The broad applicability of our antisense technology allows us to create promising drugs, such as the ocular and antiviral drugs under our preferred partner collaboration with GSK, in a variety of disease areas. We have successfully developed novel drugs designed to treat many different diseases. In therapeutic areas that are outside of our core areas of development, we have licensed our drugs to highly focused satellite companies that have the specific expertise and resources to continue developing the drugs. Together with our partners we continue to advance drugs in clinical development that are outside of our core therapeutic areas.
Plazomicin, formerly ACHN-490, is a next-generation aminoglycoside drug that Achaogen, Inc. 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 us.
Plazomicin has displayed broad-spectrum activity in animals against multi-drug resistant gram-negative bacteria that cause systemic infections, including E. coli, and 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 a Phase 2 study. In the Phase 2 study, Achaogen evaluated plazomicin compared to levofloxacin for the treatment of complicated urinary tract infections and acute kidney infections in adults. In this study, patients treated with plazomicin tolerated the drug well and patients demonstrated favorable activity of plazomicin as compared to levofloxacin.
Achaogen announced that it had reached agreement with the FDA to conduct the study under a SPA. Achaogen reported that the Phase 3 study is designed as a superiority study to evaluate the efficacy and safety of plazomicin compared with colistin in patients with bloodstream infections and nosocomial pneumonia caused by a class of MDR bacteria known as carbapenem-resistant enterobacteriaceae.
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 with Excaliard Pharmaceuticals, Inc. and exclusively licensed it to Excaliard for the local treatment of fibrotic diseases, including scarring. Fibrosis represents a significant and expanding area of unmet medical need where antisense drugs could offer a unique advantage as anti-fibrotic agents. In November 2011, Pfizer Inc. acquired Excaliard. Pfizer continues to evaluate EXC 001 in a Phase 2 program designed to provide information, including the optimization of the dose, for the design of the Phase 3 program for EXC 001.
iCo-007 is an antisense drug we designed to reduce c-Raf kinase. In preclinical studies, clinicians associated antisense inhibition of c-Raf kinase with a reduction in the formation and leakage of new blood vessels in the eye, suggesting inhibiting c-Raf kinase can help patients with diabetic macular edema and diabetic retinopathy. Diabetic retinopathy is one of the leading causes of blindness in people in the United States, and a high percentage of type 1 diabetics have evidence of retinopathy by age 20. Additionally, up to 21 percent of people with type 2 diabetes have retinopathy at the time of the first diagnosis of diabetes, and most will eventually develop some degree of retinopathy over time. We discovered iCo-007 and licensed it to iCo Therapeutics Inc., or 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 this study, a number of individuals exhibited a decrease of central macular edema compared to baseline using an analytical method called optical coherence tomography. iCo is currently evaluating iCo-007 in a Phase 2 study in patients with diabetic macular edema and plans to report data in 2014.
ATL1102 is an antisense drug that ATL is developing for the treatment of multiple sclerosis, or MS. ATL1102 inhibits CD49d, 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 MS. We licensed ATL1102 to ATL in December 2001 and in February 2008, ATL licensed ATL1102 to Teva. In 2008, ATL and Teva reported Phase 2a results of ATL1102 showing significantly reduced disease activity in patients with relapsing remitting MS. In 2010, Teva terminated its agreement with ATL and returned ATL1102 back to ATL. ATL is currently undertaking a chronic toxicology study in primates to support a potential Phase 2b trial of ATL1102 in patients with MS.
ISIS-GSK3Rx is an antisense drug we designed to an undisclosed target to treat a viral infection. ISIS-GSK3Rx is the third drug to enter development under our collaboration with GSK. We are eligible to receive milestone payments from GSK as ISIS-GSK3Rx advances in development, and we are responsible for developing the drug up to Phase 2 proof-of-concept, at which time GSK has the option to pay us a license fee and license ISIS-GSK3Rx from us. We are also eligible to receive double-digit royalties on sales of ISIS-GSK3Rx.
We are currently evaluating ISIS-GSK3Rx in a Phase 1/2 study in healthy volunteers and patients and expect to complete this study in 2014
ISIS-GSK4Rx is an antisense drug we designed to an undisclosed target to treat an ocular disease. We are developing ISIS-GSK4Rx as part of our collaboration with GSK. We are eligible to receive milestone payments from GSK as ISIS-GSK4Rx advances in development, and we are responsible for developing the drug up to Phase 2 proof-of-concept, at which time GSK has the option to pay us a license fee and license ISIS-GSK4Rx from us. We are also eligible to receive double-digit royalties on sales of ISIS-GSK4Rx
RG-101 is a preclinical drug that Regulus Therapeutics Inc., a company we co-founded focused on microRNA therapeutics, is developing. An oligonucleotide that inhibits microRNA, RG-101 is an anti-miR that targets microRNA-122, or miR-122. Researchers believe that miR-122 is essential for the replication of hepatitis C virus, or HCV, suggesting that an anti-miR-122 drug may reduce HCV infection and improve HCV-associated pathologies like fatty liver.
MicroRNAs are small RNA molecules that do not encode proteins, but instead work as natural antisense sequences that scientists believe regulate the expression of approximately one-third of all human genes.
Regulus currently plans to develop RG-101 as a key component of an HCV combination regimen for patients who have failed, or are intolerant of, the current standard of care and for specific patient populations, such as patients with HCV/HIV co-infections. Regulus is evaluating RG-101 in a Phase 1 study in healthy volunteers and in patients with HCV.
RG-012 is a preclinical drug candidate Regulus is developing, which is an anti-miR that targets microRNA-21, or miR-21. Regulus reports that subcutaneous administration of RG-012 significantly decreased the rate of renal fibrosis and increased the lifespan of mice treated with RG-012 up to 50 percent in a mouse model of Alport Syndrome. Alport Syndrome is a life-threatening disease in which patients experience progressive loss of kidney function.
Regulus currently plans to develop RG-012 to proof-of-concept. At that stage of development, Regulus’ partner Sanofi has an exclusive option to license. We are eligible to receive a portion of all milestone payments and royalties Regulus receives from Sanofi if Sanofi chooses to exercise its option to license RG-012 from Regulus and RG-012 advances in development.