Potential Once-weekly Asthma Treatment Found Safe, Well-Tolerated in Study
SAN DIEGO and VIENNA, Austria—September 14,
2009—Altair Therapeutics, Inc., a privately-held,
biopharmaceutical company developing novel therapeutics for
respiratory diseases, today an nounced positive results from a
phase I multiple dose safety and pharmacokinetic study of its lead
product,once-weekly inhaled AIR645 in healthy adults and mild
asthmatics. The results were presented today by Dr. Michael Hodges,
M.D., Chief Medical Officer for Altair Therapeutics at the European
Respiratory Society Annual Congress in Vienna.
AIR645 is a non-steroidal dual inhibitor of cellular responses to
interleukin (IL)-4 and IL-13. These pro-inflammatory cytokines
orchestrate the adaptive immune response to inhaled allergens and
viruses and the development of chronic inflammation in asthma,
rhinitis and other respiratory disorders. The randomized,
placebo-controlled trial evaluated the safety, tolerability,
bioavailability and pharmacodynamic activity of nebulized AIR645 at
multiple dose levels in 32 healthy adult subjects (0.3, three, 10,
and 20 mg/dose) and eight mild asthma subjects (20mg/dose).
Subjects were sequentially randomized (six active: two placebo) and
received six doses on study days one, three , five, eight, 15 and
22.
AIR645 was safe and well tolerated. No dose-limiting toxicities or
safety signals were detected in this clinical study. Adverse
effects were mostly mild and none were considered severe,
significant, or serious and no subjects were discontinued due to
adverse events. AIR645 exposure in sputum was found to be
dose-dependent, and no accumulation of drug was evident. AIR645
half-life in sputum was calculated to be approximately 5 days.
AIR645 concentration was >1000-fold higher in sputum than in
plasma, indicating very low systemic bioavailability of the drug.
Following repeated inhalation of AIR645 evidence of
anti-inflammatory biomarker activity was seen in subjects with mild
asthma (those that had baseline elevations of biomarkers),
including reductions in serum total IgE, sputum eosinophils or
level of 15-HETE in sputum.
"The AIR645 pharmacokinetics and distribution profile demonstrated
in this study are consistent with preclinical findings and support
effective once-weekly or once-daily administration of this
2'-O-methoxyethyl modified oligonucleotide in humans," commented
Susan Gregory, Ph.D., Chief Scientific Officer for Altair
Therapeutics. "We believe that IL-4Rα inhibition can
prevent and retard asthma pathogenesis and will prove to be a
valuable therapeutic approach to asthma, chronic obstructive
pulmonary disease and other respiratory disorders."
"The safety and PK data from this study underscore the potential of
AIR645 as a new, safe and effective non-steroidal anti-inflammatory
control medication for asthma," said Dr. Hodges. "The dosi ng
flexibility afforded by the projected long tissue half-life of this
drug opens the door to improved patient compliance using a
once-daily inhaler or using once-weekly nebulized
formulations."
"AIR645 is based upon a proprietary anti-sense molecular design
– termed ‘MOE gapmer’ – that greatly
improves potency, stability, safety and tolerability in vivo," said
Joel F. Martin, Ph.D., President and CEO of Altair Therapeutics.
"AIR645 is the first such MOE gapmer oligonucleotide to be
administered by inhalation in man and has now demonstrated
favorable safety and pharmacokinetic profiles. The results are
particularly remarkable because AIR645, a low cost-of-goods drug,
inhibits a target that, to date, has been approachable only by
expensive biologics."
About AIR645
AIR645 is a dual inhibitor of IL-4 and IL-13, pro-inflammatory
cytokines which are implicated in the pathogenesis of asthma,
allergic rhinitis and other inflammatory disorders. AIR645 is a
2'-O-methoxyethyl second-generation antisense drug targeting the
mRNA that encodes the alpha subunit of the human IL-4 receptor
(IL-4Rα). IL-4Rα is the signaling chain
that is shared by the IL-4 and IL-13 receptors and is required for
cellular responses to IL-4 and IL-13. AIR645 has the potential for
less frequent administration with improved local and systemic
safety. AIR645 was discovered by Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) and licensed to Altair Therapeutics.
About Altair Therapeutics
Based in San Diego, Altair Therapeutics, Inc. is a privately-held
biopharmaceutical company developing novel therapeutics to treat
human respiratory diseases. Altair Therapeutics’ lead product
is AIR645, the first in a new class of inhaled drugs that
incorporate proprietary, second-generation antisense
chemistry.
Erik Clausen
Partner & General Manager, San Francisco Office
College Hill Life Sciences
201 Spear Street, Suite 1100, San Francisco, CA 94105
Office: (415) 230-5385
Mobile: (781) 608-7091
Posted: September 2009
