of the androgen receptor, including splice variants that have been implicated in promoting androgen resistance in
prostate cancer. Moreover, evidence was presented demonstrating that ISIS-AR-2.5
Rx
is effective in prostate
cancer models that display resistance to current standard of care prostate cancer treatments.
ISIS-AR-2.5
Rx
is part of our collaboration withAstraZeneca to discover and develop anti-cancer drugs.
AstraZeneca is currently evaluating ISIS-AR-2.5
Rx
in a Phase 1/2 study in patients withAR-related cancers and
plans to report data from this study in 2015.
Other Drugs in Development
The broad applicability of our antisense technology allows us to create promising drugs and 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, such as the ocular and
antiviral drugs we and GSK are developing under our preferred partner collaboration.
Plazomicin
—Plazomicin, formerlyACHN-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 is currently evaluating plazomicin in a Phase 3 study in patients with serious multi-drug resistant,
or MDR, gram-negative bacterial infections. The Phase 3 study is designed as a superiority study to evaluate the
efficacy and safety of plazomicin compared to colistin in patients with bloodstream infections and nosocomial
pneumonia caused by carbapenem-resistant Enterobacteriaceae, or CRE. Achaogen announced last year that it has
reached a special protocol assessment, or SPA, with the U.S. Food and DrugAdministration for this Phase 3
study.
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
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 in which
antisense drugs could offer a unique advantage as anti-fibrotic agents. In November 2011, Pfizer Inc. acquired
Excaliard. Pfizer has been evaluating 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.
ATL1102
—ATL1102 inhibits CD49d, a subunit of Very LateAntigen-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 licensedATL1102 toATL in December 2001. In 2008, ATL reported Phase 2a
results of ATL1102 showing significantly reduced disease activity in patients with relapsing remittingMS. In
2014, ATL completed a chronic toxicology study in primates to support a potential Phase 2b trial of ATL1102 in
patients withMS.
RG-101
—RG-101 is a preclinical drug that Regulus is developing. RG-101 is an anti-miR, antisense drug
designed to target microRNA-122, or miR-122. Researchers believe that miR-122 is essential for the replication
of HCV suggesting that an anti-miR-122 drug may reduce HCV infection and improve HCV-associated
pathologies like fatty liver.
MicroRNAs are small RNAmolecules 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.
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