotic resistance and does not contribute to broad-spectrum resistance, thereby allowing use as a single agent or in synergy with antibiotics in the preventive or therapeutic setting.
KaloBios Pharmaceuticals is collaborating with sanofi pasteur, the vaccines division of the sanofi-aventis, on the development and commercialization of KB001. Sanofi pasteur is responsible for the development and commercialization of KB001 and is initially focused on hospital indications, including the prevention of Pa pneumonias in mechanically ventilated patients. KaloBios is focused on developing and commercializing KB001 for use in treating patients with cystic fibrosis and bronchiectasis, an obstructive lung disease aggravated by bacterial infections.
KaloBios Pharmaceuticals, Inc., a U.S. based, private monoclonal company, uses its biologic capabilities and its proprietary platform technology to develop first-in-class human antibody therapeutics. The company has multiple programs that have been in seven Phase 1 or 2 clinical trials in the last few years. KB001 is a PEGylated monoclonal antibody fragment directed against Pseudomonas aeruginosa that is in development for patients with cystic fibrosis and patients in intensive care on a ventilator. KaloBios is also developing an anti-GM-CSF monoclonal antibody (KB003) for the treatment of patients with autoimmune and chronic inflammatory conditions, such as rheumatoid arthritis and asthma. KB004 is a monoclonal antibody that targets the onco-fetal protein, EphA3, which is aberrantly expressed in a wide variety of hematologic malignancies, including on leukemic stem cells, and solid tumors. The company's Humaneering™ technology is designed to offer advantages over other methods of human antibody creation in terms of immunogenicity, potency, and manufacturing yields. For more information, visit http://www.kalobios.com.
Contact: KaloBios Pharmaceuticals, Inc.
David W. Pritchard, 650-243-3100
President and CEO
Joan E. Kureczka, 415-821-2413
Posted: May 2010