Research Published in the New England Journal of Medicine Demonstrates Marked and Long-Lasting Antiviral Activity Against HCV

Research Published in the New England Journal of Medicine Demonstrates Marked
   and Long-Lasting Antiviral Activity Against HCV for Santaris Pharma A/S'
    Miravirsen, the First MicroRNA-Targeted Drug to Enter Clinical Trials

  PR Newswire

  HOERSHOLM, Denmark and SAN DIEGO, March 27, 2013

-- Final Phase 2a results show dose-dependent, prolonged antiviral activity in
Hepatitis C patients --

HOERSHOLM, Denmark and SAN DIEGO, March 27, 2013 /PRNewswire/ -- Santaris
Pharma A/S, a clinical-stage biopharmaceutical company focused on the
discovery and development of RNA-targeted therapies, today announced the
publication of study results online in the New England Journal of Medicine
(NEJM). The publication highlights the potential benefits of miravirsen, a
host-targeted, pan-HCV genotype anti-viral agent and the first
microRNA-targeted drug to enter clinical trials for the treatment of Hepatitis
C virus (HCV). In the study, miravirsen, given as a four-week monotherapy
treatment, provided robust dose-dependent antiviral activity with a mean
reduction of 2 to 3 logs from baseline in HCV RNA (log10 IU/mL). The effect
was sustained well beyond the end of therapy.

(Logo: http://photos.prnewswire.com/prnh/20100111/SPLOGO )

Clinical data from the Phase 2a study demonstrated the following:

  *Miravirsen was safe, well tolerated and provided prolonged antiviral
    activity well after the last dose of miravirsen monotherapy (x5 weekly
    injections)
  *There were no signs of viral resistance
  *Adverse events were infrequent, mild and did not lead to study drug
    discontinuation
  *There were no dose limiting toxicities or discontinuations due to adverse
    events
  *Miravirsen was associated with dose-dependent reductions in HCV RNA that
    were sustained well beyond the end of the four-week dosing period
  *Four out of nine patients treated at the highest dose (7 mg/kg) with
    miravirsen became HCV RNA undetectable with just five weekly doses of
    miravirsen monotherapy

"We are excited because the data show that miravirsen offers long-lasting
suppression of HCV RNA, a high barrier to viral resistance, a favorable
tolerability and dosing profile, a low propensity for drug interactions and a
very long duration of action. All of these properties suggest that
miravirsen's unique mechanism-of-action may offer a potential cure for
Hepatitis C patients, either in combination with other antiviral agents or as
a monotherapy," said Harry Janssen, M.D., Head of the Liver Clinic at Toronto
Western and Toronto General Hospital and lead author of the NEJM publication.
"Due to its ability to target the host factor miR-122, miravirsen has the
potential to change the way Hepatitis C is treated. This study is also the
first to prove that blocking microRNA can be effective in treating Hepatitis C
in humans without limiting side effects. This trial is a landmark study for
new therapeutic modalities in many other diseases where microRNA's play a
role, such as in cardiovascular disease, cancer and metabolic disorders."

Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug
Platform, miravirsen is an inhibitor of miR-122, a liver specific microRNA
that the Hepatitis C virus requires for replication. Miravirsen is designed to
recognize and sequester miR-122, making it unavailable to the Hepatitis C
virus. As a result, the replication of the virus is effectively inhibited and
the level of Hepatitis C virus is profoundly reduced.

"This is a seminal moment for the microRNA community as miravirsen is the
first microRNA targeted drug to show efficacy in clinical trials, and we are
honoured that such a prestigious journal as the New England Journal of
Medicine has published this work," said Henrik Stage, Chief Executive Officer
at Santaris Pharma A/S. "It's amazing to think that the journey from bench to
bedside has occurred over such a short span of time. Recall that human
microRNAs were only discovered in 2001, and miR-122's role in the HCV
lifecycle determined in 2005. Based on the published results, microRNA
targeted therapy has shown its potential to become a new important class of
drugs, and the LNA platform has demonstrated its role as the chemistry of
choice for RNA targeted therapies."

The randomized, double-blind, placebo-controlled, ascending multiple-dose
Phase 2a study assessed the safety and tolerability of miravirsen in
treatment-naive patients with chronic HCV genotype 1 infection. Patients were
enrolled sequentially to one of three cohorts (9 active: 3 placebo per cohort)
at doses of 3, 5 and 7 mg/kg. Miravirsen was given as a total of 5 weekly
subcutaneous injections over 29 days.

"These study results are the culmination of over 6 years of microRNA research
at Santaris Pharma A/S," said Michael R. Hodges, MD, Vice President and Chief
Medical Officer at Santaris Pharma A/S. "The results of this study highlight
miravirsen's exceptional high barrier to resistance , long duration of action
and good tolerability. Miravirsen would be especially suitable for treatment
of hard-to-treat patients, for example those patients who have already failed
treatment with pegylated-interferon and ribavirin combination or protease
inhibitor triple therapy." Dr. Hodges continued, "Longer treatment durations
of miravirsen are currently being tested in clinical trials in subjects who
have failed initial therapy for HCV infection."

About Hepatitis C Hepatitis C infection is a viral disease caused by the
Hepatitis C virus that leads to inflammation of the liver. The World Health
Organization estimates that approximately 3 percent of the world's population
have been infected with HCV and that some 170 million have chronic hepatitis C
and are at risk of developing liver cirrhosis and/or liver cancer[i].
Approximately 3-4 million Americans are chronically infected with an estimated
40,000 new infections per year[ii]. In Europe, there are about 4 million
carriers[i]. The current standard of care treatment for genotype 1 is a
protease inhibitor given with pegylated-interferona and ribavirin. This
triple combination is effective in about 70-80% of those treated[ii]. Patients
that are not effectively treated have an increased risk for the progression of
liver disease. By 2029, total annual medical costs in the United States for
people with Hepatitis C are expected to more than double, from $30 billion in
2009 to approximately $85 billion[iii].

About microRNAs MicroRNAs have emerged as an important class of small RNAs
encoded in the genome. They act to control the expression of sets of genes and
entire pathways and are thus thought of as master regulators of gene
expression. Recent studies have demonstrated that microRNAs are associated
with many disease processes. Because they are single molecular entities that
dictate the expression of fundamental regulatory pathways, microRNAs represent
potential drug targets for controlling many biologic and disease processes.

About Locked Nucleic Acid (LNA) Drug Platform The LNA Drug Platform and Drug
Discovery Engine developed by Santaris Pharma A/S combines the company's
proprietary LNA chemistry with its highly specialized and targeted drug
development capabilities to rapidly deliver LNA-based drug candidates against
RNA targets, both mRNA and microRNA, for a range of diseases including
cardiometabolic disorders, infectious and inflammatory diseases, cancer and
rare genetic disorders. LNA-based drugs are a promising new class of
therapeutics that are enabling scientists to develop drug candidates to work
through previously inaccessible clinical pathways. The LNA Drug Platform
overcomes the limitations of earlier antisense and siRNA technologies to
deliver potent single-stranded LNA-based drug candidates across a multitude of
disease states. The unique combination of small size and very high affinity
allows this new class of drugs candidates to potently and specifically inhibit
RNA targets in many different tissues without the need for complex delivery
vehicles. The most important features of LNA-based drugs include excellent
specificity providing optimal targeting; increased affinity to targets
providing improved potency; and favorable pharmacokinetic and
tissue-penetrating properties that allow systemic delivery of these drugs
without complex and potentially troublesome delivery vehicles.

About Santaris Pharma A/S Santaris Pharma A/S is a privately held
clinical-stage biopharmaceutical company focused on the discovery and
development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug
Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine
the company's proprietary LNA chemistry with its highly specialized and
targeted drug development capabilities to rapidly deliver potent
single-stranded LNA-based drug candidates across a multitude of disease
states. The company's research and development activities focus on infectious
diseases and cardiometabolic disorders, while partnerships with major
pharmaceutical companies include a range of therapeutic areas including
cancer, cardiovascular disease, infectious and inflammatory diseases, and rare
genetic disorders. The company has strategic partnerships with miRagen
Therapeutics, Shire plc., Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals.
As part of its broad patent estate, the company holds exclusive worldwide
rights to manufacture and sell products that comprise LNA as active ingredient
for studies performed with a view to obtaining marketing approval. Santaris
Pharma A/S, founded in 2003, is headquartered in Denmark with operations in
the United States. Please visit www.santaris.com for more information.

Santaris Pharma A/S® is a registered trademark of Santaris Pharma A/S.
Santaris™ and LNA-antimiR™ are trademarks of Santaris Pharma A/S.

[i] World Health Organization -
http://www.who.int/csr/disease/hepatitis/Hepc.pdf [ii] Jacobson IM. Telaprevir
for previously untreated chronic hepatitis C virus infection. NEJM
2011;364:2405-16[iii] Institute of Medicine of the National Academies.
Hepatitis and liver cancer: a national strategy for prevention and control of
hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at:
http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx
.

Website: http://www.santaris.com
Contact: Heather Platisha, Edelman, Office, (415) 486-3227,
heather.platisha@edelman.com
 
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