THE NEW ENGLAND JOURNAL OF MEDICINE PUBLISHES CLINICAL RESULTS ON KARO BIO'S

THE NEW ENGLAND JOURNAL OF MEDICINE PUBLISHES CLINICAL RESULTS ON KARO BIO'S  

LIPID LOWERING DRUG EPROTIROME 

Data demonstrate the potential for further reducing atherogenic lipids in
statin-treated patients who do not reach their LDL-cholesterol goals


STOCKHOLM, SWEDEN, March 10, 2010. The Swedish biotech company Karo Bio
(Reuters: KARO.ST) today announced the publication of results from a clinical
phase II trial evaluating the company's liver selective thyroid hormone receptor
agonist eprotirome and its ability to further reduce serum LDL cholesterol
levels in statin-treated patients. The results are published in the March 11,
2010 edition of the New England Journal of Medicine (NEJM).


The study was a randomized, placebo-controlled, double-blind multi-center trial
of three months duration, performed between November 2007 and June 2008. It was
designed to assess the safety and efficacy of the liver selective thyroid
receptor agonist eprotirome (KB2115) in lowering the serum concentration of LDL
cholesterol and other atherogenic lipids in hypercholesterolemic patients
already taking simvastatin or atorvastatin.  

Eprotirome is the first liver selective thyroid hormone receptor agonist that
has demonstrated pronounced effects on several atherogenic serum lipids. These
beneficial effects were observed at doses where no extra-hepatic thyroid
hormone-like effects were evident. Eprotirome is mainly distributed to the liver
where it exerts its beneficial effects on LDL-cholesterol and other atherogenic
lipoproteins. This is in contrast to the natural hormone triiodothyronine (T3)
and thyroxine (T4), which are widely distributed throughout different tissues.
Eprotirome's liver-selectivity is important for the avoidance of side effects
related to extra-hepatic thyroid hormone-receptor activation. A slight
selectivity for the thyroid hormone receptor (TR)-beta may also contribute to
the avoidance of side effects such as the TR-alpha mediated effects on the
heart.

The results published in the NEJM show that in statin-treated patients,
eprotirome substantially lowers serum LDL cholesterol, non-HDL cholesterol and
apo B and also reduces a number of other risk factors for cardiovascular disease
including serum triglycerides and lipoprotein(a) (Lp(a)). Furthermore, these
favorable changes in atherogenic lipids were achieved without evidence of
adverse thyroid hormone-like effects. 

“We are very excited by the results. Eprotirome has the potential to be a useful
drug in high-risk patients currently on statins but not able to reach their
LDL-goals. This is an area with a high unmet medical need”, commented Jens
Kristensen, VP Clinical Development and Chief Medical Officer of Karo Bio.

In all, 329 patients were screened for the study, of which 189 were randomized
and included in the trial. In addition to statin treatment, they received either
eprotirome 25, 50, or 100 mcg per day or placebo. Secondary outcomes were
changes in serum apo B, triglyceride, and Lp(a) concentrations. Safety
monitoring included assessments of potential adverse thyroid hormone-like
effects on the heart, bone, and pituitary.

The addition of eprotirome to statin treatment for 12 weeks resulted in
placebo-adjusted reductions in serum LDL-cholesterol concentrations of -15%,
-20%, and -26% with daily 25 mcg, 50 mcg and 100 mcg eprotirome, respectively.
Similar reductions were seen in serum apo B (-14%, -19%, and -24%),
triglycerides (-20%, -20%, and -37%), and Lp(a) (-17%, -22%, and -34%). These
effects on atherogenic lipid variables were similar in magnitude to those found
in a previous study where eprotirome was given as monotherapy, indicating a full
additive effect on top of statins. Eprotirome therapy was clinically very well
tolerated without adverse cardiac or bone effects. No change in serum Thyroid
Stimulating Hormone (TSH) or T3 was detected although the thyroxine (T4)
concentration decreased.

In eprotirome-treated patients, no significant changes were seen in body weight,
serum markers of bone turnover, heart rate, or blood pressure; no abnormal
cardiac rhythm or electrocardiography changes, including QTc interval, were
detected; and no pattern of symptoms suggesting clinical thyrotoxicosis or
hypothyroidism was observed. The frequency, pattern and intensity of adverse
events were similar in placebo and eprotirome-treated patients. Mild and
reversible increases in serum alanine aminotransferase were observed, and two
patients had confirmed ALT levels of more than three-fold the upper limit of the
normal range.

In conclusion, this randomized, placebo-controlled, double-blind trial has
demonstrated eprotirome's ability to further reduce serum LDL cholesterol levels
in statin-treated patients.  Eprotirome also possesses potent non-HDL
cholesterol, apo B, triglyceride and Lp(a) lowering properties. Eprotirome's
actions are exerted at doses where no adverse effects on the heart, bone, or
pituitary are evident. The therapeutic promise and safety of eprotirome as a
novel drug for treatment of dyslipidemia will need to be confirmed in
longer-term studies.  


For more information, please contact:

Jens D. Kristensen, Chief Medical Officer
Phone: +46 8 608 6005
E-mail: jens.kristensen@karobio.se 

Erika Söderberg Johnson, Chief Financial Officer
Phone: +46 8 608 6052
E-mail: erika.soderberg.johnson@karobio.se


Notes to editors

About Dyslipidemia and LDL cholesterol
The association of elevated circulating LDL cholesterol with increased
atherosclerotic cardiovascular disease risk is well established, as are the
reductions in both serum cholesterol and cardiovascular risk that occur with
statin therapy. However, the remarkable efficacy of statin therapy is limited by
patients failing to achieve their serum LDL cholesterol goals when treated with
these agents alone, and by patients suffering from side effects requiring dose
reduction or treatment discontinuation. Furthermore, statins show less efficacy
in lowering levels of other lipoproteins associated with increased
atherosclerotic vascular disease risk, i.e. hyper¬triglyceridemia and elevated
Lp(a). 

The cholesterol-lowering effect of thyroid hormone therapy in patients with
hypothyroidism was described already in 1930. LDL-cholesterol is the principal
lipoprotein fraction reduced, an action brought about by increased hepatic LDL
receptor gene expression. In rodents, thyroid hormone receptor agonists also
accelerate hepatic cholesterol disposal by increasing the HDL-receptor SR-B1,
elevating cholesterol 7a-hydroxylase activities and increasing fecal excretion
of cholesterol through bile acids.

Previous studies with naturally occurring thyroid hormone metabolites and
synthetic thyroid hormone receptor agonists have confirmed their cholesterol
lowering properties. However, development of some of these drugs has ceased due
to thyroid hormone-related adverse effects, such as effects on the heart with
D-thyroxine, and on bone with tiratricol. Karo Bio's aim with eprotirome has
been to develop a liver-selective thyroid hormone receptor agonist to avoid
these side effects.

About Karo Bio
Karo Bio is a drug discovery and development company specializing in
endocrinology and targeting nuclear receptors as target proteins for the
development of novel pharmaceuticals. The company has a project portfolio with
innovative molecules that primarily target dyslipidemia, diabetes, inflammation,
and women's health. In these areas, there are significant market opportunities
and a clear need for pharmaceuticals with new mechanisms of action. Karo Bio
develops compounds aimed at treating broad patient populations up to clinical
proof of concept before out-licensing. In therapeutic niche areas, Karo Bio has
the capacity to bring selected compounds into late stage clinical development
and, potentially, to the market. In addition to the proprietary projects, Karo
Bio has three strategic collaborations with international pharmaceutical
companies for development of innovative therapies for the treatment of common
diseases. Karo Bio is listed on NASDAQ OMX Stockholm since 1998 (Reuters:
KARO.ST).

This press release is also available online at: www.karobio.com and
www.newsroom.cision.com