Santaris Pharma A/S Advances New Cholesterol-Lowering Drug, SPC5001 Inhibiting Exciting New Target PCSK9, Into Phase 1 Clinical Trials for the Treatment of High Cholesterol

HOERSHOLM, Denmark and SAN DIEGO, May 4, 2011 /PRNewswire/ -- -- Phase 1 clinical study to assess safety and tolerability of SPC5001, a RNA-targeted drug inhibiting PCSK9, which is a protein involved in removing low-density lipoprotein cholesterol (LDL-C) or "bad" cholesterol from the bloodstream

-- In a study representing 147 million people, the World Health Organization recently reported that most patients with high cholesterol levels are not getting the treatment they need to reduce their risk of cardiovascular diseases such as heart attack and stroke

-- Data from preclinical studies showed that SPC5001 provided fast-acting, potent and long-lasting inhibition of PCSK9 and reductions in LDL-C by up to 74%

-- Developed using Santaris Pharma A/S Locked Nucleic Acid Drug Platform, SPC5001 is one of the drugs in the company's multi-faceted cardiometabolic program aimed at helping patients gain better control of their target cholesterol levels

Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, today announced that it has advanced SPC5001 into Phase 1 clinical trials for the treatment of high cholesterol. SPC5001 is a mRNA-targeted drug that inhibits the exciting new target, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a protein involved in removing low density lipoprotein cholesterol (LDL-C) or "bad" cholesterol from the bloodstream.

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

In a study representing 147 million people, the World Health Organization recently reported that most patients with high cholesterol levels are not getting the treatment they need to reduce their risk of cardiovascular diseases such as heart attack and stroke(1).

The randomized, dose-escalation, double-blind, placebo-controlled Phase 1 study will assess safety, tolerability, pharmacokinetics, and pharmacodynamics of SPC5001. The study aims to enroll 32 healthy volunteers and 8 patients with familial hypercholesterolemia who will be randomized to receive weekly subcutaneous injections of SPC5001 or placebo. Santaris Pharma A/S aims to first use SPC5001 in patients with familial hypercholesterolemia, a genetic disorder characterized by high cholesterol levels, specifically very high levels of LDL-C in the blood and often leads to early cardiovascular disease.

SPC5001 is one of the drugs from the company's multi-faceted cardiometabolic program aimed at helping patients achieve target cholesterol levels. Santaris Pharma A/S also plans to advance SPC4955 inhibiting apolipoprotein B (apoB) for the treatment of high cholesterol in the first half of 2011. In yet a third approach, in February 2011 Santaris Pharma A/S obtained an exclusive license from Massachusetts General Hospital for intellectual property related to the regulation of miR-33, an important microRNA that regulates high density lipoprotein (HDL) levels or "good" cholesterol.

"Having been recently discovered, PCSK9 is a high-value target for the treatment of high cholesterol and advancing SPC5001 into Phase 1 clinical studies is a significant step in potentially helping patients achieve their target cholesterol levels," said Arthur A. Levin, PhD, Vice President and Chief Development Officer of Santaris Pharma A/S. "Santaris Pharma is committed to helping patients better manage their cholesterol levels by moving multiple therapeutics from our cardiometabolic research programs such as SPC4955 and SPC5001 as a way to provide new treatment options for patients to better manage their high cholesterol levels and reduce the risks of cardiovascular disease."

In preclinical studies, SPC5001 provided fast-acting, potent and long-lasting inhibition of PCSK9 and provided reductions of mean LDL cholesterol by 50% in non-human primates with a sustained reduction of 74% in the highest responder. SPC5001 did not change HDL (high-density lipoprotein) levels or the "good" cholesterol in the blood(2). The preclinical data suggest that SPC5001 has the potential to provide patients with a new treatment option in managing their cholesterol levels.

In addition to its cardiometabolic programs, in September 2010, Santaris Pharma A/S successfully advanced miravirsen, a lead microRNA drug candidate targeting miR-122, into Phase 2 studies for the treatment of patients infected with the Hepatitis C virus.

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 potent single-stranded LNA-based drug candidates for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders.

With its partners, Santaris Pharma A/S also has a robust product pipeline consisting of mRNA and microRNA drug discovery and development collaborations. These include partnerships with Pfizer, Inc. (delivery of lead candidates against up to 20 targets), miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), GlaxoSmithKline (four viral disease drug candidates) and Enzon Pharmaceuticals (eight cancer targets successfully delivered - three are now in Phase 1 clinical studies).

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 all therapeutic uses of LNA. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit http://www.santaris.com for more information.

(1) http://www.who.int/mediacentre/news/notes/2011/cholesterol_20110201/en/

(2) Oral and poster presentation PCSK9 Conference, Locked Nucleic Acid antisense oligonucleotide inhibition of PCSK9, March 11, 2010