In February 2015, Regulus reported data from the Phase 1/2 study of RG-101 in patients with HCV. Regulus
reported results from this study demonstrating that treatment with a single subcutaneous dose of 2 mg/kg or
4 mg/kg of RG-101 as monotherapy resulted in significant and sustained reductions in HCVRNA in a varied
group of patients, including difficult to treat genotypes and patients who experienced viral relapse after a prior
interferon-containing regimen. Additionally, RG-101 was well tolerated and has demonstrated a favorable
pharmacokinetic profile to date, which Regulus believes may allowRG-101 to be combined with oral
direct-acting antiviral agents to treat HCV. Regulus expects to initiate two Phase 2 studies evaluating RG-101 as
a single agent and in combination with direct acting antivirals in patients with HCV in 2015.
ISIS-HBV
Rx
—ISIS-HBV
Rx
, formerly ISIS-GSK3
Rx
, is an antisense drug we designed to reduce the
production of viral proteins associated with hepatitis B virus, or HBV, infection and replication. Hepatitis B virus
infection is a serious health problem that can lead to significant and potentially fatal health conditions. Chronic
HBV infection is one of the most common persistent viral infections in the world. Currently available therapies,
including oral antiviral agents or injectable interferons, do not clear HBV and do not effectively clear HBV
antigens from these patients. As a result, patients are unable to fully control HBV infection and achieve sustained
disease remission. Many of these patients are at elevated risk for severe liver complications such as cirrhosis and
primary liver cancer.
In preclinical studies, an antisense compound targeting HBV produced dose-dependent reductions of
HBV-associated antigens, including hepatitis B surface antigen, which is present in both acute and chronic
infections and is associated with a poor prognosis in patients with chronic HBV infection. In addition, other
measures of viral infection were reduced in both the liver and serum following treatment with the ISIS-HBV
Rx
.
We have completed a Phase 1 study of ISIS-HBV
Rx
in healthy volunteers and plan to initiate a Phase 2 study in
patients with HBV in 2015.
Preclinical Development
The table below lists our preclinical drugs for a number of different diseases.
Drug
Indication
Partner
ISIS-GSK4-L
Rx
Ocular Disease
GSK
ISIS-GSK6-L
Rx
Antiviral
GSK
Antisense Technology
Our core technology platform can support multiple target-based antisense research programs without
significantly increasing costs. We can design our antisense drugs to target a broad range of diseases, efficiently
producing a proprietary portfolio of drugs that can interrupt the production of disease-causing proteins or reduce
harmful RNAs without disrupting other proteins that are necessary for the body’s normal functions. We are
currently pursuing antisense drug discovery programs focused on various severe and rare, cardiovascular,
neurologic and metabolic diseases and cancer.
Genes contain the information necessary to produce proteins. Agene is made up of nucleoside bases:
Adenine, Thymine, Guanine, and Cytosine, commonly known as A, T, G and C, which are linked together to
form a two-stranded structure that resembles a twisted ladder, known as deoxyribonucleic acid, or DNA. The
nucleotides on one side of the ladder bind weakly to complementary nucleotides on the other strand according to
specific rules; for example, Apairs with T and G pairs with C, creating the ladder’s rungs. Scientists call this
highly specific nucleotide pairing hybridization. The sequence or order of these nucleotides establishes the cell’s
recipes for making proteins. Each protein’s instructions reside in a corresponding segment of DNAknown as a
gene.
When a cell transcribes information from a DNAgene into mRNA the two complementary strands of the
DNApartly uncoil. One strand acts as a template and information stored in the DNA strand is copied into a
complementary mRNA. mRNA then carries the information to cellular structures called ribosomes, the cell’s
factories for manufacturing proteins. The ribosome reads the encoded information, the mRNA’s nucleotide
sequence, and in doing so, strings together amino acids to form a specific protein. This process is called
translation. We primarily use our antisense technology to interrupt the cell’s protein production process by
preventing the RNA instructions from reaching the ribosome, thus inhibiting the synthesis of the protein. The
mRNA sequence of nucleotides that carries the information for protein production is called the ’sense’ strand.
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