Infection by Hepatitis C virus is a significant and growing public health problem affecting as many as 170 million people worldwide.

The therapy currently used is ineffective in more than half of all patients, who progress to later stages of liver disease; for them the long-term prognosis is poor. Based on very promising pre-clinical data, some of which was published in Nature in 2008, Santaris Pharma has advanced its microRNA targeting drug, SPC3649, into human clinical trials. SPC3649 targets and inhibits the liver specific microRNA-122 which is required for the hepatitis C virus replication.

Unlike many other therapies for hepatitis C virus, SPC3649 works by altering the environment in the host liver cell to inhibit viral replication rather than inhibiting the virus itself. This subtle difference may have significant implications, as it may reduce the risk of the virus becoming resistant to therapy – a major concern with current therapies.

Western diet and life style combined with genetic traits have made metabolic diseases a growing health problem worldwide; cardiovascular diseases due to hyperlipidemia are the leading cause of death. In the US atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found in 80% to 90% of adults older than 30. Obesity and diabetes are at epidemic proportions in the US, Europe and many developing nations.

Santaris Pharma has several discovery programmes aimed at developing innovative LNA drugs in the metabolic disease space. The most advanced of these programmes targets the messengerRNA encoding the apolipoprotein B (apoB), a protein that constitutes an attractive pharmaceutical intervention point for lowering plasma cholesterol. Santaris Pharma’s apoB drug candidate SPC4955 is expected to reach the clinic in early 2010, offering all the advantages of the LNA technology, including high potency, rapid onset of activity, and a long lived pharmacologic response. We believe these properties create a significant competitive edge over therapies currently in development against apoB.

More than 10 million people worldwide are diagnosed with and more than 6 million people die from cancer each year. Santaris Pharma has continuously advanced its technology to the development of novel, effective cancer treatments in the hopes of improving patient life expectancy and quality of life.

Santaris Pharma a/s and its partner Enzon Pharmaceuticals have advanced three LNA drugs into clinical trials. Each of these LNA drugs targets messengerRNAs that are fundamental to cancer biology enabling them, if successful, to be used in the treatment of a diversity of solid and non-solid tumors.

SPC2996 is an inhibitor of Bcl-2, the overexpression of which enables cancer cells to evade body defenses that otherwise instruct malignant cells to terminate (apoptosis). SPC2996 has concluded two phase I/II trials in patients with Chronic Lymphocytic Leukemia (CLL) and is ready for further development in patients with solid tumors and cancers of the blood.

EZN2968 is an inhibitor of HIF-1α, a transcription factor that regulates a host of genes involved in crucial aspects of malignant cell behavior, such as angiogenesis, cell survival, glucose metabolism and invasion. EZN2968 is nearing the end of two phase I/II studies in patients with multiple tumor types and is expected to begin phase II trials later in 2009.

EZN3042 is an inhibitor of Survivin, which assists malignant cells in evading apoptosis and proliferates uncontrollably. EZN3042 recently commenced a phase I/II trial targeting solid tumors and lymphomas. In preclinical studies, EZN3042 inhibited Survivin expression and tumor growth. It also potentiated the antitumor activity of Taxol, an approved cancer therapeutic.

In addition to the three LNA drugs currently in the clinic, Santaris Pharma A/S is engaged in the discovery of LNA compounds targeting several other messengerRNA and microRNA targets that have been firmly linked to a broad spectrum of cancers.

Santaris Pharma and Enzon recently announced the identity of four of these drug discovery programmes which target HER3, beta-catenin, androgen receptor (AR) and phosphoinositide 3 –kinase (PI3K).    

• Quality of life of patients is often compromised by the lack or loss of autonomy   
• High level of pain and suffering for the patient and his/ her family   
• No existing effective cure   
• There are between 6000 and 8000 rare diseases   
• 75% of rare disease affect children   
• 30% of rare disease patients die before the age of 5   
• 80% of rare diseases have identified genetic origins