Idera Pharmaceuticals Announces Positive Top-line Results from Phase 2 Trial of IMO-3100 in Patients with Moderate-to-Severe

  Idera Pharmaceuticals Announces Positive Top-line Results from Phase 2 Trial
  of IMO-3100 in Patients with Moderate-to-Severe Plaque Psoriasis

 TLR antagonist achieves statistically significant improvement in PASI scores
                        after four weeks of treatment

    Reduction in PASI score sustained for up to four weeks post-treatment

Business Wire

CAMBRIDGE, Mass. -- December 19, 2012

Idera Pharmaceuticals (NASDAQ: IDRA) today announced that 48% of patients with
moderate-to-severe plaque psoriasis (12 of 25) treated with IMO-3100, a
selective antagonist of Toll-like Receptors (TLRs) 7 and 9, demonstrated
improvements in Psoriasis Area Severity Index (PASI) scores of 35% to 90% from
baseline at the completion of a randomized, double-blind, placebo-controlled
Phase 2a clinical trial of two dose levels of IMO-3100 administered for four
weeks, with a four-week follow-up period. None of the 12 placebo-treated
patients had improvement in this range; this difference was statistically
significant (p<0.005). The Company believes the results of this trial provide
clinical proof-of-concept for the mechanism of action of selective TLR
inhibition in patients with psoriasis and potentially other autoimmune and
inflammatory disorders.

“The clinical activity of IMO-3100 demonstrated in patients with
moderate-to-severe plaque psoriasis is encouraging, especially given the short
duration of treatment in this study that was designed for initial explorations
of safety and efficacy,” commented Alexa Kimball, M.D., M.P.H., Vice Chair,
Department of Dermatology at Massachusetts General Hospital, Boston, and an
investigator in the trial.

“The achievement of statistically significant PASI reductions with only four
weeks of treatment in a placebo-controlled double-blind trial directly
supports the rationale that the modulation of specific TLRs plays a key role
in the treatment of psoriasis and, potentially, other autoimmune and
inflammatory disorders,” commented James Krueger, M.D., Ph.D., of The
Rockefeller University, New York. “We are excited to see these data, which
demonstrate the translation of targeting a novel mechanism of action into
clinical activity and support further studies of TLR antagonists for the
treatment of psoriasis. Our laboratory is continuing to evaluate the
immunological pathways by which TLR antagonists suppress the signaling
cascades that underlie psoriasis and have the potential to open up a new
approach to disease treatment.”

About the IMO-3100 Phase 2 Trial in Psoriasis

The Phase 2 trial was a randomized, double-blind, placebo-controlled trial of
IMO-3100 in patients with moderate-to-severe plaque psoriasis. In the trial,
44 patients were randomized to receive IMO-3100 monotherapy at 0.16 or 0.32
mg/kg or placebo by subcutaneous injection once weekly for four weeks with
four weeks of follow-up. Assessments of safety were performed throughout the
treatment and follow-up periods. Multiple parameters were monitored to assess
the clinical activity of IMO-3100, including Psoriasis Area Severity Index
(PASI), mean focal psoriasis severity and Physician Global Assessment (PGA)
scores. In addition to the clinical assessments, biopsies of psoriasis plaques
were evaluated for treatment-related changes in epidermal thickness and immune
cell infiltrates consistent with the intended mechanism of action. Patients
were enrolled at eleven sites in the United States.

Top-line clinical results from this trial include:

  *Of the 44 enrolled patients, 40 were clinically evaluable at the end of
    the four-week treatment period and 37 were evaluable following the
    four-week follow up period
  *Treatment at both IMO-3100 dose levels was well tolerated, with no
    treatment-related discontinuations
  *Among evaluable patients, the median PASI scores at treatment initiation
    were 14.9, 16.1, and 12.5 in the 0.16 mg/kg, 0.32 mg/kg, and placebo
    cohorts, respectively
  *A treatment effect was demonstrated in measures of clinical efficacy in
    patients in both IMO-3100 dose cohorts; PASI reductions at both dose
    levels were sustained throughout the four-week follow-up period
  *At the end of the four-week follow-up period, 48% of patients treated with
    either dose of IMO-3100 (12 of 25) demonstrated improvements of 35% to 90%
    from baseline PASI scores compared with 0 of 12 in the placebo cohort;
    this difference was statistically significant (p<0.005)
  *The trial achieved the pre-specified clinical endpoint of reduction in
    PASI scores at the end of treatment in the 0.16 mg/kg dose cohort with
    statistical significance (p<0.02) compared to the placebo cohort, but not
    in the 0.32 mg/kg dose cohort
  *The 0.16 mg/kg cohort also achieved, with statistical significance
    (p<0.02), the pre-specified clinical endpoint of improvement in
    induration, a measure of plaque thickness, at the end of treatment and
    during the follow-up period
  *At the end of the four-week follow-up period, 25% (3 of 12) of patients
    treated with 0.16 mg/kg dose and 31% (4 of 13) with 0.32 mg/kg dose
    achieved PASI 50 or greater, compared to 0 of 12 placebo patients

Skin biopsies were collected at baseline and after completion of treatment to
investigate changes in epidermal thickness and immune cell infiltrates. Change
in epidermal thickness was the primary endpoint for the trial. Placebo treated
patients had a median change in epidermal thickness of +7.7% compared to a
median change of -6.4% among IMO-3100 treated patients; this difference was
not statistically significant. A known limitation of skin biopsies after four
weeks of treatment is that psoriatic plaques do not resolve in a uniform
fashion, and therefore, biopsies may not provide a representative sampling of
lesions (ref: Ann Rheum Dis 2005;64:65-68).

The Company plans to present complete clinical data from this trial at an
upcoming medical meeting.

“We believe this trial in patients with moderate-to-severe plaque psoriasis
provides clinical proof-of-concept for this first-in-class TLR antagonist,
which represents a novel approach to the treatment of autoimmune diseases. We
are very pleased to have observed clinical responses after only four weeks of
treatment,” stated Sudhir Agrawal, D. Phil., Chief Executive Officer of Idera.
“The insights gained from this trial support expansion of our TLR antagonist
program for the treatment of autoimmune diseases. In 2013, we plan to advance
the clinical development of a selective TLR antagonist for the treatment of
moderate-to-severe plaque psoriasis and also for the treatment of lupus.”

About TLRs and Idera's Pipeline

Toll-like Receptors (TLRs) play a key role in inflammation and immunity. Of
the 10 human TLRs identified to date, Idera is developing compounds targeted
to TLRs 3, 7, 8 and 9, which are expressed in different cells and serve unique
functions. Using its chemistry-based approach, Idera has created novel drug
candidates that modulate immune responses through either activation or
inhibition of specific TLRs. Inhibition of specific TLRs may be useful in
treating autoimmune disorders, such as systemic lupus erythematosus (SLE),
psoriasis and rheumatoid arthritis, by blocking the induction of multiple
cytokines and signaling pathways. Idera's clinical candidates for application
in autoimmune diseases are IMO-3100, an antagonist of TLR7 and TLR9, and
IMO-8400, an antagonist of TLRs 7, 8 and 9.

A characteristic of autoimmune diseases such as SLE and psoriasis is the
production of immune complexes with self-nucleic acids. These abnormal immune
complexes activate TLRs 7, 8 and 9 and induce multiple cytokines that cause
further damage to the body's own tissues and organs, thereby releasing more
self-nucleic acids. Thus, a pathologic amplification cycle is established,
promoting disease maintenance and progression. In preclinical models of
several autoimmune diseases, IMO-3100 and IMO-8400 inhibited TLR-mediated
immune responses, interrupted the cycle of disease maintenance and progression
through decreases in Th1, Th17 and inflammasome pathways, and led to
improvements in multiple measures of disease.

About IMO-3100

IMO-3100, an antagonist of TLR7 and TLR9, is a lead drug candidate in
development to treat autoimmune diseases, including psoriasis. In preclinical
mouse models of psoriasis, IMO-3100 exerted therapeutic activity by inhibiting
disease-associated gene expression and cytokines, such as IL-6, IL-22, IL-17,
IL-23, NLRP3 and IL-1β, and proteins in the skin such as S100A7, DEFB4 and
LL37. In addition, histological evaluation showed that the psoriatic lesions
in IMO-3100-treated animals had reduced epidermal thickness and decreased
lymphocyte infiltration compared to control mice.

About Psoriasis

Psoriasis is a systemic immune-mediated disorder, characterized by
inflammatory skin and joint manifestations. The most common form, plaque
psoriasis, appears as raised, red patches covered with a silvery white buildup
of dead skin cells. Psoriasis can occur on any part of the body and is
associated with other serious health conditions, such as diabetes, heart
disease and depression.

Psoriasis is the most prevalent autoimmune disease in the U.S., according to
the National Psoriasis Foundation, affecting as many as 7.5 million Americans.

About Idera Pharmaceuticals, Inc.

Idera Pharmaceuticals applies its proprietary Toll-like receptor (TLR) drug
discovery platform to create immunomodulatory drug candidates and has a
clinical development program in autoimmune diseases. Additionally, Idera has a
collaboration with Merck & Co. for the use of TLR-targeted candidates as
vaccine adjuvants for cancer, infectious diseases and Alzheimer’s disease. The
Company is also exploring its gene-silencing oligonucleotide (GSO) technology
for the purpose of inhibiting the expression of disease-promoting genes. For
more information, visit http://www.iderapharma.com.

Idera Forward Looking Statements

This press release contains forward-looking statements concerning Idera
Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For
this purpose, any statements contained herein that are not statements of
historical fact may be deemed to be forward-looking statements. Without
limiting the foregoing, the words "believes," "anticipates," "plans,"
"expects," "estimates," "intends," "should," "could," "will," "may," and
similar expressions are intended to identify forward-looking statements. There
are a number of important factors that could cause Idera's actual results to
differ materially from those indicated by such forward-looking statements,
including whether Idera’s cash resources will be sufficient to fund the
Company’s continuing operations and the further development of the Company’s
autoimmune disease program; whether results obtained in preclinical studies
and early clinical trials, such as the results from the Phase 2 trial and the
preclinical studies referred to in this release, will be indicative of results
obtained in future clinical trials; whether products based on Idera's
technology will advance into or through the clinical trial process on a timely
basis or at all and receive approval from the United States Food and Drug
Administration or equivalent foreign regulatory agencies; whether, if the
Company's products receive approval, they will be successfully distributed and
marketed; whether the Company will be able to license any of its TLR target
candidates on a timely basis or at all; whether the Company's collaboration
with Merck & Co, Inc., will be successful; whether the patents and patent
applications owned or licensed by the Company will protect the Company's
technology and prevent others from infringing it; and such other important
factors as are set forth under the caption "Risk Factors" in Idera's Quarterly
Report on Form 10-Q for the quarter ended September 30, 2012 which important
factors are incorporated herein by reference. Idera disclaims any intention or
obligation to update any forward-looking statements.

Contact:

Idera Pharmaceuticals, Inc.
Lou Arcudi, 617-679-5517
larcudi@iderapharma.com