Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage
biopharmaceutical company developing toll-like receptor and RNA
therapeutics for patients with cancer and rare diseases, is
reporting translational data supporting the mechanism of action of
intratumoral IMO-2125, a Toll-like receptor (TLR) 9 agonist from
the ongoing Phase 1 dose escalating clinical trial. In this
trial, IMO-2125 is being evaluated in combination with ipilimumab
for treatment of patients with metastatic melanoma with disease
that is refractory to anti-PD-1 inhibitors, and have minimal
options and low expectation of clinical response with ipilimumab
treatment alone. Taken together, the previously reported early
clinical responses and the supporting mechanism of action
translational data being presented today, indicate that
intratumoral IMO-2125 is a potent agent for the stimulation of the
tumor microenvironment.
In the oral presentation at the 2016 Society for Immunotherapy
of Cancer Annual Meeting (SITC), entitled “Reactivating the
anti-tumor immune response by targeting innate and adaptive
immunity in a phase I/II study of intratumoral IMO-2125 in
combination with systemic ipilimumab in patients with anti-PD-1
refractory metastatic melanoma,” Cara Haymaker, Ph.D., from the
University of Texas, MD Anderson Cancer Center, presented an
overview of the modulation of the tumor microenvironment through
the unique mechanism of action of intratumoral IMO-2125 and
provided an update on the initial findings of the translational
data through the first cohorts of the trial. Immunological
analysis of the biopsy taken from the lesion injected with IMO-2125
showed rapid dendritic cell maturation which is a critical first
step in the induction of the immune cascade within the tumor
microenvironment. During the treatment period, T-cell
expansion and activation and importantly, immune infiltration was
observed in the biopsied distant lesions of the responding
patients, demonstrating the abscopal effect.
From a clinical perspective, through all dosing cohorts tested
to date, no dose-limiting toxicity has been seen. Preliminary
clinical activity is also encouraging in this population with
disease that is refractory to PD-1 inhibitors as 3 responses
(including one CR) have already been recorded. The trial
continues to dose escalate and enrollment into the planned
anti-PD-1 inhibitor combination arm has also commenced.
“We hypothesized that the intratumoral injection of IMO-2125
into a single tumor lesion would stimulate dendritic cells to
produce interferon and the downstream immune cascade in the tumor
microenvironment, resulting in the recruitment and activation of
tumor-killing T-cells in both the injected and non-injected
tumors,” said Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical
Officer. “When combined with a systemic checkpoint inhibitor,
this change in the tumor microenvironment was expected to affect
tumor responses in both injected and distant tumors. Today
Dr. Haymaker presented analyses of serial biopsies from the tumors
of patients with anti-PD-1 refractory melanoma in our ongoing phase
1 dose escalation trial of intratumoral IMO-2125 which clearly
demonstrated these beneficial changes in the tumor
microenvironment, essentially turning “cold” tumors “hot” in
responding patients. We are thrilled to see what we believe to be,
the clear translation of our hypothesis in patients.
Moreover, in three patients the investigator has reported
substantial tumor shrinkage with 2 partial and one complete
response.”
A copy of the slides from today’s presentation as well as a copy
of a related poster presentation are currently available on Idera’s
corporate website at
http://www.iderapharma.com/our-approach/key-publications/.
These early results are from the phase 1 portion of study
IMO-2125-204 (NCT02644967) in which cohorts of patients with
metastatic melanoma unresponsive to PD-1 inhibitor therapy are
being administered escalating doses of IMO-2125 ranging from 4
mg/kg through 32 mg/kg. IMO-2125 is injected intra-tumorally into a
designated tumor lesion together with a standard dosing regimen of
ipilimumab. The trial has recently been amended to also study the
combination of IMO-2125 and pembrolizumab given intravenously.
Following determination of the recommended phase 2 doses (RP2D)
additional patients will be treated in an expansion phase 2 portion
of the study. The primary objective of the phase 1 portion of the
trial is to characterize the safety and determine a RP2D of
IMO-2125 when administered intra-tumorally in combination with
ipilimumab or pembrolizumab. The primary objective of the
phase 2 portion is to assess the clinical activity of IMO-2125 in
each combination at the respective RP2Ds. Assessment will be
based on the immune-related response criteria (irRC) and
additionally the traditional RECIST criteria. Serial biopsies
are being taken of selected injected and non-injected tumor lesions
to assess immune changes and correlate with clinical response
assessments. The trial will enroll approximately 60
patients. The study is being conducted at MD Anderson and is
being led by Adi Diab, MD, Assistant Professor, Department of
Melanoma Medical Oncology, Division of Cancer Medicine, MD Anderson
as part of a strategic research alliance announced by Idera and MD
Anderson in 2015.
Additionally at SITC, on November 9th, Idera’s Oncology Lead,
Mark Cornfeld, M.D., M.P.H., presented an overview of IMO-2125’s
unique mechanism of action in an oral presentation, entitled
“IMO-2125, An Investigational Intratumoral Toll-Like Receptor 9
Agonist, Modulates the Tumor Microenvironment to Enhance Anti-Tumor
Immunity” during a session focused on New Clinical Agents in
Development. A copy of the slides from this presentation is
currently available on Idera’s corporate website at
http://www.iderapharma.com/our-approach/key-publications/.
About Toll-like Receptors and Idera's Immuno-Oncology
Research Program
Toll-like receptors (TLRs) play a central role in the innate
immune system, the body's first line of defense against invading
pathogens, as well as damaged or dysfunctional cells including
cancer cells. The innate immune system is also involved in
activating the adaptive immune system, which marshals highly
specific immune responses to target pathogens or tissue. Cancer
cells may exploit regulatory checkpoint pathways to avoid being
recognized by the immune system, thereby shielding the tumor from
immune attack. Checkpoint inhibitors such as agents targeting CTLA4
or programmed cell death protein 1 (PD1) are designed to enable the
immune system to recognize tumor cells. In this setting,
intra-tumoral TLR9 agonist administration may increase the
tumor-infiltrating lymphocytes (TILs), and thereby potentiate
anti-cancer activity of checkpoint inhibitors in the injected tumor
as well as systemically.
Idera’s TLR9 agonists, IMO-2125 and IMO-2055, have been created
using the company's proprietary chemistry-based discovery
platform. IMO-2125 has been shown in various scientific
presentations and publications to activate dendritic cells and
induce interferon. Idera selected IMO-2125 to advance into clinical
development in combination with checkpoint inhibitors based on this
immunological profile. In previously completed clinical
trials, subcutaneous administration of IMO-2125 was generally well
tolerated in about 80 patients with hepatitis C. Idera has
conducted further preclinical research evaluating the potential of
IMO-2125 to enhance the anti-tumor activity of other checkpoint
inhibitors in cancer immunotherapy with data being presented at
several medical conferences during the past twelve months.
The posters from these presentations can be found at
http://www.iderapharma.com/our-approach/key-publications.
About Metastatic MelanomaMelanoma is a type of
skin cancer that begins in a type of skin cell called
melanocytes. As is the case in many forms of cancer, melanoma
becomes more difficult to treat once the disease has spread beyond
the skin to other parts of the body such as by through the
lymphatic system (metastatic disease). Melanoma accounts for
only one percent of skin cancer cases, but causes a large majority
of skin cancer deaths. The American Cancer Society estimates
that in 2016, there will be 76,380 new cases of melanoma in the
U.S., and about 10,130 will die of this disease.
About Idera
Pharmaceuticals
Idera Pharmaceuticals is a clinical-stage biopharmaceutical company
developing novel nucleic acid-based therapies for the treatment of
certain cancers and rare diseases. Idera’s proprietary technology
involves designing synthetic oligonucleotide-based drug candidates
to modulate the activity of specific TLRs. In addition to its TLR
programs, Idera has used its proprietary knowledge to create a
third generation antisense technology platform which inhibits the
production of disease-associated proteins by targeting RNA. To
learn more about Idera, visit www.iderapharma.com.
Forward Looking StatementsThis press release
contains forward-looking statements within the meaning of Section
27A of the Securities Act of 1933, as amended, and Section 21E of
the Securities Exchange Act of 1934, as amended. All statements,
other than statements of historical fact, included or incorporated
in this press release, including statements regarding the Company's
strategy, future operations, collaborations, intellectual property,
cash resources, financial position, future revenues, projected
costs, prospects, plans, and objectives of management, are
forward-looking statements. The words "believes," "anticipates,"
"estimates," "plans," "expects," "intends," "may," "could,"
"should," "potential," "likely," "projects," "continue," "will,"
and "would" and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. Idera cannot guarantee
that it will actually achieve the plans, intentions or expectations
disclosed in its forward-looking statements and you should not
place undue reliance on the Company's forward-looking statements.
There are a number of important factors that could cause Idera's
actual results to differ materially from those indicated or implied
by its forward-looking statements. Factors that may cause such a
difference include: whether interim results from a clinical trial,
such as preliminary results reported in this release, will be
predictive of the final results of the trial, whether results
obtained in preclinical studies and clinical trials such as the
preclinical data described in this release will be indicative of
the results that will be generated in future clinical trials,
including in clinical trials in different disease indications;
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; and such other important
factors as are set forth under the caption "Risk Factors" in the
Company's Annual Report and on Form 10-Q for the period ended
September 30, 2016. Although Idera may elect to do so at some point
in the future, the Company does not assume any obligation to update
any forward-looking statements and it disclaims any intention or
obligation to update or revise any forward-looking statement,
whether as a result of new information, future events or
otherwise.
Investor and Media Contact
Robert Doody
Vice President, Investor Relations and Corporate Communications
Office: 617-679-5515
Mobile: 484‐639‐7235
rdoody@iderapharma.com
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