Regulus Therapeutics Inc. today announced the establishment of a new
collaboration with GlaxoSmithKline (GSK) to develop and commercialize
microRNA therapeutics targeting microRNA-122 in all fields with
Hepatitis C Viral infection (HCV) as the lead indication. Under the
terms of the new collaboration, Regulus will receive additional upfront
and early-stage milestone payments with the potential to earn more than
$150 million in miR-122-related combined payments, and tiered royalties
up to double digits on worldwide sales of products.
"This new collaboration with GSK demonstrates the clear scientific
leadership that Regulus has established in advancing a whole new
frontier of pharmaceutical research. microRNA therapeutics target the
pathways of human diseases, not just single disease targets, and hold
considerable promise as novel therapies across a broad range of unmet
medical needs,” said Kleanthis G. Xanthopoulos, Ph.D., President and
Chief Executive Officer of Regulus. "It also further validates Regulus’
microRNA product platform built on fundamental biology of human diseases
and intellectual property, and also extends the therapeutic scope of our
existing collaboration formed with GSK in 2008. Furthermore, the funding
from this alliance supports Regulus’ efforts in advancing high impact,
novel medicines based on microRNA biology to patients.”
The collaboration provides GSK with access to Regulus’ comprehensive and
robust intellectual property estate. Regulus exclusively controls patent
rights covering miR-122 antagonists and their use as HCV therapeutics in
the United States, Europe, and Japan, including but not limited to the
patent families which encompass: the ‘Sarnow’ patent pertaining to the
method of use of anti-miR-122 to inhibit HCV replication, the ‘Esau’
patent application claiming the use of anti-miRs targeting miR-122 as
inhibitory agents, the ‘Tuschl III’ patent claiming composition of
matter for miR-122 and complementary oligonucleotides, and the
‘Manoharan’ patent claiming antagomirs, including antagomirs targeting
miR-122.
miR-122 is a liver-expressed microRNA that has been shown to be a
critical endogenous "host factor” for the replication of HCV, and
anti-miRs targeting miR-122 have been shown to block HCV infection
(Jopling et al. (2005) Science 309, 1577-81). In earlier
work, scientists at Alnylam and Isis demonstrated the ability to
antagonize miR-122 in vivo using chemically modified
single-stranded anti-miR oligonucleotides. Further, work by Regulus
scientists and collaborators showed that inhibiting miR-122 results in
significant inhibition of HCV replication in human liver cells,
suggesting that antagonism of miR-122 may comprise a novel "host factor”
therapeutic strategy. Regulus scientists have shown in multiple
preclinical studies a robust HCV antiviral effect following inhibition
of miR-122. Regulus plans to identify a clinical development candidate
in the second half of 2010 and file an investigational new drug (IND)
application in 2011.
About microRNAs
The discovery of microRNA in humans is one of the most exciting
scientific breakthroughs in the last decade. microRNAs are small RNA
molecules, typically 20 to 25 nucleotides in length, that do not encode
proteins but instead regulate gene expression. Nearly 700 microRNAs have
been identified in the human genome, and more than one-third of all
human genes are believed to be regulated by microRNAs. As a single
microRNA can regulate entire networks of genes, these new molecules are
considered the master regulators of the genome. microRNAs have been
shown to play an integral role in numerous biological processes
including the immune response, cell-cycle control, metabolism, viral
replication, stem cell differentiation and human development. Many
microRNAs are conserved across multiple species indicating the
evolutionary importance of these molecules as modulators of critical
biological pathways. Indeed, microRNA expression or function has been
shown to be significantly altered in many disease states, including
cancer, heart failure and viral infections. Targeting microRNAs opens
the possibility of a novel class of therapeutics and a unique approach
to treating disease by modulating entire biological pathways.
About Hepatitis C Virus (HCV)
HCV infection is a disease with an estimated prevalence of 170 million
patients worldwide, with more than 3 million patients in the United
States. HCV shows significant genetic variation in worldwide populations
due to its frequent rates of mutation and rapid evolution. There are six
genotypes of HCV, with several subtypes within each genotype, which vary
in prevalence across the different regions of the world. The response to
treatment varies from individual to individual underscoring the
inadequacy of existing therapies and highlights the need for combination
therapies that not only target the virus but endogenous "host factors”
as well. Strategies that include the Regulus miR-122 antagonist as part
of emerging combination therapies to shorten duration of treatment and
interferon use, improve the safety profile and sustained virologic
response (SVR), increase the barrier to drug resistance, and address
difficult-to-treat genotypes hold significant potential to expand the
limited therapies available to physicians treating HCV patients.
About Regulus Therapeutics Inc.
Regulus Therapeutics is a biopharmaceutical company leading the
discovery and development of innovative new medicines based on
microRNAs. Regulus is targeting microRNAs as a new class of therapeutics
by working with a broad network of academic collaborators and leveraging
oligonucleotide drug discovery and development expertise from its
founding companies Alnylam Pharmaceuticals (Nasdaq:ALNY) and Isis
Pharmaceuticals (Nasdaq:ISIS). Regulus is advancing microRNA
therapeutics towards the clinic in several areas including hepatitis C
infection, cardiovascular disease, fibrosis, oncology,
immuno-inflammatory diseases, and metabolic diseases. Regulus’
intellectual property estate contains both the fundamental and core
patents in the field as well as over 600 patents and more than 300
pending patent applications pertaining primarily to chemical
modifications of oligonucleotides targeting microRNAs for therapeutic
applications. In 2008, Regulus entered into a major alliance with
GlaxoSmithKline to discover and develop microRNA therapeutics for
immuno-inflammatory diseases. For more information, visit www.regulusrx.com.
Forward-Looking Statements
This press release includes forward-looking statements regarding the
future therapeutic and commercial potential of Regulus’, Alnylam’s, and
Isis’ business plans, technologies and intellectual property related to
microRNA therapeutics being discovered and developed by Regulus,
including statements regarding expectations around the relationship
between GSK and Regulus. Any statement describing Regulus’, Alnylam’s,
and Isis’ goals, expectations, financial or other projections,
intentions or beliefs is a forward-looking statement and should be
considered an at-risk statement, including those statements that are
described as such parties’ goals. Such statements are subject to certain
risks and uncertainties, particularly those inherent in the process of
discovering, developing and commercializing drugs that are safe and
effective for use as human therapeutics, and in the endeavor of building
a business around such products. Such parties’ forward-looking
statements also involve assumptions that, if they never materialize or
prove correct, could cause their results to differ materially from those
expressed or implied by such forward-looking statements. Although these
forward-looking statements reflect the good faith judgment of the
management of each such party, these statements are based only on facts
and factors currently known by Regulus’, Alnylam’s, and Isis’ management
as the case may be. As a result, you are cautioned not to rely on these
forward-looking statements. These and other risks concerning Regulus’,
Alnylam’s, and Isis’ programs are described in additional detail in
Alnylam’s and Isis’ annual reports on Form 10-K for the year ended
December 31, 2008, and their most recent quarterly reports on Form 10-Q
which are on file with the SEC. Copies of these and other documents are
available from Alnylam or Isis.
