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Novel Apolipoprotein A-I Therapy, CSL112, May Represent New Option for Reducing Recurrent Heart Attack Risk, Early CSL Studies



    Novel Apolipoprotein A-I Therapy, CSL112, May Represent New Option for
         Reducing Recurrent Heart Attack Risk, Early CSL Studies Show

Multiple studies of CSL112 presented at the American Heart Association 2012
Scientific Sessions

PR Newswire

LOS ANGELES, Nov. 5, 2012

LOS ANGELES, Nov. 5, 2012 /PRNewswire/ -- Infusions of a novel formulation of
apolipoprotein A-I (apoA-I) – the main component of high-density lipoprotein
(HDL) – rapidly increased the presence of key biomarkers associated with
reverse cholesterol transport, a process by which cholesterol is removed from
arteries and transported to the liver for clearance, according to data from a
Phase 1 study sponsored by CSL Limited. Rapid removal of cholesterol following
a heart attack may play a role in stabilizing vulnerable plaque lesions and
lowering the high risk of subsequent attacks.

"In our study, CSL112 dramatically elevated measures of cholesterol efflux
capacity, a newly recognized marker of HDL function, and rapidly raised blood
levels of apoA-I," said Andreas Gille, MD, PhD, CSL Head of Clinical and
Translational Science Strategy, and lead study author. "This is a very
exciting early finding when viewed in the context of reducing the risk of
recurrent heart attacks. We look forward to further developing CSL112 with the
goal of meeting a significant unmet medical need in the acute coronary
syndrome patient population."

Data from two CSL112 Phase 1 studies presented at the American Heart
Association (AHA) meeting demonstrated a positive safety and pharmacokinetic
(PK) profile for CSL112, warranting progression to Phase 2 development. CSL112
will be studied for the early reduction of recurrent cardiovascular events in
acute coronary syndrome (ACS) patients.

Study Design and Key Findings
Biomarkers of cholesterol movement following infusions of CSL112 were observed
in 36 healthy subjects. Three dosing regimens were studied, including 4
once-weekly infusions of 3.4g, 4 once-weekly infusions of 6.8g, and 8
twice-weekly infusions of 3.4g. Subjects were randomized to CSL112 or placebo
(3:1, respectively). All biomarker responses were dose dependent and showed
similar magnitude and time course after the first and last infusions.

An overall elevation in cholesterol efflux capacity, PreBeta1-HDL, and HDL in
serum or plasma was observed among all dosing regimens. PreBeta1-HDL was
increased 20-fold among dosing regimens. Cholesterol efflux capacity and
PreBeta1-HDL peaked immediately following infusion and returned to near
baseline at 24 hours. HDL level increased following PreBeta1-HDL, peaked at 24
to 48 hours, and sustained elevation 72 hours after infusion.

Safety and PK profiles were separately evaluated in the 36 healthy patients
receiving the three dosing regimens of CSL112.  No treatment-emergent serious
adverse events (AE) were reported, no abnormalities were observed in serum
biochemistry, hematology and urine parameters, and no significant changes were
seen in platelet function, vital signs or ECG associated with CSL112
treatment. The most common AE reported was vessel puncture site hematoma (18
of 36), which was reported by similar proportions of patients receiving either
CSL112 or placebo.

"Development of products that increase cholesterol efflux from the artery wall
represents an emerging area in atherosclerosis discovery," said Dr. Samuel
Wright, PhD, Global Strategic Director for Cardiovascular Therapeutics at CSL
Limited and study co-author. "Prior approaches have centered on addressing
only HDL cholesterol levels. CSL112 holds promise as a new therapy that may be
used in addition to other treatments, such as anti-platelet agents, to provide
early event reduction."

Additional CSL112 Research
Data from a randomized single ascending dose study of 57 healthy subjects were
also presented at the AHA 2012 Scientific Sessions and demonstrated that a
single infusion of CSL112 at dose levels of 5 to 135 mg/kg immediately caused
dose-proportional elevation in apoA-I and changes to key biomarkers of the
early steps in reverse cholesterol transport. These changes from baseline
occurred in a dose- and time-dependent manner and were maintained for at least
72 hours after infusion of CSL112 at 40 mg/kg and higher. Notable biomarker
changes included elevations in PreBeta1-HDL (maximum=3,600%) and global
cholesterol efflux capacity from macrophages (maximum=270%).  

In another study presented at the meeting, CSL112 was observed to have strong
anti-inflammatory properties in human blood ex vivo. This property of CSL112
may prove to be beneficial in the reduction of inflammation associated with
cardiovascular events.

"We are very encouraged by the early experience with CSL112 in the clinic and
are looking forward to completing the mid-stage studies that are now in
progress or being planned to start next year," said Chuck Shear, CSL Senior
Director and Therapeutic Area Head.

About CSL112
CSL112 is a novel formulation of apolipoprotein A-I (ApoA-I), the chief
component of high-density lipoprotein (HDL). It is purified from plasma and
reconstituted to form HDL suitable for intravenous infusion. As demonstrated
in pre-clinical and Phase 1 studies, CSL112 elevates cholesterol efflux
capacity, as well as additional steps in reverse cholesterol transport. CSL112
demonstrates strong anti-inflammatory activity, as well.

About CSL
Headquartered in Melbourne, Australia, CSL Limited is a global
biopharmaceutical company that develops, manufactures and markets biotherapies
to prevent and treat rare and serious human diseases. CSL owns major
facilities in Australia, Germany, Switzerland and the United States, and
employs over 11,000 people in more than 25 countries. Visit www.csl.com.au for
more information.

Contact

Sheila A. Burke
Director, Communications & Public Relations
Worldwide Commercial Operations
CSL Limited
C: 484-919-2618 (US)
Sheila.Burke at cslbehring.com

Eliot Harrison
MCS Healthcare Public Relations
C: 908-884-5252
eharrison@mcspr.com

Australian press inquiries
Sharon McHale
Senior Director, Public Affairs
CSL Limited
phone +61 3 9389 1506
mobile +61 409 978 314
sharon.mchale@csl.com.au

Investor Relations inquiries
Mark.Dehring@csl.com.au
Vice President, Investor Relations

SOURCE CSL Limited

Website: http://www.csl.com.au
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