Flash Info Biotech

LONDON & PHILADELPHIA & CARLSBAD, Calif.–(BUSINESS WIRE)–GlaxoSmithKline (GSK) and Regulus Therapeutics LLC (Regulus) today
announced a worldwide strategic alliance to discover, develop and market
novel microRNA-targeted therapeutics to treat inflammatory diseases such
as rheumatoid arthritis and inflammatory bowel disease. Regulus is a
joint venture between Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and
Isis Pharmaceuticals, Inc. (Nasdaq: ISIS).

The alliance leverages Regulus’ unique
expertise and intellectual property position in the discovery and
development of microRNA-targeted therapeutics and provides GSK with an
option to license product candidates directed at four different microRNA
targets with relevance in inflammatory disease. Regulus will be
responsible for the discovery and development of the microRNA
antagonists through completion of clinical proof of concept, unless GSK
chooses to exercise its option earlier. After exercise of the option,
GSK will have an exclusive license to drugs developed under each program
by Regulus for the relevant microRNA target for further development and
commercialization on a worldwide basis. Regulus will have the right to
further develop and commercialize any microRNA therapeutics which GSK
chooses not to develop or commercialize.

Regulus will receive $20 million in upfront payments from GSK, including
a $15 million option fee and a $5 million note (guaranteed by Isis and
Alnylam) that will convert into Regulus common stock in the future under
certain specified circumstances. Regulus could also be eligible to
receive up to $144.5 million in development, regulatory and sales
milestone payments for each of the four microRNA-targeted therapeutics
discovered and developed as part of the alliance. In addition to the
potential of nearly $600 million Regulus could receive in option,
license and milestone payments, Regulus would also receive tiered
royalties up to double digits on worldwide sales of products resulting
from the alliance.

“We are focused on finding innovative
medicines through both internal efforts and by ‘virtualizing’ a portion
of the inflammatory diseases pipeline. We are very excited to be working
with Regulus and exploring the therapeutic opportunities in inflammation
offered by targeting microRNAs, an exciting new area of biology,”
said Jose Carlos Gutierrez-Ramos, Ph.D., Senior Vice President and head
of the Immuno-Inflammation Center of Excellence for Drug Discovery of
GSK. “When associated with an aberrant
inflammatory response, microRNAs represent disease targets whose
therapeutic modulation could revolutionize the way we treat immune
diseases and provide benefits not readily achievable with today’s
medicines.”

“GSK is an outstanding partner for Regulus,
and we look forward to expanding our efforts in inflammation where a new
class of therapeutics could offer novel options to treat disease,”
said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive
Officer of Regulus. “microRNA therapeutics
represent an exciting new frontier for pharmaceutical research, opening
many opportunities including those present in inflammation and immune
diseases. As a leading microRNA therapeutics company, Regulus has the
expertise and access to proprietary antisense technologies, which
provide the tools and potential to quickly move therapeutic programs
toward the clinic. Through its relationship with Alnylam and Isis,
Regulus also has a vast patent estate in microRNAs.”

About microRNAs

microRNAs are a recently discovered class of genetically encoded small
RNAs, approximately 20 nucleotides in length, and are believed to
regulate the expression of a large number of human genes. microRNA
therapeutics represent a new approach for the treatment of a wide range
of human diseases. The inappropriate absence or presence of specific
microRNAs in various cells has been shown to be associated with specific
human diseases including cancer, viral infection, and metabolic
disorders. Targeting microRNAs with novel therapeutic agents could
result in high-impact and broadly acting treatments for human diseases.

About Regulus Therapeutics LLC

Regulus is a biopharmaceutical company formed to discover, develop and
commercialize microRNA therapeutics. Regulus was founded in late 2007 as
a joint venture between Alnylam Pharmaceuticals, a leader in RNAi
therapeutics, and Isis Pharmaceuticals, a leader in antisense
technologies and therapeutics. Isis and Alnylam scientists and
collaborators were the first to discover microRNA antagonist strategies
that work in vivo in animal studies (Krutzfeldt et al. Nature
438, 685-689 (2005); Esau et al. Cell Metab., 3,
87-98 (2006)). Isis and Alnylam have also created and consolidated key
intellectual property for the development and commercialization of
microRNA therapeutics. Regulus maintains facilities in Carlsbad,
California. For more information, visit www.regulusrx.com.

About Alnylam Pharmaceuticals, Inc.

Alnylam is a biopharmaceutical company developing novel therapeutics
based on RNA interference, or RNAi. The company is applying its
therapeutic expertise in RNAi to address significant medical needs, many
of which cannot effectively be addressed with small molecules or
antibodies, the current major classes of drugs. Alnylam is leading the
translation of RNAi as a new class of innovative medicines with
peer-reviewed research efforts published in the world’s
top scientific journals including Nature, Nature Medicine,
and Cell. The company is leveraging these capabilities to build a
broad pipeline of RNAi therapeutics; its most advanced program is in
Phase II human clinical trials for the treatment of respiratory
syncytial virus (RSV) infection. In addition, the company is developing
RNAi therapeutics for the treatment of influenza, hypercholesterolemia,
and liver cancers, among other diseases. The company’s
leadership position in fundamental patents, technology, and know-how
relating to RNAi has enabled it to form major alliances with leading
companies including Medtronic, Novartis, Biogen Idec, and Roche. The
company, founded in 2002, maintains headquarters in Cambridge,
Massachusetts. For more information, visit www.alnylam.com.

About Isis Pharmaceuticals, Inc.

Isis is exploiting its expertise in RNA to discover and develop novel
drugs for its product pipeline and for its partners. The Company has
successfully commercialized the world’s first antisense drug and has 19
drugs in development. Isis’ drug development
programs are focused on treating cardiovascular and metabolic diseases.
Isis’ partners are developing antisense drugs
invented by Isis to treat a wide variety of diseases. Ibis Biosciences,
Inc., Isis’ majority-owned subsidiary, is
developing and commercializing the Ibis T5000™
Biosensor System, a revolutionary system to identify infectious
organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint
venture focused on the discovery, development and commercialization of
microRNA therapeutics. As an innovator in RNA-based drug discovery and
development, Isis is the owner or exclusive licensee of over 1,500
issued patents worldwide. Additional information about Isis is available
at www.isispharm.com.

Alnylam/Isis Forward Looking Statements

This press release includes forward-looking statements regarding the
future therapeutic and commercial potential of Isis’,
Alnylam’s and Regulus’
business plans, technologies and intellectual property related to
microRNA therapeutics being discovered and developed by Regulus,
including statements regarding expectations around the newly formed
relationship between Regulus and GSK. Any statement describing Isis’,
Alnylam’s or Regulus’
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 its 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 Isis, Alnylam or
Regulus, as the case may be. As a result, you are cautioned not to rely
on these forward-looking statements. These and other risks concerning
Isis’, Alnylam’s
and Regulus’ programs are described in
additional detail in Isis’ annual report on
Form 10-K for the year ended December 31, 2007 and in Alnylam’s
annual report on Form 10-K for the year ended December 31, 2007, which
are on file with the SEC. Copies of this and other documents are
available from Isis, Alnylam or Regulus.

About GlaxoSmithKline

GlaxoSmithKline – one of the world’s
leading research-based pharmaceutical and healthcare companies –
is committed to improving the quality of human life by enabling people
to do more, feel better and live longer.

About the II CEDD

The Immuno-Inflammation Centre of Excellence for Drug Discovery is
dedicated to discovering therapies for inflammatory diseases such as
rheumatoid arthritis, inflammatory bowel disease and psoriasis. It is
designed to integrate and better coordinate the progression of
inflammatory disease medicines from therapeutic hypothesis to clinical
proof of concept. It focuses on building an innovative pipeline through
both internal efforts and external alliances with other companies and
research institutions and will focus on ‘virtualizing’ a portion of the
inflammatory diseases pipeline by forming multiple
risk-sharing/reward-sharing alliances.