ARC1779 (TMA/TTP). Our aptamer product candidate, ARC1779, is a PEGylated aptamer consisting of 40 nucleotides that is administered intravenously. ARC1779 is designed to inhibit the platelet-binding function of a protein called von Willebrand Factor, or vWF. vWF plays a key role in the normal blood clotting process by mediating platelet activity. The body regulates vWF to maintain the normal balance between clotting and bleeding. The increase of vWF can cause disease characterized by excessive clotting, while a deficiency of vWF can cause disease characterized by excessive bleeding. We believe that ARC1779, with its potential to inhibit the function of vWF, could address significant, unmet medical needs in the treatment of patients who are suffering from blood disorders characterized by the increase of vWF.

We are developing ARC1779 to treat thrombotic microangiopathies, or TMA, which is a group of diseases caused by the increase of vWF. These diseases are characterized by the formation of excessive blood clots which block, or occlude, the arterial circulation and cause injury to key organs, including the brain, heart and kidneys. TMA includes the various forms of thrombotic thrombocytopenic purpura, or TTP, and hemolytic uremic syndrome, or HUS. TTP is a disease characterized by decreased platelet counts, or thrombocytopenia, the abnormal fragmentation of red blood cells, or microangiopathic hemolytic anemia, and small blood clots, or microthrombi. HUS is a disease characterized by thrombocytopenia, hemolytic anemia and kidney failure. There is no drug treatment specifically approved for patients with any form of TMA. Based on published case studies, we believe that the mortality rate for patients with TTP, which accounts for most of the patients with TMA, is up to approximately 20%.

In March 2007, we completed a Phase 1 clinical trial of ARC1779 in 47 healthy volunteers in which we observed no serious adverse events. In addition, we observed that vWF activity and platelet function were inhibited in a manner that correlated to the dose and concentration of ARC1779. We believe that the results of this trial demonstrate the mechanism of action of ARC1779 and support the continued development of this aptamer product candidate in patients with TMA. In January 2008, we commenced a Phase 2a clinical trial of ARC1779 in patients suffering from TTP. As of December 1, 2008, we had completed enrollment in the Phase 2a trial in TTP patients. In total, 21 patients were enrolled in the Phase 2a trial. On August 4, 2008, we submitted an IND for a Phase 2b trial of ARC1779 in patients suffering from TMA to the FDA, which included interim safety data from the Phase 2a trial. The IND became effective on September 4, 2008. Currently, one site in the United States is active and recruiting patients for the Phase 2b trial. We also have regulatory approval to conduct the Phase 2b trial in Canada and the United Kingdom and are waiting for regulatory approval in Austria, Switzerland and Italy. We estimate that a total of approximately 35 sites worldwide will be activated and recruiting patients during the course of the Phase 2b trial. Assuming timely enrollment, we believe that the recruitment phase of the study could last approximately 24 months.

ARC1779 for the treatment of TTP has received orphan designation in both the United States and the European Union.

ARC1779 (CEA). Carotid endarterectomy is a surgical procedure which removes an unwanted build-up of inflammatory cells, cholesterol and cellular debris known as plaque from the inner lining of the major arteries in the neck which supply blood to the brain. These vessels, known as the carotid arteries, can become narrowed by plaque, causing a reduction in blood flow to the brain. Blood clots can form on the surface of the plaque. Plaque or clots can then break loose and travel to the brain, blocking the blood flow to the brain and potentially causing permanent brain damage, stroke or death, if a large enough area of the brain is affected. If a clot or plaque blocks only a tiny artery in the brain, it may cause a transient ischemic attack, or TIA, also known as a ministroke. For patients experiencing a minor stroke or a TIA, a surgeon may recommend the surgical procedure known as carotid endarterectomy to remove plaque in the carotid arteries and help prevent a stroke. According to the AHRQ, more than 114,000 carotid endarterectomy procedures were performed in the United States in 2006.

We submitted the request for a CTA in the United Kingdom for the Phase 2a trial in September 2008. Regulatory approval was received in November 2008, and we expect to dose the first patient in this trial as early as the first quarter of 2009.

The Phase 2a trial will evaluate the safety and efficacy of ARC1779 in patients undergoing carotid endarterectomy. The primary objectives of the trial will be to measure the effectiveness of ARC1779 in reducing the number of small blood clots which form immediately following the operation and then flow to the brain, and assess the safety of ARC1779 by measuring the amount of bleeding that occurs at the site of surgery during the operation. This trial is expected to be a randomized, double-blind, placebo controlled single dose study in up to 100 patients undergoing elective carotid endarterectomy. Other secondary objectives expected to be assessed include the effect of ARC1779 administration on reducing the brain damage caused by the small blood clots which form immediately following the operation. The study will also assess the safety and tolerability and the pharmacokinetic and pharmacodynamic parameters of ARC1779.

REG1 (ACS - PCI / CABG) See http://www.regadobiosciences.com/pipeline-clinical/pipeline.htm for more details.

REG2 (VTE Prophylaxis) See http://www.regadobiosciences.com/pipeline-clinical/pipeline.htm for more details.

REG3 (Antiplatelet Therapy) See http://www.regadobiosciences.com/pipeline-clinical/pipeline.htm for more details.

NU172 (CABG/PCI). Nuvelo, Inc. is developing NU172 as an anticoagulant for use in acute cardiovascular surgeries. NU172 is being tested as a fast-acting, short half-life anti-coagulant. NU172 targets thrombin, which is a protein required for blood clotting. NU172 is designed to be administered by intravenous infusion during an acute cardiovascular surgical procedure to prevent the formation of harmful blood clots. The resulting period of anticoagulation is designed to be maintained until the infusion is stopped. With its rapid offset of action, NU172 is designed to return the body to its normal state of hemostasis shortly after the cessation of the infusion.

Nuvelo completed Phase 1a and 1b clinical trials with NU172. In August 2008, Nuvelo announced the results of the Phase 1b trial, which demonstrated that NU172 produced and maintained dose-dependent increases in anticoagulation with a rapid return toward baseline after the infusion ended with a favorable safety profile. Nuvelo has announced that it plans to commence a Phase 2 study evaluating NU172 in the fourth quarter of 2008 or the first quarter of 2009.

Hemophilia. Hemophilia is a family of rare bleeding disorders that impairs the body’s ability to control the normal blood clotting process. Persons with hemophilia have low levels, or a complete absence, of specific proteins, called factors, in their blood that work with platelets to help the blood clot. Proper clotting of blood allows a blood vessel to heal after an injury and prevents excessive bleeding. In hemophiliacs, deficiency or absence of normal clotting factors can cause abnormally long bleeding after an injury or surgery or spontaneous bleeding into the joints and muscles. According to the Centers for Disease Control and Prevention, hemophilia afflicts approximately 18,000 people in the United States. According to EvaluatePharma, drugs for the treatment of hemophilia in major pharmaceutical markets generated approximately $4.5 billion in sales in 2006. There is currently no cure for hemophilia. Currently approved treatments for hemophilia address the symptoms of hemophilia rather than its cause and rely largely on drugs that replace the function of missing clotting factors. We believe that an aptamer for treatment of hemophilia may meet the criteria for orphan drug designation in the United States and the European Union.

We believe that there is an unmet medical need in hemophilia, which represents a significant opportunity for drug discovery. We are researching aptamers that may bind to and inhibit the function of certain proteins that we believe may play a role in hemophilia.

Sickle Cell Disease. Sickle cell disease is a chronic and debilitating genetic blood disorder, primarily affecting individuals of African descent, resulting in a variety of disease complications and a significantly shortened lifespan in the majority of patients. Sickle cell disease is caused by the presence of an abnormal form of hemoglobin, the protein inside red blood cells that is responsible for carrying oxygen, which leads to abnormally shaped red blood cells. According to the National Heart Lung and Blood Institute, sickle cell disease affects about 70,000 people in the United States. According to the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project, sickle cell disease accounted for approximately 85,000 hospitalizations in the United States in 2005. The only approved drug for the treatment of sickle cell disease is hydroxyurea, a drug primarily used as a cancer chemotherapeutic agent that is prescribed to treat the symptoms of only the most severely ill patients due to its potentially serious side effects. We believe that an aptamer for treatment of sickle cell disease may meet the criteria for orphan drug designation in the United States and the European Union.

We believe that there is an unmet medical need in sickle cell disease, which represents a significant opportunity for drug discovery. We are researching aptamers that may bind to and inhibit the function of certain proteins that we believe may play a role in sickle cell disease.

AS1411 (AML). Antisoma plc is developing an aptamer it calls AS1411. AS1411 binds to a protein called nucleolin, which is found on the surface of cancer cells. When AS1411 binds to nucleolin, it is internalized and has been shown to kill cancer cells in a range of animal models.

Antisoma studied AS1411 in a Phase 1 clinical trial that concluded in October 2006. In total, the study enrolled 30 patients. The data presented by Antisoma at the European Society of Medical Oncology meeting in October 2006 showed that signs of anti-cancer activity were observed in patients with renal cell carcinoma. Twelve of the patients in the Phase 1 trial had this type of cancer. Of these patients, two showed a complete or partial response, both with tumor shrinkage, and seven additional patients experienced disease stabilization for two months or longer. Furthermore, no serious adverse events related to drug administration were reported at any dose level.

In August 2007, Antisoma commenced a Phase 2 clinical trial with AS1411 in patients with relapsed and refractory acute myeloid leukemia, or AML. In July 2008, Antisoma announced initial results from this clinical trial. In total, 33 patients were randomly assigned to be treated with either 10 mg/kg/day of AS1411 plus an approved drug known as cytarabine, or with cytarabine alone. According to Antisoma, the addition of AS1411 to cytarabine at this dose was well tolerated. Antisoma reported activity data from 16 patients. Among 11 patients who received AS1411 plus cytarabine, one had a complete response, or CR, and one had a complete response with incomplete recovery of platelet counts, or CRP, while a third patient had a response but had cancer cells remaining. Among five patients who received cytarabine alone, none had a CR or CRP. Patients who did not respond to cytarabine alone could be crossed over to receive AS1411 plus cytarabine; two of the first five patients crossed over and one showed a 90% reduction in cancer cell count after treatment with the combination.

AS1411 (Renal Cell). Antisoma plc is developing an aptamer it calls AS1411. AS1411 binds to a protein called nucleolin, which is found on the surface of cancer cells. When AS1411 binds to nucleolin, it is internalized and has been shown to kill cancer cells in a range of animal models.

Antisoma studied AS1411 in a Phase 1 clinical trial that concluded in October 2006. In total, the study enrolled 30 patients. The data presented by Antisoma at the European Society of Medical Oncology meeting in October 2006 showed that signs of anti-cancer activity were observed in patients with renal cell carcinoma. Twelve of the patients in the Phase 1 trial had this type of cancer. Of these patients, two showed a complete or partial response, both with tumor shrinkage, and seven additional patients experienced disease stabilization for two months or longer. Furthermore, no serious adverse events related to drug administration were reported at any dose level.

In September 2008, Antisoma announced that it commenced a separate Phase 2 clinical trial of AS1411 in patients with renal cell carcinoma. In December 2008, Antisoma announced initial results from this clinical trial. In total, 28 patients who were assigned to be treated with either 10 mg/kg/day of AS1411 plus an approved drug known as cytarabine, or with cytarabine alone, were evaluated for efficacy. According to Antisoma, the addition of AS1411 to cytarabine at this dose was well tolerated. Among the patients who received AS1411 plus cytarabine, two had a complete response, or CR, and one had a complete response with incomplete recovery of platelet counts, or CRP. Among five patients who received cytarabine alone, none had a CR or CRP. Patients who did not respond to cytarabine alone could be crossed over to receive AS1411 plus cytarabine; one of the first three patients crossed over and one showed a 90% reduction in cancer cell count after treatment with the combination.

E10030 (AMD/DR). Ophthotech is developing E-10030, an aptamer directed against platelet-derived growth factor-B (PDGF-B) for the potential treatment of wet AMD.

Neovascular, or wet AMD, results in sudden and often substantial loss of central vision and is responsible for the majority of cases of severe loss of visual acuity in this disease. Wet AMD results when abnormal blood vessels proliferate under and/or within the retina. These blood vessels leak blood and fluid into the retina, which results in vision loss. It is believed that proteins including platelet-derived growth factor-B, or PDGF-B, and vascular endothelial growth factor, or VEGF, are key mediators of the excessive and abnormal blood vessel growth. Therefore, combination therapy in wet AMD with anti-VEGF and anti-PDGF agents could represent a new therapy for treating wet AMD.

E10030 is an aptamer directed against PDGF-B. Pharmacology studies indicate that E10030 binds to PDGF-B with high specificity and affinity and inhibits the functions of PDGF-B. In preclinical studies, E10030 demonstrated the potential to regress neovascularization when used in combination with a VEGF inhibitor. In February 2008, Ophthotech commenced a Phase 1 clinical trial of E10030 for the treatment of wet AMD. The Phase 1 trial will assess the safety and tolerability of E10030 in combination with an anti- VEGF agent. Ophthotech expects that this clinical trial will enroll up to a maximum of 36 patients.

ARC1905 (AMD). ARC1905 inhibits C5, a central component of the complement cascade, which plays multiple roles in innate immunity and inflammatory diseases. Mounting evidence suggests an important link between complement and the development of age-related macular degeneration (AMD). Ophthotech is also developing an aptamer it calls ARC1905 for the potential treatment of wet AMD and non-neovascular or dry AMD.

Dry AMD, is characterized by slow degeneration of the light-sensitive photoreceptor cells in the eye which leads to gradually blurring of the central vision in the affected eye. The deterioration of vision is usually gradual over a period of years but is considered irreversible and can result in profound vision loss. Additionally, dry AMD can progress to the wet form of the disease.

Ophthotech has stated that it believes that both the wet and dry forms of AMD are primarily the result of an inflammatory process. ARC1905 is an aptamer that targets and suppresses a protein known as C5 which plays multiple roles in the body’s immune system and inflammatory responses. In October 2008, Ophthotech commenced a Phase 1 clinical trial of ARC1905. This Phase 1 clinical trial will assess the safety and tolerability of ARC1905 in combination with an anti-VEGF agent.