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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, CA (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."
About KB001
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.
About KaloBios
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 human monoclonal (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
www.kalobios.com.
Contact:
Media Contact:
David W. Pritchard
President and CEO
KaloBios Pharmaceuticals, Inc.
(650) 243-3100
Joan E. Kureczka
Kureczka/Martin Associates
(415) 821-2413
Mob: (415) 690-0210
