Inflammation and Other Diseases

The broad applicability of our antisense technology allows us to create promising drugs in a variety of disease areas, many of which are underserved with current treatment options.

We have been successful in developing novel drugs and licensing them to highly focused satellite companies that have the specific expertise and resources to continue developing these drugs. Together with our partners we continue to advance new drugs into development and move antisense drugs into clinical studies that are outside of our core therapeutic areas. For instance, our partner, Excaliard, presented data from three Phase 2 studies demonstrating that EXC 001 reduced scarring in patients.

• Vitravene^® (CMV Retinitis)
• Alicaforsen (Ulcerative Colitis, Pouchitis)
• Plazomicin (Severe Bacterial Infection)
• ATL1102 (Multiple Sclerosis)
• EXC 001 (Local Fibrosis)
• iCo-007 (Diabetic Macular Edema, Diabetic Retinopathy)

Vitravene^®

Vitravene, approved by the FDA in 1998, is an antisense drug that we discovered and developed to treat cytomegalovirus, or CMV retinitis, in AIDS patients. Novartis Ophthalmics AG, our worldwide distribution partner for this drug, launched Vitravene in November 1998. New anti-HIV drugs, particularly protease inhibitors and combination treatment regimens, have prolonged survival in HIV-infected individuals. This has resulted in a decline in mortality from AIDS, accompanied by a decline in the incidence of many opportunistic infections, including CMV retinitis. As a result, Novartis no longer markets Vitravene. Vitravene demonstrates our ability to meet FDA and European regulatory requirements for safety and efficacy, and for the commercial manufacture of antisense drugs.

Alicaforsen

Alicaforsen, now under license to Atlantic Pharmaceuticals Limited, is an antisense drug that targets intercellular adhesion molecule 1, or ICAM-1. ICAM-1 is over-expressed in a wide variety of inflammatory disorders, including ulcerative colitis and pouchitis. Ulcerative colitis, or UC, is an inflammatory bowel disease, or IBD, of the colon, a part of the large intestine, and pouchitis is an inflammation of the surgically constructed internal pouch created in UC patients who have had their diseased colons removed. In 2007, we licensed alicaforsen to Atlantic Pharmaceuticals for pouchitis, UC and other inflammatory diseases. The FDA and European Medicines Agency, or EMEA, have since granted alicaforsen Orphan Drug Designation for the treatment of pouchitis in the United States and Europe respectively. Atlantic Pharmaceuticals currently supplies alicaforsen in response to physicians' requests under international Named Patient Supply regulations for patients with IBD.

Plazomicin

Plazomicin (formerly ACHN-490) is a next-generation aminoglycoside drug that Achaogen is developing for the treatment of multi-drug resistant gram-negative bacterial infections. Aminoglycosides are a group of antibiotics that inhibit bacterial protein synthesis and that clinicians use to treat serious bacterial infections. Achaogen discovered plazomicin based on technology licensed from Isis. Plazomicin has displayed broad-spectrum activity in animals against multi-drug resistant gram-negative bacteria that cause systemic infections, including E. coli, as well as against methicillin-resistant staphylococcus aureus, or MRSA. In preclinical studies, plazomicin demonstrated an acceptable safety profile and the potential for once-daily dosing. Achaogen has completed a Phase 1 study of plazomicin in healthy volunteers, and is currently enrolling patients in a Phase 2 study.

ATL1102

ATL1102 is an antisense inhibitor of CD49d, which is a subunit of Very Late Antigen-4, or VLA-4. Studies in animal models have demonstrated that inhibiting VLA-4 positively affects a number of inflammatory diseases, including multiple sclerosis, or MS.

We licensed ATL1102 to Antisense Therapeutics Limited in December 2001. In 2008, ATL reported Phase 2a results of ATL1102 showing significantly reduced disease activity in patients with relapsing remitting MS.

EXC 001

EXC 001 is an antisense drug that targets connective tissue growth factor, or CTGF, a growth factor that is over-expressed in damaged skin or tissue following a traumatic event. We co-discovered EXC 001 and licensed it to Excaliard for the local treatment of fibrotic diseases, including scarring. In November 2011, Pfizer Inc. acquired Excaliard and will continue to develop EXC 001. Fibrosis represents a significant and expanding area of unmet medical need in which antisense drugs could offer a unique advantage for anti-fibrotic agents.

Excaliard reported the successful completion of three Phase 2 studies. In one Phase 2 study, treatment with EXC 001 produced a significant improvement in the appearance of scarring in patients who had revision surgery for excessive scarring. In another Phase 2 study, treatment with EXC 001 also reduced the severity of fine line scars and accelerated resolution of scarring compared to placebo. In a third Phase 2 study, treatment with EXC 001 produced a dose-dependent reduction in CTGF and inhibition of CTGF-induced collagen and other pro-fibrotic genes. In all three studies, Excaliard reported that treatment with EXC 001 produced statistically significant reductions in scar severity compared to placebo and subjects tolerated EXC 001 well with no important drug related adverse effects observed. EXC 001 is currently being evaluated in a Phase 2b study in patients following breast scar revision surgery.

iCo-007

iCo-007 is an antisense drug that targets c-Raf kinase. In preclinical studies, antisense inhibition of c-Raf kinase was associated with a reduction in the formation and leakage of new blood vessels in the eye, suggesting inhibiting c-Raf kinase can improve treatment for both diabetic macular edema and diabetic retinopathy. Diabetic retinopathy is one of the leading causes of blindness in people in the U.S., and nearly 100 percent of type 1 diabetics by age 20 have evidence of retinopathy. Additionally up to 21 percent of people with type 2 diabetes have retinopathy when they are first diagnosed with diabetes, and most will eventually develop some degree of retinopathy. We discovered iCo-007 and licensed it to iCo for the treatment of various eye diseases that occur as complications of diabetes.

In May 2010, investigators evaluating iCo-007 in patients with diffuse Diabetic Macular Edema presented positive results from the Phase 1 study showing that subjects tolerated iCo-007 well. In August 2011, iCo initiated a Phase 2 study on iCo-007 in patients with Diabetic Macular Edema.